Dapivirine (DPV)

Associated long-acting platforms

Intra-vaginal ring

Administration route

Topical (Vaginal)

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

No delivery device

Scale-up prospects

DPV is manufactured commercially through a well-defined synthetic chemical process and undergoes a micronisation procedure to improve drug dispersion within the silicon intravaginal ring. The current DPV ring formulation (Ring-004) contains 25mg of micronised drug product and is produced with NuSil™ DDU-4870 silicone elastomer using addition-curing to prevent the formation of undesirable volatile alcohol by-products. This formulation provides high pharmacokinetic exposure with low overall manufacturing costs. Novel additive manufacturing techniques (e.g. APF) could provide new formulations.

Tentative equipment list for manufacturing

For ring manufacture: Injection molding machine, mixer, automated inspection and packaging machines.

Manufacturing

Manufacturing is a non-standard four stage workflow process: (1) preparation of the master batch, (2) pre-mix formation, (3) ring construction using injection addition-curing, and (4) packaging/inspection. For DPV Compound: stability testing indicates that the chemical compound can be stored for up to 6 months at 40ºC and 96 months at 25ºC in the pre-specified commercial packaging. DPV is photo-stable. For Finished Ring Product: stability testing shows that the product can be stored for 48 months at 30ºC. The DPV ring product is photosensitive and should be stored away from light sources.

Specific analytical instrument required for characterization of formulation

For DPV Compound: HPLC (determine chemical purity), GC (residual solvents), laser diffraction (determine particle size), Karl Fischer titration (determine water content) and FT-IR & DSC (chemical identification). For Finished Ring Product: HPLC (determine dissolution, content uniformity and degradation products), compression testing machine (determine tensile and compression properties).

Pharmacokinetic Study of the Dapivirine Vaginal Ring in Lactating Women

Identifier

NCT02808949

Link

https://clinicaltrials.gov/study/NCT02808949

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Phase 1 PK Study of the Dapivirine Vaginal Ring in Lactating Women.

Purpose

Pharmacokinetic Study of the Dapivirine Vaginal Ring in Lactating Women

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-02-01

Anticipated Date of Last Follow-up
2018-03-12

Estimated Primary Completion Date
2016-06-22

Estimated Completion Date
2016-06-22

Actual Primary Completion Date
2018-03-13

Actual Completion Date
2018-03-03

Studied populations

Age Cohort

• Adults

Genders

• Female

Accepts pregnant individuals
Yes

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: Women must meet all of the following criteria (by self-report, unless otherwise indicated) to be eligible for inclusion in the study: 1. Age 18 or older at screening as verified per site SOP 2. Per participant report, at least 6 weeks postpartum at Enrollment 3. Willing and able to provide written informed consent to be screened for and take part in the study 4. Willing and able to provide adequate locator information, as defined in site SOP 5. Willing and able to communicate in spoken and written English 6. HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II and willing to receive HIV test results Note: HIV-1/2 screening may be omitted at Enrollment if the time between Screening and Enrollment is \< 30 days 7. Prior to Enrollment,

Health status

Study type

Interventional (clinical trial)

Enrollment

16

Allocation

Non-randomized

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 035

Identifier

NCT02858024

Link

https://clinicaltrials.gov/ct2/show/NCT02858024

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the effects of tampon use and menses on the pharmacokinetics of Dapivirine vaginal ring-004 in HIV-uninfected women.

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Not provided

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-01-12

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2016-04-16

Actual Completion Date
2016-04-16

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged between 18 and ≤ 40 years.

Health status

Study type

Interventional (clinical trial)

Enrollment

16

Allocation

Randomized

Intervention model

Cross-over assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 054

Identifier

NCT05416021

Link

https://clinicaltrials.gov/ct2/show/NCT05416021

Phase

Phase I

Status

Active, not recruiting

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Compare the relative bioavailability in plasma and vaginal fluid of the 25mg Dapivirine vaginal ring-004 and 100 mg Dapivirine vaginal ring-008 in HIV-uninfected women.

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2022-08-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
2024-04-01

Estimated Completion Date
2024-04-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged 18-45 inclusive.

Health status

Study type

Interventional (clinical trial)

Enrollment

110

Allocation

Randomized

Intervention model

Cross-over assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

MTN-036/IPM-047

Identifier

NCT03234400

Link

https://clinicaltrials.gov/ct2/show/NCT03234400

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the safety and pharmacokinetics of extended duration Dapivirine vaginal rings.

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2017-12-04

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2018-10-23

Actual Completion Date
2019-01-23

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged 18-45 inclusive.

Health status

Study type

Interventional (clinical trial)

Enrollment

49

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Single blind masking

Masking description

Single (Participant)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

DREAM (IPM 032)

Identifier

NCT02862171

Link

https://clinicaltrials.gov/study/NCT02862171

Phase

Phase III

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

A follow-on, open label trial to assess continued safety of and adherence to the Dapivirine(25mg) vaginal ring-004 in healthy, HIV-negative women

Purpose

To Assess Continued Safety of and Adherence to the Dapivirine (25 mg) Vaginal Ring-004 in Healthy, HIV-negative Women

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2016-07-12

Anticipated Date of Last Follow-up
2022-10-24

Estimated Primary Completion Date
2016-08-10

Estimated Completion Date
2016-08-10

Actual Primary Completion Date
2022-10-25

Actual Completion Date
2019-01-11

Studied populations

Age Cohort

• Adults

Genders

• Female
• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: Women must meet all the following criteria to be eligible to enrol in the trial: 1. Previously enrolled in the IPM 027 trial 2. Available for all visits and consent to follow all procedures scheduled for the trial 3. Using an effective method of contraception at the Enrolment Visit, and intending to use an effective contraceptive method for the duration of trial participation, unless post-menopausal with no history of menses for one year prior to screening 4. HIV-negative as determined by the HIV algorithm applied at Screening/Pre- Enrolment 5. Willing to refrain from participation in another research trial using drugs, vaccines, medical devices and microbicides for the duration of the IPM 032 trial 6. Willing to provide adequate locator information for trial retentio

Health status

Study type

Interventional (clinical trial)

Enrollment

941

Allocation

Non-randomized

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

MTN-024/IPM031

Identifier

NCT02010593

Link

https://clinicaltrials.gov/ct2/show/NCT02010593

Phase

Phase II

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the safety of the Dapivirine vaginal ring when administered once every 28 days for twelve weeks in postmenopausal women.

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2013-12-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2015-04-01

Actual Completion Date
2015-04-01

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged 45-65 inclusive.

Health status

Study type

Interventional (clinical trial)

Enrollment

96

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Double (Participant, Investigator)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

ASPIRE (MTN-020)

Identifier

NCT01617096

Link

https://clinicaltrials.gov/study/NCT01617096

Phase

Phase III

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Phase 3 Safety and Effectiveness Trial of Dapivirine Vaginal Ring for Prevention of HIV-1 in Women This is a double-blind, randomised, placebo-controlled study to assess the safety and efficacy of a silicone elastomer vaginal matrix ring.

Purpose

Phase 3 Safety and Effectiveness Trial of Dapivirine Vaginal Ring for Prevention of HIV-1 in Women

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2012-07-24

Anticipated Date of Last Follow-up
2022-12-19

Estimated Primary Completion Date
2012-06-12

Estimated Completion Date
2012-06-12

Actual Primary Completion Date
2022-12-21

Actual Completion Date
2015-12-01

Studied populations

Age Cohort

• Adults

Genders

• Female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: * Age 18 through 45 years (inclusive) at screening, verified per site SOPs; within this range, sites may restrict the upper age limit per site SOPs, to target women at high risk of HIV infection * Able and willing to provide written informed consent to be screened for and to take part in the study * Able and willing to provide adequate locator information, as defined in site SOPs * HIV-uninfected based on testing performed by study staff at screening and enrollment (per applicable algorithm in Appendix II) * Per participant report, sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening * Using an effective method of contraception at enrollment, and intending to use an effective method for the duration of study participat

Health status

Study type

Interventional (clinical trial)

Enrollment

2629

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

MTN-034

Identifier

NCT03593655

Link

https://clinicaltrials.gov/ct2/show/NCT03593655

Phase

Phase II

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

Not provided

Purpose

Evaluate the adherence and safety of a Dapivirine vaginal ring with oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in adolescent and young adult females.

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-01-14

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2021-09-09

Actual Completion Date
2021-09-09

Studied populations

Age Cohort

• Adolescents
• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged 16-21 inclusive.

Health status

Study type

Interventional (clinical trial)

Enrollment

247

Allocation

Randomized

Intervention model

Cross-over assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

HOPE (MTN-025)

Identifier

NCT02858037

Link

https://clinicaltrials.gov/study/NCT02858037

Phase

Phase III

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

HIV Open-label Prevention Extension (HOPE) to Assess the Continued Safety of and Adherence to a Monthly Vaginal Ring Containing Dapivirine in Women

Purpose

Trial to Assess the Continued Safety of and Adherence to a Vaginal Ring Containing Dapivirine in Women

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2016-07-18

Anticipated Date of Last Follow-up
2022-10-24

Estimated Primary Completion Date
2016-08-08

Estimated Completion Date
2016-08-08

Actual Primary Completion Date
2022-10-25

Actual Completion Date
2018-10-10

Studied populations

Age Cohort

• Adults

Genders

• Female
• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: Women must meet all of the following criteria to be eligible for inclusion in the study 1. Previously enrolled in MTN-020 (ASPIRE) 2. Able and willing to provide written informed consent to be screened for and to take part in the study 3. Able and willing to provide adequate locator information, as defined in site SOPs 4. HIV-uninfected based on testing performed by study staff at Screening and Enrollment 5. Using an effective method of contraception at Enrollment, and intending to use an effective method for the duration of study participation; effective methods include hormonal methods (except contraceptive ring); intrauterine contraceptive device (IUCD); and sterilization (of participant, as defined in site SOPs) 6. At Screening and Enrollment, agrees not to partic

Health status

Study type

Interventional (clinical trial)

Enrollment

1456

Allocation

Non-randomized

Intervention model

Single group assignment

Intervention model description

Participants will receive a silicone elastomer vaginal matrix ring containing 25 mg of dapivirine to be replaced each month for a total period of 12 months of use.

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

DELIVER (MTN-042)

Identifier

NCT03965923

Link

https://clinicaltrials.gov/study/NCT03965923

Phase

Phase III

Status

Active, not recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the maternal and infant safety of the dapivirine (DPV) monthly vaginal ring (VR) and daily oral Truvada in HIV-uninfected pregnant women and their infants.

Purpose

Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2020-01-09

Anticipated Date of Last Follow-up
2023-02-01

Estimated Primary Completion Date
2019-05-29

Estimated Completion Date
2019-05-29

Actual Primary Completion Date
2023-02-02

Actual Completion Date
2024-06-30

Studied populations

Age Cohort

• Adults

Genders

• Female
• Cisgender female

Accepts pregnant individuals
Yes

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: * Age 18 through 40 years (inclusive) at Enrollment, verified per site standard operating procedures (SOPs). * At Enrollment, evidence of a viable, intrauterine, singleton pregnancy with sonographic confirmation, including for gestational age assessment. * Note: If adequate (per judgment of Investigator of Record \[IoR\]/designee) sonographic results are not available from medical records at Screening, an ultrasound must be performed and results be available for review at Enrollment for all Cohorts. The ultrasound should be performed no later than the 36th week of gestation for Cohort 1 or the 28th week of gestation for Cohort 2. * At Enrollment, pregnancy within gestational age limits of the currently enrolling cohort (per the study protocol). * HIV-uninfected base

Health status

Study type

Interventional (clinical trial)

Enrollment

859

Allocation

Randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 024

Identifier

NCT02920827

Link

https://clinicaltrials.gov/ct2/show/NCT02920827

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the tolerability and safety of the dapivirine ring as compared to a placebo ring when inserted for four weeks in HIV-uninfected women.

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2009-08-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2010-04-01

Actual Completion Date
2010-04-01

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged 18-40 years inclusive.

Health status

Study type

Interventional (clinical trial)

Enrollment

16

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Double (Participant, Investigator)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

Ring Study (IPM 027)

Identifier

NCT01539226

Link

https://clinicaltrials.gov/study/NCT01539226

Phase

Phase III

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

The Ring study was a Phase 3, double-blind, randomised, placebo-controlled study to assess the safety and efficacy of a silicone elastomer monthly vaginal matrix ring.

Purpose

Safety and Efficacy Trial of a Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2012-03-27

Anticipated Date of Last Follow-up
2022-09-26

Estimated Primary Completion Date
2012-02-27

Estimated Completion Date
2012-02-27

Actual Primary Completion Date
2022-10-19

Actual Completion Date
2016-12-13

Studied populations

Age Cohort

• Adults

Genders

• Female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: * Women \> 18 and \< 45 years of age, at screening, who can provide informed consent; * Available for all visits and consent to follow all procedures scheduled for the trial; * Self-reported sexually active (defined as an average of at least one penetrative penile-vaginal coital act per month for the last 3 months prior to screening); * HIV-negative as determined by the HIV algorithm applied at screening and enrolment; * On a stable form of contraception as defined within section 5.4 and willing to continue on stable contraception for the duration of the clinical trial, unless post-menopausal or surgically sterilised; * Asymptomatic for genital infections at the time of enrolment (if a woman is diagnosed with any clinically significant curable STI, she must have initia

Health status

Study type

Interventional (clinical trial)

Enrollment

1959

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

MTN-023/IPM 030

Identifier

NCT02028338

Link

https://clinicaltrials.gov/ct2/show/NCT02028338

Phase

Phase II

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evalute the safety of a 25mg dapivirine vaginal ring in HIV-uninfected adolescent females, when inserted once every 28 days for 24-weeks.

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2014-07-27

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2016-07-05

Actual Completion Date
2018-06-08

Studied populations

Age Cohort

• Adolescents

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Unspecified

Comments about the studied populations

Participants aged 15-17 inclusive at enrollment.

Health status

Study type

Interventional (clinical trial)

Enrollment

96

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Quadruple-blind masking

Masking description

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

A Safety Study of Dapivirine Vaginal Ring in Africa

Identifier

NCT01071174

Link

https://clinicaltrials.gov/study/NCT01071174

Phase

Phase I/II

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

This is a double-blind, randomized, placebo-controlled Phase I/II study to assess the safety of a silicone elastomer vaginal ring containing 25mg dapivirine.

Purpose

A Safety Study of Dapivirine Vaginal Ring in Africa

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2010-04-01

Anticipated Date of Last Follow-up
2011-08-01

Estimated Primary Completion Date
2010-02-19

Estimated Completion Date
2010-02-19

Actual Primary Completion Date
2011-08-02

Actual Completion Date
2011-07-01

Studied populations

Age Cohort

• Adults

Genders

• Female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: * Women between 18 and 40 years of age inclusive who can provide informed consent * Available for all visits and consent to follow all procedures scheduled for the study * Healthy and self-reported sexually active * HIV-negative * On a stable form of contraception and willing to continue OR have undergone surgical sterilization at least 3 months prior to enrollment * In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle defined as having a minimum of 21 days and a maximum of 35 days between menses * Upon pelvic/speculum examination and colposcopy at the time of enrolment, the cervix and vagina appear normal as determined by the investigator * Asymptomatic for genital infections at the time of enrolment * Willing to refrain from

Health status

Study type

Interventional (clinical trial)

Enrollment

280

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Triple-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 034

Identifier

NCT01952561

Link

https://clinicaltrials.gov/ct2/show/NCT01952561

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the blood and vaginal pharmacokinetics of a 25mg Dapivirine vaginal ring worn for 1, 2, 4, 8 or 12 months.

Interventions

Intervention 1

Countries

Not provided

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2013-11-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2014-03-01

Actual Completion Date
2014-05-01

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women between 18-40 years of age.

Health status

Study type

Interventional (clinical trial)

Enrollment

40

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 009B

Identifier

NCT01337583

Link

https://clinicaltrials.gov/ct2/show/NCT01337583

Phase

Phase III

Status

Withdrawn

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the efficacy and safety of a Dapivirine vaginal matrix ring for HIV-1 PrEP in women.

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2011-07-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2014-07-01

Actual Completion Date
2014-07-01

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged between 18-40 years.

Health status

Study type

Interventional (clinical trial)

Enrollment

Not provided

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Double (Participant, Investigator)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 018

Identifier

NCT00469768

Link

https://clinicaltrials.gov/ct2/show/NCT00469768

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the pharmacokinetics and safety of a 25 mg of Dapivirine intravaginal ring in HIV-uninfected women to determine the release of Dapivirine from the reservoir and matrix.

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2007-05-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2007-08-01

Actual Completion Date
2007-08-01

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged between 18-35 years.

Health status

Study type

Interventional (clinical trial)

Enrollment

24

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Double (Participant, Investigator)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 013

Identifier

NCT01144676

Link

https://clinicaltrials.gov/ct2/show/NCT01144676

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the delivery of dapivirine from matrix intravaginal rings to assess the safety in comparison to placebo intravaginal rings in HIV-uninfected sexually active women.

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2010-04-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2010-09-01

Actual Completion Date
2010-09-01

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged between 18-40 years.

Health status

Study type

Interventional (clinical trial)

Enrollment

45

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Double (Participant, Investigator)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 001

Identifier

NCT00700284

Link

https://clinicaltrials.gov/ct2/show/NCT00700284

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the feasibility, safety and tolerability of utilising a vaginal ring delivery system to administer TMC120 (dapivirine).

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2004-10-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2005-01-01

Actual Completion Date
2005-01-01

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged between 18-50 years.

Health status

Study type

Interventional (clinical trial)

Enrollment

12

Allocation

Non-randomized

Intervention model

Cross-over assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

IPM 008

Identifier

NCT00332995

Link

https://clinicaltrials.gov/ct2/show/NCT00332995

Phase

Phase I

Status

Completed

Sponsor

International Partnership for Microbicides, Inc.

More details

Not provided

Purpose

Evaluate the systemic availability, safety and tolerability of a vaginal ring for the delivery of TMC120 (dapivirine).

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2005-07-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2005-08-01

Actual Completion Date
2005-08-01

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Women aged 18-50 years.

Health status

Study type

Interventional (clinical trial)

Enrollment

13

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

Proprietary excipients used

DDU-4870 is a silicon elastomer product manufactured by NuSil™ Technology Inc. (Carpinteria, CA, USA). In 2016, NuSil Technology, Inc. merged with Avantor.

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

The novel excipient DDU-4870 is used in the final Ring-004 product formulation. DDU-4870 is contained and packaged within food-grade certified polyethylene pails, which have no effect on excipient quality. At room temperature (25ºC) DDU-4870 is estimated to maintain chemical stability for 12 months.

Residual solvents used

No residual solvent used

Compound patent families

Publications

Welsh, N. R., Malcolm, R. K., Devlin, B., & Boyd, P. (2019). Dapivirine-releasing vaginal rings produced by plastic freeforming additive manufacturing. International Journal of Pharmaceutics. https://doi.org/10.1016/j.ijpharm.2019.118725

Here we report the first use of an additive manufacturing (AM) technique based on high pressure material jetting of molten thermoplastic for the fabrication of dapivirine (DPV) loaded vaginal rings (VRs). The VRs are compared to those produced conventionally using injection molding (IM). VRs (outer diameter 54.0 mm, cross-sectional diameter 4.0 mm) were manufactured by either injection molding or Arburg Plastic Freeforming (APF) - a proprietary droplet deposition modelling (DDM) process, using medical grade thermoplastic polyurethanes (TPUs) loaded with 10% w/w DPV. This unique DDM process was used to produce rings of 100, 50 and 10% matrix infill density. DDM printed VRs with 10% density (57-62 mg drug load) exhibited up to seven-fold increase in DPV release compared to injection molded rings containing 190-194 mg DPV. This work has shown that DDM using the APF technique can be used to manufacture drug delivery devices of varying geometries, densities and surface areas to give precise levels of control over the drug release kinetics. This work presents a new opportunity to increase the release of poorly watersoluble compounds or to achieve desired dosing levels using lower drug loadings than those required using conventional thermoplastic processing techniques.

Malcolm RK, Woolfson AD, Toner CF, Morrow RJ, McCullagh SD. Long-term, controlled release of the HIV microbicide TMC120 from silicone elastomer vaginal rings. J Antimicrob Chemother. 2005 Nov;56(5):954-6. www.doi.org/10.1093/jac/dki326. Epub 2005 Sep 9. PMID: 16155060.

Objectives: The feasibility of providing prolonged and controlled release of the experimental non-nucleoside reverse transcriptase inhibitor TMC120 from a silicone vaginal ring in quantities sufficient to maintain a vaginal concentration offering protection against heterosexual HIV transmission was investigated.

Methods: Core-type, silicone elastomer vaginal rings containing TMC120 were manufactured, and in vitro release studies performed under sink conditions. The experimental release data, as determined by HPLC, were correlated with estimates of vaginal TMC120 concentrations required to inhibit HIV replication.

Results: Continuous, zero-order release of TMC120 from core-type vaginal rings was observed in vitro over a 71 day period, equivalent to 136 μg/day. The release rate is predicted to maintain vaginal concentrations of the antiretroviral in the range of several orders of magnitude in excess of reported HIV inhibitory concentration values.

Conclusions: Continuous and prolonged zero-order release of TMC120 from a silicone vaginal ring device at quantities predicted to prevent HIV infection was observed.

Diarylaniline Derivatives as a Distinct Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors. Bingjie Qin, Xingkai Jiang, Hong Lu, Xingtao Tian, Florent Barbault, Li Huang, Keduo Qian, Chin-Ho Chen, Rong Huang, Shibo Jiang, Kuo-Hsiung Lee, and Lan Xie. Journal of Medicinal Chemistry, 2010, 53 (13), 4906-4916. www.doi.org/10.1021/jm1002952

By using structure-based drug design and isosteric replacement, diarylaniline and 1,5-diarylbenzene-1,2-diamine derivatives were synthesized and evaluated against wild type HIV-1 and drug-resistant viral strains, resulting in the discovery of diarylaniline derivatives as a distinct class of next-generation HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) agents. The most promising compound 37 showed significant EC50 values of 0.003−0.032 μM against HIV-1 wild-type strains and of 0.005−0.604 μM against several drug-resistant strains. Current results also revealed important structure−activity relationship (SAR) conclusions for diarylanilines and strongly support our hypothesis that an NH2 group on the central benzene ring ortho to the aniline moiety is crucial for interaction with K101 of the NNRTI binding site in HIV-1 RT, likely by forming H-bonds with K101. Furthermore, molecular modeling studies with molecular mechanism/general Born surface area (MM/GBSA) technology demonstrated the rationality of our hypothesis.

Additional documents

No documents were uploaded

Useful links

• Dapivirine Vaginal Ring 25 mg: Opinion on medicine for use outside EU

• WHO recommends the dapivirine vaginal ring as a new choice for HIV prevention for women

• Dapivirine Vaginal Ring for HIV Prevention

• Pharmacokinetics of Dapivirine Transfer into Blood Plasma, Breast Milk, and Cervicovaginal Fluid of Lactating Women Using the Dapivirine Vaginal Ring

• Phase 1 pharmacokinetics and safety study of extended duration dapivirine vaginal rings in the United States

• Users' Preferred Characteristics of Vaginal Rings for HIV Prevention: A Qualitative Analysis of Two Phase I Trials

• Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM): an open-label, extension study

• Acceptability of the Dapivirine Vaginal Ring in Postmenopausal US Women

• Phase 2a Safety, Pharmacokinetics, and Acceptability of Dapivirine Vaginal Rings in US Postmenopausal Women

• Patterns of Adherence to a Dapivirine Vaginal Ring for HIV-1 Prevention Among South African Women in a Phase III Randomized Controlled Trial

• Experiences with simultaneous use of contraception and the vaginal ring for HIV prevention in sub-Saharan Africa

• Acceptability of the Dapivirine Vaginal Ring for HIV-1 Prevention and Association with Adherence in a Phase III Trial

• Risk of HIV-1 acquisition among South African women using a variety of contraceptive methods in a prospective study

• Acquisition of Sexually Transmitted Infections among Women Using a Variety of Contraceptive Options: A prospective Study among High-risk African Women

• Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

• Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE

• Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women

• Experiences with simultaneous use of contraception and the vaginal ring for HIV prevention in sub-Saharan Africa

• Patterns of Adherence to a Dapivirine Vaginal Ring for HIV-1 Prevention Among South African Women in a Phase III Randomized Controlled Trial

• Acceptability of the Dapivirine Vaginal Ring for HIV-1 Prevention and Association with Adherence in a Phase III Trial

• Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

• Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE

• Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study

• Sharing Objective Measures of Adherence to a Vaginal Microbicide Promotes Candor About Actual Use and Bolsters Motivation to Prevent HIV

• Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women

• Assessment of risk compensation following use of the dapivirine vaginal ring in southwestern Uganda

• Outline Images Download Cite Share Favorites Permissions PREVENTION RESEARCH Brief Report: Phase IIa Safety Study of a Vaginal Ring Containing Dapivirine in Adolescent Young Women