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

April 12, 2024 updated by: ANRS, Emerging Infectious Diseases

A Randomised Phase II Placebo-controlled Trial of Antiretroviral Therapy (ART) Plus Dual Long-acting HIV-specific Broadly Neutralising Antibodies (bNAbs) vs ART Plus Placebo During Primary HIV-1 Infection to Study the Impact on Post-treatment HIV Control.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

69

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Bobigny, France, 93000
        • Not yet recruiting
        • Hôpial Avicenne - SMIT
        • Principal Investigator:
          • Olivier Bouchaud
        • Contact:
      • Clamart, France, 92140
        • Not yet recruiting
        • Hôpital Antoine Béclère
        • Principal Investigator:
          • Sophie Abgrall
        • Contact:
      • Clichy, France, 92110
        • Not yet recruiting
        • Hôpital Beaujon - Service de médecine interne
        • Contact:
        • Principal Investigator:
          • Agnès Villemant Ululag
      • Créteil, France, 94010
      • Garches, France, 92380
        • Not yet recruiting
        • Hôpital Raymond Poincaré - SMIT
        • Principal Investigator:
          • Pierre De Truchis
        • Contact:
      • Le Kremlin-Bicêtre, France, 94275
        • Not yet recruiting
        • Hôpital Bicêtre - HdJ - Médecine interne
        • Principal Investigator:
          • Cécile Goujard
        • Contact:
      • Paris, France, 75004
        • Not yet recruiting
        • Hôpital Hôtel - Dieu
        • Principal Investigator:
          • Jean-Paul Viard
        • Contact:
      • Paris, France, 75004
        • Not yet recruiting
        • Hôpital Hôtel Dieu - Service d'immunologie clinique
        • Contact:
        • Principal Investigator:
          • Laurence Weiss
      • Paris, France, 75013
      • Paris, France, 75475
        • Not yet recruiting
        • Hôpital Lariboisière - Service de médecine interne A
        • Contact:
        • Principal Investigator:
          • Pierre Sellier
      • Paris, France, 75475
        • Recruiting
        • Hôpital Saint- Louis - SMIT
        • Contact:
        • Principal Investigator:
          • Caroline Lascoux-Combe
      • Paris, France, 75571
      • Paris, France, 75743
        • Not yet recruiting
        • Hôpital Necker - SMIT
        • Principal Investigator:
          • Claudine Duvivier
        • Contact:
      • Paris, France, 75877
        • Not yet recruiting
        • Hôpital Bichat - Claude Bernard - SMIT
        • Contact:
        • Principal Investigator:
          • Jade Ghosn
      • Paris, France, 75970
      • Suresnes, France, 92151
        • Not yet recruiting
        • Centre médico chirurgical Foch - Suresnes
        • Contact:
        • Principal Investigator:
          • David Zucman
      • Villeneuve-Saint-Georges, France, 94195
        • Not yet recruiting
        • CHI Villeneuve-Saint-Georges - SMIT
        • Contact:
        • Principal Investigator:
          • Pauline Caraux Paz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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...)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: bNAbs
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).
Drug: Recombinant human monoclonal antibody (bNAbs)
  1. Initiation of combination ART (1 integrase inhibitor + 2 nucleoside analogue reverse transcriptase inhibitors) with additional dual intravenous infusions of bNAbs (3BNC117LS & 10-1074LS) between Day 7 and Day 10.
  2. Analytical treatment interruption (ATI), 52 weeks later, if good immunologic and virologic conditions.
  3. During ATI, plasma HIV-1 RNA and CD4 monitoring, for a maximum of 48 weeks.
  4. ART resumption, if participant encounters at least one ART resumption criteria.
Other Names:
  • 10-1074-LS and 3BNC117-LS
Placebo Comparator: Placebo
ART plus placebo (saline solution) at HIV-1 primary HIV-1 infection, during 52 weeks minimum, followed by and Antiretroviral Treatment Interruption (ATI).
Drug: Placebo
  1. Initiation of combination ART (1 integrase inhibitor + 2 nucleoside analogue reverse transcriptase inhibitors) with additional dual intravenous infusions of placebo (saline solution) between Day 7 and Day 10.
  2. Analytical treatment interruption (ATI), 52 weeks later, if good immunologic and virologic conditions.
  3. During ATI, plasma HIV-1 RNA and CD4 monitoring, for a maximum of 48 weeks.
  4. ART resumption, if participant encounters at least one ART resumption criteria.
Other Names:
  • Saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants with plasma HIV-1 RNA below 400 cp/mL 24 weeks following ATI (W24 ATI), in the confirmed absence of ART.
Time Frame: at Week 24 of antiretroviral treatment interruption period (ATI)
These participants will be considered as post-treatment controllers.
at Week 24 of antiretroviral treatment interruption period (ATI)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tolerance of bNAbs infusion : Number of clinical and biological adverse event (AE)
Time Frame: from date of inclusion to the last follow-up visit date, up to 148 weeks
Number of clinical and biological AE during follow-up. Abnormal laboratory values will be identified as those outside values defined by the DAIDS scale
from date of inclusion to the last follow-up visit date, up to 148 weeks
Tolerance of bNAbs infusion : Nature and Grade of clinical and biological AE
Time Frame: from date of inclusion to the last follow-up visit date, up to 148 weeks
Grade of clinical and biological adverse during follow-up. The intensity of all AE (serious and non-serious) will be graded using the DAIDS AE Grading Table Corrected Version 2.1-July 2017
from date of inclusion to the last follow-up visit date, up to 148 weeks
Tolerance of bNAbs infusion : Time of clinical and biological adverse event (AE)
Time Frame: from date of inclusion to the last follow-up visit date, up to 148 weeks
from date of inclusion to the last follow-up visit date, up to 148 weeks
Proportion of participants resuming ART within the first 24 weeks of ART interruption, according to the reason for resuming.
Time Frame: at Week 24 of antiretroviral treatment interruption period (ATI)
at Week 24 of antiretroviral treatment interruption period (ATI)
Time to potential ART resumption for non-controllers.
Time Frame: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption date, assessed up to 48 weeks following ATI
from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption date, assessed up to 48 weeks following ATI
Clinical and immulogical criteria during follow-up: Proportion of participants with clinical symptoms.
Time Frame: during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
Clinical and immulogical criteria during follow-up: Evolution of CD4, CD8 (levels and %) and CD4/CD8 ratio.
Time Frame: during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
Clinical and immulogical criteria during follow-up: Evolution of inflammation markers levels.
Time Frame: biological parameters levels during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
physiological parameters levels will be studied: IP10, TGFβ, IL-7, IL-10, IL-12, IL-15, IL-18, Citrulline, sCD14, sCD163, TNF-α
biological parameters levels during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
Immulogical criteria : Changes in the magnitude and quality of HIV-specific T cell responses and humoral responses.
Time Frame: physiological parameters levels during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
physiological parameters levels will be studied: frequency and functionality of T cells responding to HIV peptides measured by intracellular cytokine staining, surface expression of activation and differentiation markers, HIV suppressive capacity upon co-culture with autologous infected cells
physiological parameters levels during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
Virological criteria during follow-up: Plasma HIV-1 RNA and HIV-1 DNA level and cell-associated HIV RNA transcripts changes.
Time Frame: during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
Virological criteria : Proportion of participant with plasma HIV-1 RNA < 50 cp/mL at 12- and 24-weeks following ART interruption.
Time Frame: at Week 12 and Week 24 of antiretroviral treatment interruption period (ATI)
at Week 12 and Week 24 of antiretroviral treatment interruption period (ATI)
Virological criteria : Cumulative plasma viremia during ART interruption.
Time Frame: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
Virological criteria : in case of ART resumption, time from date of ART interruption begining to date of first HIV-1 RNA ≥ 50 copies/mL
Time Frame: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
Virological criteria : in case of ART resumption, proportion of participant with plasma HIV-1 RNA < 50 copies/mL within 24 weeks of ATI.
Time Frame: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
Virological criteria : Evolution of total HIV-1 DNA and cell-associated HIV-1 RNA by US q-PCR and predictive value on post- ART interruption evolution.
Time Frame: during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
Virological criteria : Evolution of detection proportion and level of cell-associated HIV-1 RNA.
Time Frame: during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
Virological criteria : Qualitative and quantitative changes in the persistent viral reservoir.
Time Frame: physiological parameters levels during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
physiological parameters levels will be studied: total cell associated HIV-DNA, integrated HIV-DNA, proportion of replication competent vs defective proviruses
physiological parameters levels during all ART period (from Day 0 to Week 52 ARV), during all ATI period (from Day 0 ATI to Day 0 ART Resumption) and during ART resumption period (from Day 0 to Week 24 ART Resumption)
Dosages of bNAbs performed during follow-up.
Time Frame: during ART follow-up (Week 1,Week 12, Week 24, Week 36), and antiretroviral treatment interruption period (Day 0, Week 12, Week 24)
during ART follow-up (Week 1,Week 12, Week 24, Week 36), and antiretroviral treatment interruption period (Day 0, Week 12, Week 24)
Criteria related to the risk of HIV-1 transmission : Proportion of participants reporting to use condoms during sexual intercourses
Time Frame: from date of inclusion to the last follow-up visit date, up to 148 weeks
from date of inclusion to the last follow-up visit date, up to 148 weeks
Criteria related to the risk of HIV-1 transmission : Proportion of participants reporting to have proposed PrEP at their partners.
Time Frame: from date of inclusion to the last follow-up visit date, up to 148 weeks
from date of inclusion to the last follow-up visit date, up to 148 weeks
Social sciences criteria : Proportion of patients satisfied with their participation and the associated factors
Time Frame: from date of inclusion to the last follow-up visit date, up to 148 weeks
from date of inclusion to the last follow-up visit date, up to 148 weeks
Social sciences criteria : Impact of the participation in the trial on participant quality of life and quality of sexual life
Time Frame: from date of inclusion to the last follow-up visit date, up to 148 weeks
Through statistical analyses of some self-administered questionnaires items (in particular the SF12.v2 scale for quality of life) and thematic analyses of semi-directive individual interviews we will highlight the impact of the participation in the trial.
from date of inclusion to the last follow-up visit date, up to 148 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ANRS, Emerging Infectious Diseases

Collaborators

Institut Pasteur
Rockefeller University

Investigators

  • Principal Investigator: Cécile Goujard, Pr, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 11, 2024

Primary Completion (Estimated)

December 10, 2026

Study Completion (Estimated)

December 10, 2028

Study Registration Dates

First Submitted

January 3, 2022

First Submitted That Met QC Criteria

March 18, 2022

First Posted (Actual)

March 29, 2022

Study Record Updates

Last Update Posted (Estimated)

April 15, 2024

Last Update Submitted That Met QC Criteria

April 12, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 176 RHIVIERA-02

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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