Evaluation of the Safety and the Tolerability of a Combination of Two HIV Inducers in Patients With Undetectable Viral Load

• Status: Not yet recruiting
• Trial end date: 2026-02-28
• Target enrollment: 0
• Participant gender: Male

Summary

The ANRS 171 SYNACTHIV trial is an international multicenter pilot open label phase I trial. This trial will evaluate new procedures in LRA administration in 3 successive cohorts. In case of grade 3 to grade 5 adverse events, the inclusions and treatments will be (but not in a definitive manner) discontinued until the DSMB will conclude that the event was unrelated. Enrolment in cohort 2 then in cohort 3 will start only if no clinical grade 3 to grade 5 adverse event related to the LRAs occurs in the previous cohort.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases
• Collaborator: INSERM SC10-US19
• Treatments: Decitabine; Romidepsin

Criteria

Inclusion Criteria:

• Man aged 18-69 years;

• Man with documented infection with sub-type B HIV-1;

• On cART since more than 48 months before pre- screening and at a stable regimen for at least 2 months 27 before pre-screening and until inclusion;

• HIV plasma viral load persistently < the threshold (of the local test used) and undetectable during the 12 months prior to pre-screening and until inclusion, with no blip* allowed (a minimum of 2 VL results are necessary, including the pre-screening value). * blip is defined as 50cp ≤HIV viral load<400 cp mL-1;

• CD4+ T-cells count nadir ≥ 200 cells per mm3 documented in the medical file;

• CD4+ T-cells count ≥ 500 cells per mm3 for at least 12 months before pre-screening and until inclusion;

• EBV viral load < 1000 cp.mL-1, CMV viral load < 10000 cp mL-1;

• HIV DNA >2.3 log copies /106 cells at pre-screening visit

• HIV-1 positive reactivation at screening visit

• Complete COVID-19 vaccine scheme (according to national recommendations).

• Able and willing to comply with study visits and procedures as per protocol;

• Able to understand, sign and date the written voluntary informed consent form at the pre screening visit prior to any protocol-specific procedures.

Regulatory criteria (French regulations):

• Free, informed and written consent signed by the person and the investigator (at the latest on the day of pre-screening and before any investigation carried out as part of the trial) (Article L1122-1-1 of the Code of Public Health).

• An affiliated person beneficiary of a social security scheme (Article L1121-11 of the Public Health Code) (Aide Médicale d'Etat or AME is not a social security scheme).

• A person who agrees to be registered in the national file of persons who lend themselves to biomedical research (article L1121-16 of the Public Health Code).

Regulatory criteria (Belgian regulations):

• Free, informed and written consent signed by the person and the investigator (at the latest on the day of pre-screening and before any investigation carried out as part of the trial) (law of 7 May 2004. article 6)

Exclusion Criteria:

• Man who want to father a child or refuse contraception (condoms) while receiving treatment and for 3 months following completion of treatment; Man with a female partner of childbearing potential who refuses to use a highly effective contraceptive method during the same period (Experimental treatment period and for 3 months following completion of experimental treatment).

• Clinically significant cardiac disease including QTc-prolongation (QTc value > 450msec);

• On PI based regimen or regimen containing NNRTI, Ritonavir or Cobicistat;

• Treated with CYP 450 inducer or inhibitor, in particular dexamethasone, carbamazepine, phenytoin, rifabutin, rifapentine and phenobarbital;

• Treated with anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation;

• Treated with warfarin or coumarin derivative;

• History of an AIDS-defining clinical illness (based on CDC classification, appendix A4);

• Coinfection with viral hepatitis B;

• Coinfection with viral hepatitis C;

• Active malignancy that may require chemotherapy or radiation therapy;

• Any significant acute medical illness in the 8 weeks prior to pre-screening and until inclusion;

• Haematological or biochemical laboratory parameters at pre-screening and screening :

Hemoglobin (1.2), Partial Thromboplastin Time (>ULN), Total serum Creatinine (>ULN), urea (ULN) uric acid (>ULN), glycemia (ULN), total serum bilirubin (>ULN), Alkaline Phosphatase (ALP) (>ULN), AST-ALT (>ULN), gammaglutamyl transferase (GGT) (>ULN), lipasemia (>ULN), LDH (>ULN) , Ionogram: Na (ULN), K (ULN), Ca ( >ULN), Mg (ULN), CRP (>ULN), albumin (ULN), CPK (>ULN);

• Liver insufficiency (Child Pugh score >5);

• Kidney insufficiency (Estimation of glomerular filtration<60mL/mn/1,73m2 ; evaluation with CKDepi formula, according to the 2012 French Haute autorité de santé recommandations);

• Participant under guardianship or curatorship or deprived of their liberty by a judicial or administrative decision

• Participant potentially inable to follow the protocol requirements (e.g. comprehension of the study requirements, ability to understand and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits).

• Participating to another interventional study or still in an exclusion period from another clinical trial (category 1 or 2 study for France);

• Planning to participate in a study within 3 months after the end of the present trial.