Semzuvolimab (UB-421)

Drug information

Delivery device(s)

No delivery device

Scale-up prospects

Not reported for this product. Generic monoclonal antibody scale-up considerations apply: formulation stability, maintenance of critical quality attributes, and the higher concentrations needed for a subcutaneous presentation.

Tentative equipment list for manufacturing

Not reported for this product. Standard therapeutic mAb train assumed: production bioreactors, continuous disc-stack centrifugation and depth/membrane filtration for harvest clarification, Protein A and polishing chromatography, viral inactivation and filtration, ultrafiltration/diafiltration, sterile fill-finish.

Manufacturing

Recombinant humanised IgG1 produced in mammalian cell culture; aglycosylated Fc. Detailed cell line, process and facility information has not been published.

Specific analytical instrument required for characterization of formulation

Not reported for this product. Standard mAb characterisation applies: ion-exchange chromatography and capillary isoelectric focusing for charge variants, size-exclusion chromatography for aggregates, DSC for thermal stability, subvisible particle counting, and binding/potency assays (CD4 receptor occupancy by flow cytometry).

UBP-A202-HIV

Identifier

NCT02369146

Link

https://clinicaltrials.gov/study/NCT02369146

Phase

Phase II

Status

Completed

Sponsor

United BioPharma

More details

The purpose of this phase II study is to evaluate the safety, tolerability and efficacy of two multi-dose regimens of UB-421 monotherapy in replacement of HAART in HIV-1 infected adults with virological suppression.

Purpose

To Investigate the Safety and Efficacy of UB-421 Monotherapy in HIV Infected Adults

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-06-01

Anticipated Date of Last Follow-up
2017-10-29

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2016-07-01

Actual Completion Date
2016-07-01

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * HIV-1 sero-positive * Aged 20 years or older * Have received HAART treatment * CD4+ T cell count ≧ 350 cells/mm3 * HIV-1 plasma RNA level remains below the limit of * Were not breastfeeding for women * Subjects with a negative serum pregnancy test result at screening visit for women of childbearing potential * Subjects agree on using birth control barrier (female or male condom) during the entire study period * Subjects sign the informed consent before undergoing any study procedures Exclusion Criteria: * Any active infection except for HIV, and required immediate therapy * Any active AIDS-defining illness per Category B and Category C conditions according to the U.S. Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection * Any doc

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

29

Allocation

Not provided

Intervention model

Parallel 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

Treatment

Key resources

Proprietary excipients used

Not provided

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

Not provided

Residual solvents used

Not provided

There are either no relevant patents or these were not yet submitted to LAPaL

Publications

Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption

Chang-Yi Wang — NEJM — 2019-04-17

Background

Administration of a single broadly neutralizing human immunodeficiency virus (HIV)–specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.

Methods

We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter).

Results

A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy.

Conclusions

UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash.

Additional documents

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Useful links

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