10E8.4/iMab

Drug information

Delivery device(s)

Not provided

Scale-up prospects

Not provided

Tentative equipment list for manufacturing

Not provided

Manufacturing

Not provided

Specific analytical instrument required for characterization of formulation

Not provided

AAAS1239

Identifier

NCT03875209

Link

https://clinicaltrials.gov/study/NCT03875209

Phase

Phase I

Status

Completed

Sponsor

David Ho

More details

Many HIV-infected individuals mount a broad neutralizing serologic response 2-3 years after infection. Broadly neutralizing antibodies might play an important role in protection from acquisition of HIV infection because they can protect macaques from infection, and the presence of anti-HIV antibodies was the only positive correlate of protection in an HIV vaccine efficacy trial (RV144 trial). HIV neutralizing antibodies also have the potential to alter the course of HIV infection in humans. Therefore, these antibodies might be useful to both prevent and treat HIV-1 infection. This is a phase 1 dose escalating clinical trial to evaluate the safety, tolerability, pharmacokinetics and the antiretroviral effects of a novel bispecific monoclonal antibody 10E8.4/iMab in HIV-infected and HIV-uni

Purpose

10E8.4/iMab Bispecific Antibody in HIV-uninfected and HIV-infected Adults

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-04-08

Anticipated Date of Last Follow-up
2023-03-06

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2022-03-23

Actual Completion Date
2022-03-23

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria for HIV uninfected volunteers: Arms 1, 2 and 4: * Healthy volunteers born male and female as assessed by medical history and physical examination * Aged \>18 and \<60 years at the time of screening * Ability and willingness to provide written informed consent * Willingness to comply with protocol schedule * Willingness to undergo HIV-1 testing * Non-reactive 4th generation point of care HIV-1 test at screening * Hepatitis B Surface antigen negative * Hepatitis C antibody negative, or if reactive, Hepatitis C RNA undetectable in plasma * Volunteers born female of reproductive potential, sexually active with a male sex partner must agree to use one effective method of contraception from the time of signing the consent to completion of the study and agree to pregnancy test

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

54

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

Unspecified

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

Bispecific 10E8.4/iMab broadly neutralizing antibody in people with or without HIV-1: a partially randomized phase 1 trial

Theodore, D.A. — Nature Medicine — 2026-07-07

Broadly neutralizing antibodies (bnAbs) are a promising tool for HIV prevention and treatment. Here we conducted a first-in-human, phase 1 trial of the bispecific 10E8.4/iMab antibody, which consists of a 10E8.4 arm binding the HIV-1 envelope glycoprotein membrane-proximal external region and an ibalizumab (iMab) arm binding the human CD4 molecule. 10E8.4/iMab was administered intravenously (IV) or subcutaneously (SC). Safety/tolerability within 2 weeks of 10E8.4/iMab administration (primary outcome) and the pharmacokinetics (PK), antiviral activity, induction of anti-10E8.4/iMab antibodies, longitudinal CD4+ and CD8+ T cell counts and long-term safety (secondary outcomes) were evaluated. 54 participants living with HIV (PLWH) or without HIV (PLWoH) received 10E8.4/iMab or placebo. In arm 1, PLWoH received 10E8.4/iMab 0.3 mg kg−1 IV, 1 mg kg−1 SC, or 1 mg kg−1 IV (n = 3 each). In arm 2, PLWoH received 10E8.4/iMab 3 mg kg−1 IV, 10 mg kg−1 IV or 30 mg kg−1 IV (n = 6 each). In arms 3/3a, PLWH received 10E8.4/iMab 10 mg kg−1 IV (n = 3) or 30 mg kg−1 IV (n = 6). In arm 4, PLWoH were randomized to receive 10E8.4/iMab or placebo 2.5 mg kg−1 SC or 10 mg kg−1 SC (n = 9 each). Participants in arms 1–3 were not randomized. No treatment-related serious adverse events (AEs) or AEs ≥ grade 3 were reported. The most common solicited AEs were tenderness (10/54, 18.5%), fatigue (18/54, 33.3%) and headache (12/54, 22.2%). Related grade 2 local and systemic solicited AEs occurred in one and six participants, respectively. Three of nine PLWH developed a generalized rash 8–12 days after infusion that resolved within 9–16 days. The primary objective of the study to evaluate the safety/tolerability of 10E8.4/iMab was met. These data support further study of 10E8.4/iMab to expand HIV treatment and prevention options

Additional documents

No documents were uploaded

Useful links

• Bispecific 10E8.4/iMab broadly neutralizing antibody in people with or without HIV-1: a partially randomized phase 1 trial — Nature Medicines, 2026-07-07

• 10e8.4/iMAb Bispecific Antibody for Immunoprophylaxis Against High-Dose Intravenous SHIV Exposure — CROI 2024, 2024-02-14