Antiretrovirals Combined With Antibodies for HIV-1 Cure In Africa

NCT06205602 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ACTG A5417UM1AI068636
• Study Type: interventional
• Target: 135
• Locations: 2 countries
• Sites: 4

Brief Summary

For people living with HIV, antiretroviral therapy (ART) helps to stop the virus from multiplying. The goal of current HIV treatment is to have such a small amount of the virus in the blood that it does not show up on regular tests. HIV is also hidden in cells throughout the body and can start multiplying when ART is stopped. This research study will test two new study drugs: 10-1074-LS and 3BNC117-LS. Both of these study drugs are antibodies against HIV. An antibody is generally a substance that the body makes in response to an infection. The antibodies being used in this study were made in a laboratory and were designed to attach to HIV and can block HIV from attacking cells in the body and from spreading to other parts of the body. These antibodies are being developed to potentially treat and prevent HIV. The main purpose of this study is to see if the study drugs affect the level of HIV that remains in the blood cells while taking ART and the level of HIV in the blood after discontinuing taking ART. The study will also see if it is safe to give people these antibodies and if they cause any side effects.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (2)

• Occurrence of Grade ≥2 Adverse Events (AE) or Serious Adverse Events (SAE)

  Occurrence of Grade ≥2 AE or SAE that are possibly, probably, or definitely related to the study bNAbs during Step 1 (as judged by the CMC, blinded to active/placebo treatment).

  Day 0 through Week 56

• Time from antiretroviral therapy (ART) discontinuation to sustained HIV-1 RNA ≥ 1000 copies/mL over a 4-week period (through step 2)

  Sustained HIV-1 RNA ≥1000 copies/mL over a 4-week period means at least two measurements of HIV-1 RNA ≥1000 copies/mL over 4 weeks with no HIV-1 RNA \<1000 copies/mL measured between them. Through Step 2 means the 4-week period has started between Step 2 week 0 and week 24.Time to sustained HIV-1 RNA ≥1000 copies/mL over 4 weeks is the time to the first measurement that reaches that level over 4 weeks.

  4 weeks from Step 2 Day 0 (Study week 60, 72 or 84 depending on early pharmacokinetic modeling)

Secondary Outcomes (2)

• Time from ART discontinuation to ART restart

  Time from ART discontinuation (can occur at 60, 72 or 84 weeks) to restart of ART (0 to 72 weeks after ART discontinuation)

• The proportion of participants who undergo ATI without indication of ART restart

  Time from ART interruption(study week 60, 72 or 84) through 24 weeks.

Study Arms (2)

Broadly neutralizing antibodies (bNAbs) infusions with antiretroviral therapy (ART)

ACTIVE COMPARATOR

Drug: 3BNC117-LS; Drug: 10-1074-LS

Placebo infusions with ART

PLACEBO COMPARATOR

Drug: Placebo for 3BNC117-LS; Drug: Placebo for 10-1074-LS

Interventions

3BNC117-LS DRUG

30 mg/kg to be administered via IV at Step 1 (Day 1)

Broadly neutralizing antibodies (bNAbs) infusions with antiretroviral therapy (ART)

10-1074-LS DRUG

10 mg/kg to be administered intravenously at Step 1 (Day 1)

Broadly neutralizing antibodies (bNAbs) infusions with antiretroviral therapy (ART)

Placebo for 3BNC117-LS DRUG

0.9% Sodium Chloride Injection to be administered intravenously at Step 1 (Day 1)

Placebo infusions with ART

Placebo for 10-1074-LS DRUG

0.9% Sodium Chloride Injection) to be administered IV at Step 1 (Day 1)

Placebo infusions with ART

Eligibility Criteria

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

You may qualify if:

• Confirmed HIV-1, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study Step 1 entry AND Confirmed by one of the following:
• A second antibody test from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used)
• HIV-1 antigen
• Plasma HIV-1 RNA viral load or
• A licensed Western blot
• NOTE: The term "licensed" refers to a US FDA or DAIDS Clinical Laboratory Oversight (DCLOT) approved test.
• WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
• ART-naïve \[NOTE: Prior use of PrEP or PEP is allowed, except use of long-acting ARVs (e.g., cabotegravir, rilpivirine) within the last 24 months.\]
• CD4+ T cell count \>200 cells/mm3 obtained within 28 days prior to study entry at any Network-approved non-US laboratory that is (IQA) certified.
• Plasma HIV-1 RNA \>1000 copies/mL obtained within 28 days prior to study entry performed at any Network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance (EQA) programs.
• For study candidates of child-bearing potential, negative urine or serum pregnancy test within 72 hours prior to study entry by any Network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate EQA programs.
• \[NOTE A: Persons who are of child-bearing potential are individuals who have not been post-menopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, and who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy, tubal ligation, or bilateral salpingectomy.\] \[NOTE B: Acceptable documentation of hysterectomy and bilateral oophorectomy, tubal ligation, and tubal micro-inserts are written documentation or oral communication from a clinician or clinician's staff documented in source documents (physician report/letter, operative report or other source documentation in the patient record, discharge summary, laboratory report, etc.). Participant-reported history is acceptable for documentation of menopause.\]
• Persons of child-bearing potential who are able to become pregnant must agree to use two methods of contraception, if participating in sexual activity that could lead to pregnancy. One contraceptive method must be from the list of highly effective methods listed below. The second method of contraception must be a barrier method or abstinence. Both methods of contraception must be used during Step 1. The two effective forms of birth control have to be used for 10 days before receiving the first study drug infusion, for at least 12 months after the product infusion, and until ART is reinitiated and viral suppression is achieved.
• Acceptable methods of contraception include:
• Contraceptive subdermal implant

You may not qualify if:

• Any clinically significant acute or chronic medical condition, other than HIV, that in the opinion of the investigator would preclude safe participation in the study or interfere with the validity of study results.
• History of AIDS-defining illness within 3 years prior to enrollment.
• History of systemic corticosteroids (e.g., an equivalent dose of prednisone of \> 20 mg daily for \>14 days), immunosuppressive anti-cancer, interleukins, systemic interferons, systemic chemotherapy or other medications considered significant by the trial physician within the last 12 weeks.
• History of a severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis in the 2 years prior to enrollment.
• History of chronic urticaria requiring current daily treatment.
• Known history of active Hepatitis B or Hepatitis C infection. \[NOTE: Participant is eligible if hepatitis C virus (HCV) cure or clearance is documented.\]
• History of or current clinical atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including a previous diagnosis of any of the following:
• Acute myocardial infarction
• Acute coronary syndromes
• Stable or unstable angina
• Coronary or other arterial revascularization
• Stroke
• Transient ischemic attack
• Peripheral arterial disease presumed to be of atherosclerotic origin
• Any history of receipt of HIV vaccine candidate or HIV-specific monoclonal antibody therapy.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (4)

Gaborone CRS (12701)

Gaborone, Botswana

RECRUITING

University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101)

Johannesburg, Gauteng, 2193, South Africa

RECRUITING

CAPRISA eThekwini CRS (31422)

Durban, KwaZulu-Natal, 4011, South Africa

RECRUITING

Durban Adult HIV CRS (11201)

Durban, 4013 SF, South Africa

RECRUITING

Study Officials

• Trevor Crowell, MD, PhD

  US Military HIV Research Program CTU

  STUDY CHAIR

• Wadzanai Samaneka, MBChB, MSc

  Milton Park CRS

  STUDY CHAIR

Central Study Contacts

ACTG CT.gov Coordinator

CONTACT

(301)628-3348; ACTGCT.gov@dlhcorp.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 16, 2024
• Study Start: January 17, 2025
• Primary Completion (Estimated): February 16, 2029
• Study Completion (Estimated): February 16, 2029
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal-2/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

ZA (3); BO (1)