Clinical trial NCT05300035: Phase II Trial of ART + Dual bNAbs vs. ART + Placebo During Primary HIV-1 Infection-impact on Post-ART Control
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HIV/AIDS and Infections
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Rockefeller University
name: Institut Pasteur
First posted: 2022-03-29
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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...)

Primary outcomes:
measure: Proportion of participants with plasma HIV-1 RNA below 400 cp/mL 24 weeks following ATI (W24 ATI), in the confirmed absence of ART.
timeFrame: at Week 24 of antiretroviral treatment interruption period (ATI)
Secondary outcomes:
measure: Tolerance of bNAbs infusion : Number of clinical and biological adverse event (AE)
timeFrame: from date of inclusion to the last follow-up visit date, up to 148 weeks
measure: Tolerance of bNAbs infusion : Nature and Grade of clinical and biological AE
timeFrame: from date of inclusion to the last follow-up visit date, up to 148 weeks
measure: Tolerance of bNAbs infusion : Time of clinical and biological adverse event (AE)
timeFrame: from date of inclusion to the last follow-up visit date, up to 148 weeks
measure: Proportion of participants resuming ART within the first 24 weeks of ART interruption, according to the reason for resuming.
timeFrame: at Week 24 of antiretroviral treatment interruption period (ATI)
measure: Time to potential ART resumption for non-controllers.
timeFrame: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption date, assessed up to 48 weeks following ATI
measure: Clinical and immulogical criteria during follow-up: Proportion of participants with clinical symptoms.
timeFrame: 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)
measure: Clinical and immulogical criteria during follow-up: Evolution of CD4, CD8 (levels and %) and CD4/CD8 ratio.
timeFrame: 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)
measure: Clinical and immulogical criteria during follow-up: Evolution of inflammation markers levels.
timeFrame: 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)
measure: Immulogical criteria : Changes in the magnitude and quality of HIV-specific T cell responses and humoral responses.
timeFrame: 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)
measure: Virological criteria during follow-up: Plasma HIV-1 RNA and HIV-1 DNA level and cell-associated HIV RNA transcripts changes.
timeFrame: 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)
measure: Virological criteria : Proportion of participant with plasma HIV-1 RNA < 50 cp/mL at 12- and 24-weeks following ART interruption.
timeFrame: at Week 12 and Week 24 of antiretroviral treatment interruption period (ATI)
measure: Virological criteria : Cumulative plasma viremia during ART interruption.
timeFrame: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
measure: Virological criteria : in case of ART resumption, time from date of ART interruption begining to date of first HIV-1 RNA ≥ 50 copies/mL
timeFrame: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
measure: Virological criteria : in case of ART resumption, proportion of participant with plasma HIV-1 RNA < 50 copies/mL within 24 weeks of ATI.
timeFrame: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI
measure: 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.
timeFrame: 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)
measure: Virological criteria : Evolution of detection proportion and level of cell-associated HIV-1 RNA.
timeFrame: 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)
measure: Virological criteria : Qualitative and quantitative changes in the persistent viral reservoir.
timeFrame: 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)
measure: Dosages of bNAbs performed during follow-up.
timeFrame: during ART follow-up (Week 1,Week 12, Week 24, Week 36), and antiretroviral treatment interruption period (Day 0, Week 12, Week 24)
measure: Criteria related to the risk of HIV-1 transmission : Proportion of participants reporting to use condoms during sexual intercourses
timeFrame: from date of inclusion to the last follow-up visit date, up to 148 weeks
measure: Criteria related to the risk of HIV-1 transmission : Proportion of participants reporting to have proposed PrEP at their partners.
timeFrame: from date of inclusion to the last follow-up visit date, up to 148 weeks
measure: Social sciences criteria : Proportion of patients satisfied with their participation and the associated factors
timeFrame: from date of inclusion to the last follow-up visit date, up to 148 weeks
measure: Social sciences criteria : Impact of the participation in the trial on participant quality of life and quality of sexual life
timeFrame: from date of inclusion to the last follow-up visit date, up to 148 weeks
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpial Avicenne - SMIT
city: Clamart
country: France
facility: Hôpital Antoine Béclère
city: Clichy
country: France
facility: Hôpital Beaujon - Service de médecine interne
city: Créteil
country: France
facility: CHI Créteil - HdJ
city: Garches
country: France
facility: Hôpital Raymond Poincaré - SMIT
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre - HdJ - Médecine interne
city: Paris
country: France
facility: Hôpital Hôtel - Dieu
city: Paris
country: France
facility: Hôpital Hôtel Dieu - Service d'immunologie clinique
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière - SMIT
city: Paris
country: France
facility: Hôpital Lariboisière - Service de médecine interne A
city: Paris
country: France
facility: Hôpital Saint- Louis - SMIT
city: Paris
country: France
facility: Hôpital Saint-Antoine - SMIT
city: Paris
country: France
facility: Hôpital Necker - SMIT
city: Paris
country: France
facility: Hôpital Bichat - Claude Bernard - SMIT
city: Paris
country: France
facility: Hôpital Tenon - SMIT
city: Suresnes
country: France
facility: Centre médico chirurgical Foch - Suresnes
city: Villeneuve-Saint-Georges
country: France
facility: CHI Villeneuve-Saint-Georges - SMIT
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Cécile Goujard, Pr
role: PRINCIPAL_INVESTIGATOR
References: