10-1074-LS for HIV-1 infection|HIV

Inclusion criteria

• {"criterion_text":"- Participant with confirmed primary HIV-1 infection (PI) diagnostic, symptomatic or asymptomatic, corresponding to one of the situations bellow: o\tNegative ELISA test (non-dissociated test) or ELISA Ac-/p24- and positive HIV-1 RNA (confirmed by a second positive HIV-1 RNA), o\tELISA test Ac-/p24+ (confirmed by a positive HIV-1 RNA), o\tPositive ELISA test (non-dissociated test) or ELISA Ac+/p24+ or ELISA Ac+/p24- and WB-HIV-1 [0-5] band(s) or IB-HIV-1 [0-3] band(s) (confirmed by a positive HIV-1 RNA). Any result achieved in the previous 30 days of inclusion visit will be considered.\n- HIV-1 RNA greater than or equal to 10 000 copies/mL;\n- Aged 18 years or more, and less than 70 years, at the time of consent;\n- Participant who accepts the use of an effective method of contraception from the inclusion until the end of the follow-up in the trial (minimum 52 weeks). For men and trans women, his also applies to sperm donation;\n- For women or trans men: o\tnegative plasmatic beta human chorionic gonadotropin (β-HCG) pregnancy test, o\tagree not to seek pregnancy including through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit,\n- Informed and written signed consent;\n- Participant with regular health insurance (AME is not considered as a regular health insurance);\n- Participant accepting additional constraints and: o\twilling to travel to one of the IMP administration centers (between D7ARV and D10ARV), o\twilling to interrupt ART,\n- Agreement to be vaccinated against COVID-19 before ATI, according to current recommendations.\n- Antiretroviral treatment not initiated prior to inclusion visit, with the exception of pre- or post-exposure prophylaxis ;"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Proportion of participants with plasma HIV-1 RNA below 400 cp/mL 24 weeks following ATI, in the confirmed absence of ART. These participants will be considered as post-treatment controllers (PTC).","definition_or_measurement_approach":"Measured as proportion of participants with plasma HIV-1 RNA < 400 copies/mL at 24 weeks after analytic treatment interruption (ATI) in confirmed absence of ART."}

Secondary endpoints

• {"endpoint_text":"- Tolerability of intravenous infusions of bNAbs: number, grade, reason and time of clinical and biological adverse event (AE): o\tDuring ART, o\tDuring overall follow-up,","definition_or_measurement_approach":"Number, grade, reason and timing of clinical and biological AEs recorded during ART and overall follow-up."}
• {"endpoint_text":"- Proportion of participants resuming ART within the first 24 weeks of ATI, according to the reason for resuming;","definition_or_measurement_approach":"Proportion of participants who restart ART within first 24 weeks of ATI, stratified by reason for resumption."}
• {"endpoint_text":"- Time to potential ART resumption for non-controllers;","definition_or_measurement_approach":"Time from ATI start to ART resumption for participants not controlling viremia."}
• {"endpoint_text":"- Clinical and immulogical criteria, during ART (D0 to W52ARV (or W64ARV or W76ARV)), ATI (from D0ATI) and potential ART resumption (from D0Res to W24Res); o\tProportion of participants with clinical symptoms, o\tEvolution of CD4, CD8 (levels and %) and CD4/CD8 ratio, o\tEvolution of inflammation markers levels","definition_or_measurement_approach":"Clinical symptoms proportion and longitudinal measures of CD4/CD8 counts and ratio and inflammatory marker levels across specified time windows."}
• {"endpoint_text":"- Virological criteria : o\tPlasma HIV-1 RNA and HIV-1 DNA level and cell-associated HIV RNA transcripts changes during ART (D0 to W52ARV (or W64ARV or W76ARV)), ATI (from D0ATI) and potential ART resumption (from D0Res to W24Res), o\tProportion of participant with plasma HIV-1 RNA < 50 cp/mL at 12- and 24-weeks following ATI, o\tCumulative plasma viremia during ATI,","definition_or_measurement_approach":"Longitudinal plasma HIV-1 RNA, HIV-1 DNA and cell-associated RNA measurements; proportion with VL <50 cp/mL at 12 and 24 weeks post-ATI; cumulative viremia during ATI."}
• {"endpoint_text":"- Virological criteria : o\tIn case of ART resumption: \tTime from date of ATI begining to date of first VL ≥ 50 copies/mL, \tProportion of participant with plasma HIV-1 RNA < 50 copies/mL within 24 weeks of ART, o\tEvolution of total HIV-1 DNA and cell-associated HIV-1 RNA by US q-PCR and predictive value on post-ATI evolution, o\tEvolution of detection proportion and level of cell-associated HIV-1 RNA, oQualitative and quantitative changes in the persistent viral reservoir","definition_or_measurement_approach":"Time to first VL ≥50 cp/mL post-ATI, proportion achieving VL <50 within 24 weeks after ART resumption; ultrasensitive qPCR measures of HIV reservoir and related analyses."}
• {"endpoint_text":"- Virological criteria :Evolution of total HIV-1 DNA and cell-associated HIV-1 RNA by US q-PCR and predictive value on post-ATI evolution, o Evolution of detection proportion and level of cell-associated HIV-1 RNA, o Qualitative and quantitative changes in the persistent viral reservoir,","definition_or_measurement_approach":"Ultrasensitive qPCR quantification of total HIV-1 DNA and cell-associated RNA; assessment of predictive value for post-ATI outcomes."}
• {"endpoint_text":"- Immunological criteria : o\tChanges in the magnitude and quality of HIV-specific T cell responses and humoral responses after infusions of bNAbs (W1ARV) and after ATI,","definition_or_measurement_approach":"Measures of HIV-specific T-cell and humoral response magnitude and quality pre- and post-infusion and post-ATI."}
• {"endpoint_text":"- Pharmacological criteria : o\tDosages of bNAbs performed after infusions (D0 to end of ATI period), o\tDosages of ARV drugs performed during ATI (D0ATI to W24ATI)),","definition_or_measurement_approach":"Pharmacokinetic assays quantifying bNAb concentrations post-infusion and ARV drug levels during ATI."}
• {"endpoint_text":"- Criteria related to the risk of HIV-1 transmission: o\tProportion of participants reporting to use condoms during sexual intercourse during follow-up, o\tProportion of participants reporting to have proposed PrEP at their partners during ATI during follow-up,","definition_or_measurement_approach":"Self-reported condom use and proposals of PrEP to partners during follow-up."}
• {"endpoint_text":"- Social sciences criteria : o\tProportion of patients satisfied with their participation and the associated factors, o\tImpact of the participation in the trial on participant quality of life and quality of sexual life.","definition_or_measurement_approach":"Questionnaire-based measures of satisfaction and quality-of-life/sexual quality-of-life assessments."}

France

Earliest CTIS Part Ii Submission Date

30-09-2024

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

556

Number Of Sites

18

Number Of Participants

69

Primary sponsor

Full Name

ANRS Maladies Infectieuses Emergentes

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France