10E8.4/iMab Bispecific Antibody and VRC07-523LS Monoclonal Antibody in HIV-infected Adults

NCT05890963 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: AAAU5207W81XWH-18-2-0040RV584
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label phase 1b clinical trial enrolling people living with HIV (PLWH) who are antiretroviral therapy (ART)-naïve or have not been on ART for \> 24 weeks. This study will enroll PLWH to assess the safety, tolerability, and antiviral effect of bispecific and long-acting bNAbs, alone and in combination. The study will be conducted as a single center study at National Institute for Medical Research-Mbeya Medical Research Center (NIMR-MMRC) in Mbeya, Tanzania. 20 PLWH will be sequentially enrolled into one of 5 arms, each arm comprised of 4 participants. Sequential enrollment will occur in the following order:

• Arm 1 will receive standard daily oral ART.
• Arm 2 will receive a single dose of 10E8.4/iMab 600mg intravenous injection (IV).
• Arm 3 will receive a single dose of 10E8.4/iMab 600mg intramuscular injection (IM).
• Arm 4 will receive a single dose of 10E8.4/iMab 1800mg IV.
• Arm 5 will receive a single dose of combination therapy with both 10E8.4/iMab 1800mg IV and VRC07-523LS 1200mg IV.

Conditions

HIV-1-infection

Keywords

Antiretroviral therapy (ART); VRC07-523LS; 10E8.4/iMab; Monoclonal antibody; Bispecific antibody; Broadly neutralizing antibodies; Viral suppression; Ibalizumab; 10E8

Outcome Measures

Primary Outcomes (3)

• Number of Grade 3 or higher antibody-related reactogenicity and adverse events

  Includes potentially life-threatening, or fatal events.

  Up to Week 48 in Step 2

• Change in plasma HIV RNA from day 0 to day 14

  Viral RNA copies/mL will be measured.

  Day 0 and Day 14 in Step 1

• Proportion of participants with HIV RNA < 50 copies/mL at day 14

  Percentage of participants will be calculated.

  Up to Day 14 in Step 1

Secondary Outcomes (11)

• Proportions of participants with HIV RNA <50 copies/mL

  Up to Week 48 in Step 2

• Proportions of participants with HIV RNA < 200 copies/mL

  Up to Week 48 in Step 2

• Proportions of participants with HIV RNA <1000 copies/mL

  Up to Week 48 in Step 2

• Peripheral HIV RNA

  Up to Week 48 in Step 2

• Plasma level of 10E8.4/iMab

  Up to Week 48 in Step 2

Study Arms (5)

Arm 1: Oral ART

ACTIVE COMPARATOR

Participants will receive standard daily oral ART.

Drug: ART

Arm 2: 10E8.4/iMab 600mg IV.

EXPERIMENTAL

Participants will receive a single dose of 10E8.4/iMab 600mg IV.

Drug: 10E8.4/iMab

Arm 3: 10E8.4/iMab 600mg IM.

EXPERIMENTAL

Participants will receive a single dose of 10E8.4/iMab 600mg IM.

Drug: 10E8.4/iMab

Arm 4:10E8.4/iMab 1800mg IV.

EXPERIMENTAL

Participants will receive a single dose of 10E8.4/iMab 1800mg IV.

Drug: 10E8.4/iMab

Arm 5: Combination 10E8.4/iMab and VRC07-523LS therapy

EXPERIMENTAL

Participants will receive a single dose of combination therapy with both 10E8.4/iMab 1800mg IV. and VRC07-523LS 1200mg IV.

Drug: 10E8.4/iMab; Drug: VRC07-523LS

Interventions

ART DRUG

ART is a combination of three or more drugs from different classes of antiretroviral medication.

Also known as: antiretroviral therapy

Arm 1: Oral ART

10E8.4/iMab DRUG

10E8.4/iMab is an engineered bispecific antibody with two arms combined into a single molecule that exhibits synergistic enhancement of antiviral activity. 10E8.4/iMab will be administered IV at the 600mg or 1800mg dose or IM at 600mg dose to participants in Step 1 per the Schedule of Events (SOE) based on the arm the participant is assigned.

Also known as: ibalizumab

Arm 2: 10E8.4/iMab 600mg IV.; Arm 3: 10E8.4/iMab 600mg IM.; Arm 4:10E8.4/iMab 1800mg IV.; Arm 5: Combination 10E8.4/iMab and VRC07-523LS therapy

VRC07-523LS DRUG

VRC07-523LS is an engineered variant of VRC01, a bNAb that targets the CD4 binding site of the HIV-1 envelope. VRC07-523LS will be administered IV at the 1200mg dose to participants in Step 1 per the SOE.

Also known as: VRC01 variant

Arm 5: Combination 10E8.4/iMab and VRC07-523LS therapy

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Able to read and write in Kiswahili and/or English
• Able and willing to provide written informed consent
• Passes Test of Understanding (TOU)
• Aged 18-50 years, inclusive
• Antiretroviral Therapy (ART)-naïve or no ART for \> 24 weeks at the time of screening
• HIV RNA 1,000-100,000 copies/mL
• CD4 ≥ 500 cells/mm3
• Laboratory criteria at screening within protocol-specified limits for blood, chemistry and urinalysis
• Willing and able to participate in study visits and procedures for up to 50 weeks
• Willing and able to begin ART as directed during the study
• Willing and able to use barrier protection during sex with partners without HIV or partners with unknown HIV status throughout Step 1 and until viral suppression \<200 copies/mL is confirmed in Step 2
• Willing and able to adhere to the following contraception requirements:
• Participants who are able to become pregnant must agree to use at least one method of highly effective contraception if participating in sexual activity that could lead to pregnancy. This must begin at least 14 days prior to study enrollment.
• Participants who engage in sexual activity that could lead to their partner becoming pregnant and who are of reproductive potential must agree to use a barrier method of contraception to avoid pregnancy in a sexual partner of reproductive potential. The barrier method must be used for the duration of the study.

You may not qualify if:

• Weight \>100 kg
• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational (other than for the prevention and/or treatment of SARS-CoV2/COVID-19)
• History of viral failure on two or more ART regimens
• Planned or anticipated need for enfuvirtide, maraviroc, fostemsavir, or ibalizumab for antiretroviral therapy.
• AIDS-defining illness, as enumerated by the WHO Stage 3 or 4, within the six months prior to enrollment
• Ongoing oral thrush
• Active injection or other recreational drug use within the previous 12 months that, in the opinion of the investigator, would impede the participant's ability to safely and consistently adhere to the study protocol
• History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis in the 2 years prior to enrollment.
• History of chronic urticaria requiring daily treatment
• Known active hepatitis B virus infection or positive hepatitis B surface antigen at any time in the past
• Known active hepatitis C virus infection or positive hepatitis C antibody at any time in the past
• Untreated syphilis
• Estimated GFR \< 50 mL/min within the past 90 days
• Pregnant or breast-feeding
• Receipt of licensed vaccine or other investigational study agent within 28 days prior to enrollment or any past participation in an investigational HIV vaccine study with receipt of active product

Sponsors & Collaborators

• David Ho: lead
• Henry M. Jackson Foundation for the Advancement of Military Medicine: collaborator
• US Military HIV Research Program: collaborator
• National Institute of Allergy and infectious Diseases (NIAID)/Vaccine Research Center (VRC): collaborator

Study Sites (1)

National Institute for Medical Research-Mbeya Medical Resarch Center

Mbeya, Tanzania

Location

Related Publications (9)

• Huang Y, Yu J, Lanzi A, Yao X, Andrews CD, Tsai L, Gajjar MR, Sun M, Seaman MS, Padte NN, Ho DD. Engineered Bispecific Antibodies with Exquisite HIV-1-Neutralizing Activity. Cell. 2016 Jun 16;165(7):1621-1631. doi: 10.1016/j.cell.2016.05.024.

  PMID: 27315479 BACKGROUND

• Mahomed S, Garrett N, Capparelli EV, Osman F, Harkoo I, Yende-Zuma N, Gengiah TN, Archary D, Samsunder N, Baxter C, Mkhize NN, Modise T, Carlton K, McDermott A, Moore PL, Karim QA, Barouch DH, Fast PE, Mascola JR, Ledgerwood JE, Morris L, Abdool Karim SS. Safety and Pharmacokinetics of Monoclonal Antibodies VRC07-523LS and PGT121 Administered Subcutaneously for Human Immunodeficiency Virus Prevention. J Infect Dis. 2022 Aug 26;226(3):510-520. doi: 10.1093/infdis/jiac041.

  PMID: 35134995 BACKGROUND

• Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, Imamichi H, Bailer RT, Chakrabarti B, Sharma SK, Alam SM, Wang T, Yang Y, Zhang B, Migueles SA, Wyatt R, Haynes BF, Kwong PD, Mascola JR, Connors M. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature. 2012 Nov 15;491(7424):406-12. doi: 10.1038/nature11544. Epub 2012 Sep 18.

  PMID: 23151583 BACKGROUND

• Burkly LC, Olson D, Shapiro R, Winkler G, Rosa JJ, Thomas DW, Williams C, Chisholm P. Inhibition of HIV infection by a novel CD4 domain 2-specific monoclonal antibody. Dissecting the basis for its inhibitory effect on HIV-induced cell fusion. J Immunol. 1992 Sep 1;149(5):1779-87.

  PMID: 1380539 BACKGROUND

• Jacobson JM, Kuritzkes DR, Godofsky E, DeJesus E, Larson JA, Weinheimer SP, Lewis ST. Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults. Antimicrob Agents Chemother. 2009 Feb;53(2):450-7. doi: 10.1128/AAC.00942-08. Epub 2008 Nov 17.

  PMID: 19015347 BACKGROUND

• Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997 Nov 14;278(5341):1295-300. doi: 10.1126/science.278.5341.1295.

  PMID: 9360927 BACKGROUND

• Wolfe D, Carrieri MP, Shepard D. Treatment and care for injecting drug users with HIV infection: a review of barriers and ways forward. Lancet. 2010 Jul 31;376(9738):355-66. doi: 10.1016/S0140-6736(10)60832-X.

  PMID: 20650513 BACKGROUND

• Jaworski JP, Cahn P. Preventive and therapeutic features of broadly neutralising monoclonal antibodies against HIV-1. Lancet HIV. 2018 Dec;5(12):e723-e731. doi: 10.1016/S2352-3018(18)30174-7. Epub 2018 Sep 21.

  PMID: 30245003 BACKGROUND

• Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7. doi: 10.1073/pnas.94.24.13193.

  PMID: 9371822 BACKGROUND

MeSH Terms

Interventions

Antiretroviral Therapy, Highly Active; ibalizumab

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Study Officials

• Marco Missanga, MD

  NIMR-MMRC

  PRINCIPAL INVESTIGATOR

• David D. Ho, MD

  Columbia University Irving Medical Center (IND Sponsor)

  PRINCIPAL INVESTIGATOR

• Trevor A. Crowell, MD, PhD

  The U.S. Military HIV Research Program (MHRP)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Participants are assigned to 1 to 5 arm sequentially.

Study Record Dates

• First Submitted: May 26, 2023
• First Posted: June 6, 2023
• Study Start: November 28, 2023
• Primary Completion: April 14, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After completion of the study.
• Access Criteria: Data will only be shared with proper approvals in place to entities that are approved to access the data according to the sponsor.

Locations

TA (1)