Phase II Trial of ART + Dual bNAbs vs. ART + Placebo During Primary HIV-1 Infection-impact on Post-ART Control (RHIVIERA-02)

ANRS, Emerging Infectious Diseases

Status and phase: Enrolling; Phase 2

Conditions: HIV/AIDS and Infections

Treatments: Drug: Placebo; Drug: Recombinant human monoclonal antibody (bNAbs)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05300035

ANRS 176 RHIVIERA-02

Details and patient eligibility

About

RHIVIERA-02 trial is a placebo-controlled double-blinded two arm prospective phase II trial. This study will test the use of broadly neutralising antibodies (bNAbs) in participants, at primary HIV infection (PHI) and ART initiation.

Full description

The study proposes to test an intervention consisting of dual long-acting HIV-specific broadly neutralizing antibodies (3BNC117-LS & 10-1074-LS ) + ART, at primary HIV-1 infection, and to compare it to ART only regarding HIV-1 replication.

The study aims to enrol 69 participants in French (Ile-de-France) clinical centres. Participants will have been diagnosed with primary HIV-1 infection, will start ART during early phase of Primary HIV infection, and will interrupt ART 52 weeks later.

Study duration will vary by participant, depending on the time of ART interruption and the time to viral rebound.

Enrollment: 69 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed primary HIV-1 infection diagnostic
• Aged ≥18 to ≤70 years old at screening
• Willing to use use an effective method of contraception from the inclusion until the end of the follow-up in the trial
• Negative plasmatic beta human chorionic gonadotropin (β-HCG) pregnancy test, when applicable
• Agree not to seek pregnancy including through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit, when applicable
• Informed and written signed consent
• Participant with regular health insurance
• Willing to accept the trial constraints (travel for IMP administration and ART interruption)
• Willing to be vaccinated against COVID-19 according to recommandations

Exclusion criteria

• Participation in any other clinical trial requiring additional blood sampling Participation in an observational study without additional blood sampling is permitted
• Participants in whom condom use or PrEP use by the partner will be difficult or impossible
• Pregnant or breastfeeding patient
• Participants under guardianship or curatorship
• Any condition or infection, including HCV, HBV, SARS-CoV-2 or known M. tuberculosis active infection History of ischemic heart disease (myocardial infarction, stable or unstable angina, stroke)
• Current or past history of cancer, excluding squamous cell skin cancers
• History or acute known inflammatory ophthalmic affection (uveitis, choroiditis, optic neuropathy)
• Any medical condition that contraindicates ART interruption
• Concomitant or previous conditions that preclude injection of monoclonal antibodies
• History of systemic corticosteroids, immunosuppressive and anti-cancer medications within the last 6 months
• History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions
• Individuals with any contraindication (including hypersensitivity reaction) to 3BNC117-LS and 10-1074-LS infusion
• Prothrombin < 50%
• Creatinine clearance < 60mL/mn (Cockroft)
• ASAT or ALAT or bilirubine (total et conjugated) ≥ 10 times the upper limit of normal
• Patient with an isolated HIV-2 viral strain
• Planned absence that could affect participation in the trial (travel abroad, relocation, impending transfer...)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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69 participants in 2 patient groups, including a placebo group

bNAbs

Active Comparator group

Description:

ART plus dual long-acting (LS) broadly neutralising antibodies (bNAbs) infusion at HIV-1 primary HIV-1 infection, during 52 weeks minimum, followed by and Antiretroviral Treatment Interruption (ATI).

Treatment:

Drug: Recombinant human monoclonal antibody (bNAbs)

Placebo

Placebo Comparator group

Description:

ART plus placebo (saline solution) at HIV-1 primary HIV-1 infection, during 52 weeks minimum, followed by and Antiretroviral Treatment Interruption (ATI).

Treatment:

Drug: Placebo