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

Официальное название

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.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Proportion of participants with plasma HIV-1 RNA below 400 cp/mL 24 weeks following ATI (W24 ATI), in the confirmed absence of ART. [Срок оценки: at Week 24 of antiretroviral treatment interruption period (ATI)]

Вторичные конечные точки (12)

• Tolerance of bNAbs infusion : Number of clinical and biological adverse event (AE) [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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. [Срок оценки: at Week 24 of antiretroviral treatment interruption period (ATI)]
• Time to potential ART resumption for non-controllers. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: at Week 12 and Week 24 of antiretroviral treatment interruption period (ATI)]
• Virological criteria : Cumulative plasma viremia during ART interruption. [Срок оценки: from Day 0 of antiretroviral treatment interruption period (ATI) to Day 0 of ART resumption, assessed up to 48 weeks following ATI]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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...)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Франция · 17 центров

• Hôpial Avicenne - SMIT — Bobigny
• Hôpital Antoine Béclère — Clamart
• Hôpital Beaujon - Service de médecine interne — Clichy
• CHI Créteil - HdJ — Créteil
• Hôpital Raymond Poincaré - SMIT — Garches
• Hôpital Bicêtre - HdJ - Médecine interne — Le Kremlin-Bicêtre
• Hôpital Hôtel - Dieu — Paris
• Hôpital Hôtel Dieu - Service d'immunologie clinique — Paris
• … и ещё 9 центров

Идентификаторы

NCT: NCT05300035 · ANRS 176 RHIVIERA-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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