Dose Escalation Safety Study of TMB-365 in HIV-1 Infected Participants

NCT04027387 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TMB-365-101
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 6

Brief Summary

This study will evaluate the safety and behavior in the body of the experimental drug TMB-365 in people with HIV-1 infection. This will be the first test of TMB-365 in humans. One dose of the study drug is given to each participant, followed by 10 weeks of monitoring for safety and levels of the drug in the blood. The first group of participants will receive the lowest dose (400 mg). If no safety concerns are seen, the next group will begin at a higher dose (800 mg). If no safety concerns are seen in the second group, the third group will begin at the highest dose in this study (1600 mg).

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (6)

• Safety of a single 400mg dose of TMB-365

  % of subjects with treatment-emergent adverse events

  10 weeks

• Safety of a single 800mg dose of TMB-365

  % of subjects with treatment-emergent adverse events

  10 weeks

• Safety of a single 1600mg dose of TMB-365

  % of subjects with treatment-emergent adverse events

  10 weeks

• Pharmacokinetics of a single 400mg dose of TMB-365

  % CD4 receptor occupancy

  4 weeks

• Pharmacokinetics of a single 800mg dose of TMB-365

  % CD4 receptor occupancy

  4 weeks

• Pharmacokinetics of a single 1600mg dose of TMB-365

  % CD4 receptor occupancy

  4 weeks

Secondary Outcomes (3)

• Antiviral activity of a single 400 mg dose of TMB-365

  2 weeks

• Antiviral activity of a single 800 mg dose of TMB-365

  2 weeks

• Antiviral activity of a single 1600 mg dose of TMB-365

  2 weeks

Study Arms (3)

TMB-365 400 mg- Group 1

EXPERIMENTAL

Single dose of TMB-365 400 mg or matching placebo by intravenous infusion

Biological: TMB-365

TMB-365 800 mg- Group 2

EXPERIMENTAL

Single dose of TMB-365 800 mg or matching placebo by intravenous infusion

Biological: TMB-365

TMB-365 1600 mg- Group 3

EXPERIMENTAL

Single dose of TMB-365 1600 mg or matching placebo by intravenous infusion

Biological: TMB-365

Interventions

TMB-365 BIOLOGICAL

An IgG1 monoclonal antibody targeting domain 2 of the CD4 receptor for treatment of HIV-1 infection

TMB-365 1600 mg- Group 3; TMB-365 400 mg- Group 1; TMB-365 800 mg- Group 2

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
• Has not received ART for three months prior to the first dose.
• Screening HIV-1 RNA ≥ 1,000 copies/mL and \< 100,000 copies/mL obtained within 60 days prior to the first dose.
• Laboratory values obtained within 60 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)
• 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:

• Receipt of TMB-365, TROGARZO (ibalizumab-uiyk), or any anti-CD4 therapeutic (e.g., UB-421) at any time prior to the first dose
• 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, bipolar disorder requiring 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 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. Note that a change in treatment regimen for intolerance is not considered treatment failure.

Sponsors & Collaborators

• TaiMed Biologics Inc.: lead
• Westat: collaborator

Study Sites (6)

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

University of Mississippi Medical Center Division of Infectious Diseases

Jackson, Mississippi, 39213, United States

Location

North Texas Infectious Disease Consultants

Dallas, Texas, 75246, United States

Location

Clinical Research PR, Inc

San Juan, 00909, Puerto Rico

Location

Study Officials

• Steve Weinheimer, PhD

  TaiMed Biologics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind placebo controlled. Study pharmacist unblinded.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single dose escalation

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 22, 2019
• Study Start: December 14, 2019
• Primary Completion: August 18, 2021
• Study Completion: August 18, 2021
• Last Updated: October 6, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (5)