Scale-up and manufacturing prospects
Scale-up prospects
General manufacturing requirements and production scale-up for therapeutic monoclonal antibody (mAb) products is primarily focused on pharmacokinetic suitability, formulation stability and the overall maintenance of product quality. Industrial bioprocessing steps can also potentially introduce additional challenges regarding mAb formulation viscosity and aggregation propensity.
Tentative equipment list for manufacturing
Industrial bioreactor vessel with a production volume capacity of between 5-25kL. Continuous disc stack centrifuges for bioreactor harvesting with subsequent membrane and depth filtration for supernatant clarification. Recombinant protein-A chromatography or other suitable affinity capture apparatus followed by two chromatographic polishing steps such as cation- and anion-exchange. Ultrafiltration membrane system to concentrate and formulate the final product.
Manufacturing
MAbs are highly dependent on their structural, chemical and conformational stability for biological activity. Chemical degradation of mAbs during manufacture can lead to the generation of product variants and complex impurity profiles resulting from a wide range of processes, including: N-linked glycosylation, isomerisation, fragmentation, deamidation, oxidation and C-terminal lysine clipping. Additionally prior to packaging, the final product requires close monitoring for the presence of residual contaminants such as endotoxins and pro-inflammatory peptidoglycans.
Specific analytical instrument required for characterization of
formulation
Formulation characterisation steps for therapeutic mAb products include (but are not limited to): (1) Identification of post-translational modifications using ion-exchange chromatography and capillary isoelectric focusing, (2) Measurement of concentration dependent aggregation rates via thermal differential scanning calorimetry, sub-visible particle quantitation and size-exclusion chromatography, and (3) Antibody clipping and fragmentation detection by capillary electrophoresis.
Clinical trials
TNM001-302
Identifier
NCT06710925
Link
https://clinicaltrials.gov/study/NCT06710925
Phase
Phase III
Status
Not yet recruiting
Sponsor
Zhuhai Trinomab Pharmaceutical Co., Ltd.
More details
This study is a Phase 3 randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, and immunogenicity of TNM001 in high-risk infants when entering their RSV season. Approximately 201 infants will be randomized in a ratio of 2:1 to receive TNM001 or placebo. All subjects will be followed for 270 days after dosing. This study will be conducted at approximately 20 sites in China.
Purpose
A Sudy to Evaluate the Efficacy and Safety of TNM001 in High-risk Infants
Interventions
Intervention 1
TNM001
Intervention 2
placebo
Countries
China
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
2024-11-30
Actual Start Date
Not provided
Anticipated Date of Last Follow-up
2024-11-29
Estimated Primary Completion Date
2027-11-30
Estimated Completion Date
2027-11-30
Actual Primary Completion Date
Not provided
Actual Completion Date
Not provided
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
No
Accepts lactating individuals
No
Accepts healthy individuals
Yes
Comments about the studied
populations
Inclusion Criteria:
* 1.High risk infants under 1 year of age who are entering their first RSV season at the time of screening.
* 2.Subject's legal representative(s) is(are) able to understand and comply with the requirements and procedures of the protocol,including scheduled visits and sample collection.
* 3.Subject is available to complete the follow-up period.
Exclusion Criteria:
* 1. Any fever (\> 38.0°C) or acute illness within 7 days prior to randomization
* 2. History of RSV infection
* 3. Being hospitalized at the time of randomization
* 4. Currently receiving or expected to receive immunosuppressive therapy during the study period.
* 5. Renal impairment or hepatic dysfunction
* 6. Nervous system disease or neuromuscular disease
* 7. Known immunodeficiency including HIV, mother
Health status
Negative to
: HIV
Study type
Interventional (clinical trial)
Enrollment
201
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
Other/Variable/Unknown
:
"Single dose
"
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intramuscular
Use case
Prevention
Key resources
Not provided
TNM001-301
Identifier
NCT06083623
Link
https://clinicaltrials.gov/study/NCT06083623
Phase
Phase II/III
Status
Not yet recruiting
Sponsor
Zhuhai Trinomab Pharmaceutical Co., Ltd.
More details
The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), neutralizing antibody and antidrug antibody (ADA) response for TNM001 in infants entering their first RSV season.
Purpose
A Trial to Evaluate the Efficacy and Safety of TNM001 for the Prevention of Lower Respiratory Tract Infection Caused by Respiratory Syncytial Virus in Infants
Interventions
Intervention 1
TNM001
Intervention 2
placebo
Countries
China
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
2023-10-06
Actual Start Date
Not provided
Anticipated Date of Last Follow-up
2023-10-11
Estimated Primary Completion Date
2026-05-31
Estimated Completion Date
2026-08-31
Actual Primary Completion Date
Not provided
Actual Completion Date
Not provided
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
No
Accepts lactating individuals
No
Accepts healthy individuals
Yes
Comments about the studied
populations
Inclusion Criteria:
* 1. Early and mid-term preterm infants (\<35 weeks 0 day GA) and late preterm infants or full-term infants (≥35 weeks 0 day GA) under 1 year of age, with or without Congenital Heart Disease (CHD) or premature infants Chronic Lung Disease (CLD)，who are entering their first RSV season at the time of screening.
Exclusion Criteria:
* 1. Any fever (\> 38.0°C) or acute illness within 7 days prior to randomization
* 2. History of RSV infection or active RSV infection prior to, or at the time of, randomization
* 3. Drug medication prior to randomization or expected to be treated by medicines during the study period.
* 4. Currently receiving or expected to receive immunosuppressive therapy during the study period.
* 5. Renal impairment or hepatic dysfunction
* 6. Nervous sys
Health status
Negative to
: HIV
Study type
Interventional (clinical trial)
Enrollment
2250
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
Other/Variable/Unknown
:
"Single dose
"
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intramuscular
Use case
Prevention
Key resources
Not provided
TNM001-201
Identifier
NCT05630573
Link
https://clinicaltrials.gov/study/NCT05630573
Phase
Phase I/II
Status
Completed
Sponsor
Zhuhai Trinomab Pharmaceutical Co., Ltd.
More details
The purpose of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics (PK) profile of TNM001 injection in healthy preterm and term infants. The main questions it aims to answer are:
* the safety and tolerability of TNM001 injection
* the pharmacokinetic (PK) profile of TNM001
Purpose
A Study of TNM001 in Chinese Healthy Preterm and Term Infants
Interventions
Intervention 1
Biological: TNM001
Intervention 2
Biological: Placebo
Countries
China
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2022-10-25
Anticipated Date of Last Follow-up
2024-06-26
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2023-06-30
Actual Completion Date
2023-06-30
Studied populations
Age Cohort
Genders
Accepts pregnant individuals
No
Accepts lactating individuals
No
Accepts healthy individuals
Yes
Comments about the studied
populations
Key Inclusion Criteria:
1. Healthy preterm infants and term infants within 1 year old of age.
2. Infants who are in the first RSV infection season at the time of randomization.
Key Exclusion Criteria:
1. Any fever or acute illness within 7 days prior to dosing.
2. LRTI prior to randomization.
3. Received any anti-RSV monoclonal antibody or RSV vaccine.
4. Any other circumstances that, in the opinion of the investigator, may interfere with the assessment of the study drug or the interpretation of the study results.
5. The subject is a child of the investigator or his/her subordinate study personnel or relatives or sponsor staff.
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
31
Allocation
Randomized
Intervention model
Sequential assignment
Intervention
model description
Not provided
Masking
Quadruple-blind masking
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Frequency of administration
Other/Variable/Unknown
:
"Single dose
"
Studied LA-formulation(s)
Injectable
Studied route(s) of administration
Intramuscular
Use case
Prevention
Key resources
Not provided
Supporting material
Publications
Li Y, Tian D, Pan L, et al. Efficacy and Safety of Retavibart, a Long-acting Monoclonal Antibody, for the Prevention of Respiratory Syncytial Virus-Induced Lower Respiratory Tract Infection: A Phase 2b Trial in Infants Entering Their First Epidemic Season. Open Forum Infect Dis. 2026;13(Suppl 1):ofaf695.169. Published 2026 Jan 11. doi:10.1093/ofid/ofaf695.169
Background
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children. Retavibart (formerly known as TNM001) is a recombinant human monoclonal antibody (mAb) targeting the prefusion protein of RSV.
Methods
This was a randomized, double-blind, placebo-controlled phase 2b trial. Eligible participants included term and preterm infants, with or without congenital heart disease (CHD) or chronic lung disease (CLD) of prematurity, who were entering their first RSV season. Participants were randomized in a 2:1 ratio to receive a single intramuscular injection of retavibart 120 mg or placebo. Efficacy endpoints included incidence of medically attended lower respiratory tract infection (MALRTI) and hospitalization due to RT-PCR confirmed RSV infection through Day 151. Safety assessments included the collection of adverse events (AEs) and serious adverse events (SAEs) and monitoring of vital signs within 240 days post-dose.
Results
A total of 760 participants were randomized and 751 received treatment: 500 received retavibart and 251 received placebo. The median age of participants was 2.50 months (range: 0-8.1 months) with a slight male predominance. Ninety-two participants were classified as high-risk, including 65 healthy preterm infants (gestation age < 35 weeks) and 28 with CHD. No infants with CLD were enrolled.
Retavibart reduced the incidence of MALRTI by 66.2% (95% CI: 41.5, 80.5) and RSV-related hospitalization by 82.3% (95% CI: 57.6, 92.6) compared to placebo. Greater efficacy was observed in the high-risk population. In this subgroup, the reduction in RSV-related MALRTIs and hospitalization reached 91.1% and 93.5%, respectively.
The incidences of any AEs and SAEs were comparable between the two groups. No participants died or were early withdrawn from the trial due to AE.
Conclusion
A single dose injection of retavibart 120 mg was well tolerated and had a safety profile comparable to that of placebo. Retavibart showed effective protection against RSV infection in infants during their first season. This was the first clinical trial that compared a long-acting anti-RSV mAb with placebo in the high-risk population. Results showed that retavibart had greater efficacy in this population.
Additional documents
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