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

NCT05230368 | Completed Phase 1 DMC

• 1 other identifier: ANRS 171 SYNACTHIV
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The ANRS 171 SYNACTHIV trial is a monocenter 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.

Conditions

HIV-1-infection, Subtype b

Outcome Measures

Primary Outcomes (1)

• Incidence of Serious Adverse Events (SAE) and severe clinical or biological adverse events (AE) related to the study drugs

  Incidence of Serious Adverse Events (SAE) and severe clinical or biological adverse events (AE) related to the study drugs, , according to CTCAE scale, per patient

  within 2 weeks after the last injection for each patient

Secondary Outcomes (7)

• Incidence of clinical and biological adverse events (AE) of all grades

  through study completion, an average of 4 years

• Efficacy of the treatment on the HIV reservoir

  At pre-screening, before the first dose of each cycle (day 1), 1 hour following each romidepsine administration (day 4, day 11, day 18), at the end of each cycle (day 32), at each follow-up visit (Follow-up days 28, 84, 140, 364) of each cohort.

• Blood concentration of decitabine and romidepsin after injection

  day 1, day 4, day 11; day 18 of cycle 1

• Capacity of latently-infected cells to be reactivated

  at pre-screening, at day 32 of each cycle of treatment, at follow-up visit day 140 of each cohort

• Increase in viral load

  at pre-screening and at day 1 of each cycle (prior decitabin treatment), day 25 and day 32, and at each follow-up visit ((day 28, day 84, day 140, day 364)

Study Arms (3)

1 cycle of treatment (Cohort 1 = 5 patients)

EXPERIMENTAL

* decitabine (5mg/m²) at days 1, 2, 3 * romidepsin (5mg/m²) at days 4, 11, 18

Drug: Decitabine cycle 1; Drug: Romidepsin cycle 1

2 cycles of treatment (Cohort 2 = 5 patients)

EXPERIMENTAL

* decitabine (5mg/m²) at days 1, 2, 3, 35, 36, 37 * romidepsin (5mg/m²) at days 4, 11, 18, 38, 45, 52

Drug: Decitabine cycle 1; Drug: Romidepsin cycle 1; Drug: Decitabine cycle 2; Drug: Romidepsin cycle 2

4 cycles of treatment (Cohort 3 = 5 patients)

EXPERIMENTAL

* decitabine (5mg/m²) at days 1, 2, 3, 35, 36, 37, 70, 71, 72, 105, 106, 107 * romidepsin (5mg/m²) at days 4, 11, 18, 38, 45, 52, 73, 80, 87, 108, 115, 122

Drug: Decitabine cycle 1; Drug: Romidepsin cycle 1; Drug: Decitabine cycle 2; Drug: Romidepsin cycle 2; Drug: Decitabine cycle 3; Drug: Romidepsin cycle 3; Drug: Decitabine cycle 4; Drug: Romidepsin cycle 4

Interventions

Romidepsin cycle 1 DRUG

Romidepsin administration (5mg/m²) at days 4, 11, 18

1 cycle of treatment (Cohort 1 = 5 patients); 2 cycles of treatment (Cohort 2 = 5 patients); 4 cycles of treatment (Cohort 3 = 5 patients)

Decitabine cycle 2 DRUG

Decitabine administration (5mg/m²) at days 35, 36, 37

2 cycles of treatment (Cohort 2 = 5 patients); 4 cycles of treatment (Cohort 3 = 5 patients)

Romidepsin cycle 2 DRUG

Romidepsin administration (5mg/m²) at days 38, 45, 52

2 cycles of treatment (Cohort 2 = 5 patients); 4 cycles of treatment (Cohort 3 = 5 patients)

Decitabine cycle 3 DRUG

Decitabine administration (5mg/m²) at days 70, 71, 72

4 cycles of treatment (Cohort 3 = 5 patients)

Romidepsin cycle 3 DRUG

Romidepsin administration (5mg/m²) at days 73, 80, 87

4 cycles of treatment (Cohort 3 = 5 patients)

Decitabine cycle 4 DRUG

Decitabine administration (5mg/m²) at days 105, 106, 107

4 cycles of treatment (Cohort 3 = 5 patients)

Romidepsin cycle 4 DRUG

Romidepsin administration (5mg/m²) at days 108, 115, 122

4 cycles of treatment (Cohort 3 = 5 patients)

Decitabine cycle 1 DRUG

Decitabine administration (5mg/m²) at days 1, 2, 3

1 cycle of treatment (Cohort 1 = 5 patients); 2 cycles of treatment (Cohort 2 = 5 patients); 4 cycles of treatment (Cohort 3 = 5 patients)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man aged 18-69 years;
• Man with documented infection with sub-type B HIV-1;
• CD4+ T-cells count nadir ≥ 200 cells per mm3 documented in the medical file; Transient CD4+ T-cells count \< 200 cells per mm3 is allowed for a short period if the value is associated with a single isolated acute infection
• EBV viral load \< 1000 cp.mL-1, CMV viral load \< 10000 cp mL-1;
• 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.
• 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)

You may not qualify if:

• 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 (except Doravirine which is allowed), 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);
• Active coinfection with viral hepatitis B;
• Active coinfection with viral hepatitis C;
• Received any vaccination within 4 weeks prior to the first administration of the study products and plan to receive throughout the study (with the exception of influenza and COVID-19 vaccines which can be injected 4 weeks after the last administration of the study products as well as the Monkeypox vaccination that will be allowed during trial if participant becomes a contact at risk for monkeypox infection (according to national recommendations));
• Treated with sexual hormone during the administration period of the study treatments (until CXD32);
• Active malignancy that may require chemotherapy or radiation therapy;
• Haematological or biochemical laboratory parameters at pre-screening and screening : Hemoglobin (\<LLN), absolute neutrophil count (\<LLN), platelets (\<LLN), INR (\>1.2), Partial Thromboplastin Time (\>ULN); grade ≥ 2 for the following parameters: Total serum Creatinine, urea, uric acid, glycemia, total serum bilirubin, Alkaline Phosphatase (ALP) AST-ALT, gammaglutamyl transferase (GGT), lipasemia, LDH, Ionogram: Na, K, Ca, Mg, CRP, albumin, proteins, CPK;
• 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);

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• INSERM SC10-US19: collaborator

Study Sites (1)

CHU Saint-Pierre

Brussels, 1000, Belgium

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This is a monocenter pilot open label phase I trial. This trial will evaluate new procedures in LRA administration in 3 successive cohorts of 5 patients each receiving 1, 2 and 4 cycles respectively.

Study Record Dates

• First Submitted: December 23, 2021
• First Posted: February 8, 2022
• Study Start: December 14, 2022
• Primary Completion: December 11, 2025
• Study Completion: December 11, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)