A Phase 1b/2 Dose Escalation Study of the Safety, Pharmacokinetics, and Efficacy of the Combination of TMB-365 and TMB-380 in HIV-1 Infected Individuals Suppressed With Combination Antiretroviral Therapy

TMB-a21

TMB-365 is a monoclonal antibody that binds to the CD4 receptor. TMB-380, aka VRC-07-523LS is a monoclonal antibody that binds to HIV. Both interfere with HIV entry. This study is designed to test various doses of the combination of the antibodies for safety and pharmacokinetics in suppressed subjects on cART. Once dosing is established based on safety and PK, the optimally dosed combinations will be assessed as maintenance therapy in HIV infected suppressed individuals discontinuing oral cART for 24 weeks.

2022-07-05

2024-04-30

2024-07-30

Recruiting

Early phase I

90

Inclusion Criteria:Participants must meet all of the following criteria to be included in the study: 1. Male or female at least 18 years of age and no greater than 60 years on the day of Screening. 2. Asymptomatic HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by Geenius™ or a second antibody test by a method other than the initial rapid HIV and/or E/CIA test, or by HIV-1 antigen, plasma HIV-1 RNA viral load at or piror to screening. 3. On continuous suppressive cART for 6 months prior to screening with one documented HIV-1 RNA level below the level of detection within 3 months of screening. Continuous cART is defined as no interruptions greater than 3 consecutive days. cART is defined as a DHHS recommended regimen. Study participants should be on a stable regimen, at least 3 months. 4. Screening plasma HIV-1 RNA below the limit of detection. 5. CD4+ T cell count \>350 cells/mm3 6. Laboratory values obtained within 30 days prior to the first dose: * Hemoglobin \> 10.0 g/dL; * Platelet count ≥ 100,000/mm3; * Absolute neutrophil count ≥ 1,000/mm3; * Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 1.5 x upper limit of normal (ULN); and * Creatinine clearance (CrCl) of ≥ 50 mL/min. 7. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study. 8. In the opinion of the principal investigator or designee, has understood the information provided; written informed consent needs to be given before any study-related procedures are performed. 9. Females of childbearing 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 testing as per the Schedule of Events and Procedures. Females of childbearing potential are female participants who are not surgically sterile (no history of bilateral tubal ligation, hysterectomy, or bilateral salpingo-oophorectomy), are not postmenopausal (at least one year without menses), and are not otherwise sterile by medical evaluation. - Exclusion Criteria: Participants having or meeting any of the following conditions or characteristics will be excluded from the study: 1. Suppressed subjects who have not been on a stable DHHS recommended cART regimen for at least 3 months. 2. Receipt of any monoclonal antibody for the treatment or prevention of HIV infection except for Sentinel subjects eligible for enrollment into Core groups. 3. Suppressed subjects receiving cabotegravir and rilpivirine intramuscularly as maintenance therapy for HIV-1 infection. 4. Pregnant, planning a pregnancy during the trial period, or lactating. 5. Known allergy/sensitivity or any hypersensitivity to components of the study drug or its formulation, or known allergy to a MAb. 6. Major psychiatric illness including any history of schizophrenia or severe psychosis, uncontrolled bipolar disorder requiring acute therapy, or suicide attempt in the previous three years. 7. Serious illness requiring systemic treatment and/or hospitalization within 21 days prior to the first dose. 8. Receipt of immunomodulatory agents (e.g., interleukins, interferons, cyclosporine, high dose systemic corticosteroids), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 180 days prior to the first dose. 9. Any chronic or acute medical condition, including chronic Hepatits B infection, chronic Hepatitis C infection with viremia, and drug use and alcohol abuse, which in the opinion of the investigator would interfere with evaluation of the study drug. 10. Lack of adequate venous access. 11. Individuals who have experienced virologic failure during treatment with two or more cART treatment regimens and those being treated with regimens containing either ibalizumab, enfuvirtide, maraviroc, and fostemsavir. Note that a change in treatment regimen for intolerance does not meet criteria for virologic failure. -

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2024-03-13