TMB-365 and TMB-380 in Suppressed HIV-1 Infected Individuals

NCT05275998 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: TMB-a21
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

HIV-1-infection

Keywords

HIV-1 treatment, monoclonal antibodies

Outcome Measures

Primary Outcomes (6)

• Safety of TMB-365 and TMB-380 Given Intravenously (Sentinel and Core)

  Grade 3, Grade 4, Serious Adverse reactions related to TMB-365 and TMB-380 infusions

  12 weeks (Sentinel Group 1), 16 weeks (Sentinel Group 2, 3), 28 weeks (Core Group)

• Pharmacokinetics of a Single Dose TMB-365 Given Intravenously (Sentinel)

  In the Sentinel Group, participants received a single dose of TMB-365 and TMB-380 at 2400 mg, 3200 mg, or 4800 mg each. TMB-365 concentrations were measured using a validated ELISA, and the Week 8 concentration was used to guide dose selection for the Core Group.

  Week 8

• Pharmacokinetics of TMB-365 Given Intravenously Every 8 Weeks (Core)

  Core Group participants received 4800 mg every 8 weeks.TMB-365 concentrations were measured using a validated ELISA. Trough concentrations are reported.

  Week 8, 16, and 24

• Pharmacokinetics of a Single Dose TMB-380 Given Intravenously (Sentinel)

  In the Sentinel Group, participants received a single dose of TMB-365 and TMB-380 at 2400 mg, 3200 mg, or 4800 mg each. TMB-380 concentrations were measured using a validated ELISA, and the Week 8 concentration was used to guide dose selection for the Core Group.

  Week 8

• Pharmacokinetics of TMB-380 Given Intravenously Every 8 Weeks (Core)

  Core Group participants received 4800 mg every 8 weeks.TMB-380 concentrations were measured using a validated ELISA. Trough concentrations are reported.

  Weeks 8, 16, and 24

• Antiviral Activity of the Combination of TMB-365 in Combination With TMB-380 as Maintenance Therapy (Core)

  Plasma HIV-1 level below 50 copies/mL in study subjects at week 24 during maintenance therapy with TMB-365/TMB-380 infusions in Core Subjects only.

  Week 24

Secondary Outcomes (1)

• Resistance to TMB-365 and TMB-380 (Core)

  24 weeks

Study Arms (4)

Sentinel Group 1

EXPERIMENTAL

10 HIV-1 infected subjects will receive one infusion of 2400 mg of each antibody, TMB-365 and TMB-380 and be followed for safety and pharmacokinetics. Oral suppressive cART will be continued throughout the course of the study participation.

Drug: TMB-365/TMB-380

Sentinel Group 2

EXPERIMENTAL

10 HIV-1 infected subjects will receive one infusion of 3200 mg of each antibody, TMB-365 and TMB-380 and be followed for safety and pharmacokinetics. Oral suppressive cART will be continued throughout the course of the study participation.

Drug: TMB-365/TMB-380

Sentinel Group 3

EXPERIMENTAL

10 HIV-1 infected subjects will receive one infusion of 4800 mg of each antibody, TMB-365 and TMB-380 and be followed for safety and pharmacokinetics. Oral suppressive cART will be continued throughout the course of the study participation.

Drug: TMB-365/TMB-380

Core Group 1

EXPERIMENTAL

20 HIV-1 infected subjects will receive 4800 mg infusions of each antibody, TMB-365 and TMB-380 every 8 weeks and be followed for safety, pharmacokinetics, and ability to maintain antiviral activity. Oral suppressive cART will be discontinued for 24 weeks then resumed at week 24 with follow-up at week 28.

Drug: TMB-365/TMB-380

Interventions

TMB-365/TMB-380 DRUG

Monoclonal antibodies to be given intravenously

Also known as: TMB-380 is also known as VRC07-523-LS

Core Group 1; Sentinel Group 1; Sentinel Group 2; Sentinel Group 3

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female at least 18 years of age and no greater than 60 years on the day of Screening.
• 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.
• 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.
• Screening plasma HIV-1 RNA below the limit of detection.
• CD4+ T cell count \>350 cells/mm3
• 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.
• Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
• 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.
• 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.

You may not qualify if:

• Participants having or meeting any of the following conditions or characteristics will be excluded from the study:
• Suppressed subjects who have not been on a stable DHHS recommended cART regimen for at least 3 months.
• Receipt of any monoclonal antibody for the treatment or prevention of HIV infection except for Sentinel subjects eligible for enrollment into Core groups.
• Suppressed subjects receiving cabotegravir and rilpivirine intramuscularly as maintenance therapy for HIV-1 infection.
• Pregnant, planning a pregnancy during the trial period, or lactating.
• Known allergy/sensitivity or any hypersensitivity to components of the study drug or its formulation, or known allergy to a MAb.
• 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.
• Serious illness requiring systemic treatment and/or hospitalization within 21 days prior to the first dose.
• 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.
• 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.
• Lack of adequate venous access.
• 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.

Sponsors & Collaborators

• TaiMed Biologics Inc.: lead

Study Sites (6)

Quest Clinical Research

San Francisco, California, 94115, United States

Location

CAN Community Health

Fort Lauderdale, Florida, 33316, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34892, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

North Texas Infectious Disease Consultants

Dallas, Texas, 75246, United States

Location

Crofoot Research Center, Inc.

Houston, Texas, 77098, United States

Location

Results Point of Contact

• Title: Dr. Kuei-Ling Kuo
• Organization: TaiMed Biologics

kkuo@taimedbio.com

+886-2-26580058

Study Officials

• Jay Lalezari, MD

  Quest Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2022
• First Posted: March 11, 2022
• Study Start: July 5, 2022
• Primary Completion: November 20, 2024
• Study Completion: November 20, 2024
• Last Updated: October 22, 2025
• Results First Posted: October 22, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)