ANRS 12372 MODERATO Study

NCT04022967 | Unknown Phase 3 DMC

• 1 other identifier: ANRS 12372 MODERATO
• Study Type: interventional
• Target: 480
• Locations: 3 countries
• Sites: 5

Brief Summary

MODERATO is a phase III, open-label, randomized, multicenter, non-inferiority trial conducted in West and Central Africa (Cameroon, Côte d'Ivoire, Burkina Faso). HIV-1 infected adults receiving first line ART with TDF+XTC+EFV or DTG+XTC+TDF virologically suppressed will be recruited and followed during 100 weeks. The objective is to assess the non-inferiority of a strategy consisting of switching to a dual maintenance therapy (DTG+3TC or ATV/r+3TC), comparing to WHO standard first line regimen (TDF+3TC+EFV or DTG+3TC+TDF), in terms of virological success at 96 weeks

Conditions

HIV-1-infection

Keywords

Africa; Antiretroviral Treatment; HIV-1; Adults; Dual maintenance therapy; Dolutegravir; Atazanavir

Outcome Measures

Primary Outcomes (1)

• The treatment success, as defined by using the FDA snapshot algorithm

  Success : The proportion of patients who are still continuing the assigned strategy and whose last available plasma HIV-1 RNA in the the window analysis is \<50 copies/ml at the end of the window analysis. Failure : patients who have discontinued the assigned strategy or whose last available plasma HIV-1 RNA in the window analysis (90 to 102 weeks) is ≥ 50 copies/ml or with no available HIV-1 RNA in the window analysis

  90 to 102 weeks

Secondary Outcomes (22)

• Failure combined endpoint

  Between Day 0 and Week 96

• Plasma HIV-1 RNA

  Between Day 0 and Week 96

• Virological success

  Between Day 0 and Week 96

• CD4 lymphocyte

  Between Day 0 and Week 96

• Virological failure and new resistance mutations

  Week 48 and Week 96

Study Arms (3)

Arm 1 : Dual maintenance therapy DTG+3TC

EXPERIMENTAL

Drug: dolutegravir; Drug: Lamivudine

Arm 2 : Dual maintenance therapy ATV/r+3TC

EXPERIMENTAL

Drug: atazanavir boosted with ritonavir; Drug: Lamivudine

Arm 3 : Reference triple therapy TDF+3TC+EFV or DTG+3TC+TDF

ACTIVE COMPARATOR

Drug: tenofovir + lamivudine +efavirenz or dolutegravir + lamivudine + tenofovir

Interventions

dolutegravir DRUG

One daily tablet (50mg) during 96 weeks

Arm 1 : Dual maintenance therapy DTG+3TC

atazanavir boosted with ritonavir DRUG

One daily tablet with atazanavir (300 mg) boosted with ritonavir (100 mg) during 96 weeks

Arm 2 : Dual maintenance therapy ATV/r+3TC

tenofovir + lamivudine +efavirenz or dolutegravir + lamivudine + tenofovir DRUG

One daily tablet with tenofovir 245 mg + lamivudine (300 mg) + efavirenz (400 mg) during 96 weeks OR One daily tablet with dolutegravir 50 mg + lamivudine (300 mg) + tenofovir (300 mg) during 96 weeks

Arm 3 : Reference triple therapy TDF+3TC+EFV or DTG+3TC+TDF

Lamivudine DRUG

One daily tablet (300mg) during 96 weeks

Arm 1 : Dual maintenance therapy DTG+3TC; Arm 2 : Dual maintenance therapy ATV/r+3TC

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection
• Age of legal majority
• Start first-line ART with non-nucleotide reverse transcriptase inhibitors including TDF+XTC+EFV for at least two years without a past history of virological failure, OR
• Be on TDF+XTC+EFV for at least two years then DTG+XTC+TDF without a past history of virological failure, OR
• Be on DTG+XTC+TDF (1st line regimen) for at least two years without a past history of virological failure
• Absence of past history of virological failure (viral load above the threshold corresponding to the test used); two blips between 50 and 200 copies/ml are allowed.
• Women with pregnancy potential are required to use an effective contraceptive method throughout the study follow up.
• Signed informed consent

You may not qualify if:

• HIV-2 infection or HIV-1+2 infection
• CD4 nadir \<100 cells/mm3
• Ongoing active Tuberculosis
• Ongoing severe opportunistic infection
• Ongoing chemotherapy or immunotherapy
• Grade \> 2 hemoglobin, neutrophil or platelet disorder
• ALT≥ 3 times the upper limit of normal value
• Creatinine clearance \< 50 ml/min (CKD-EPI)
• Allergy to a trial drugs or drug component
• Ongoing pregnancy or Refusal of contraception
• Patient at risk of non-compliance
• Ongoing treatment with a drug that should not be associated with one of the drugs used in the study (cf appendix E page 77)
• Any symptoms or biological findings suggestive of a systemic disorder (renal, hepatic, cardiovascular, pulmonary) or other medical conditions that may interfere with the interpretation of test results or jeopardize the health of patients

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Mylan Laboratories: collaborator

Study Sites (5)

Hôpital de jour, Service des maladies infectieuses, CHU Sourô Sanou

Bobo-Dioulasso, Burkina Faso

Location

Service de médecine interne, CHU Yalgado Ouédraogo

Ouagadougou, Burkina Faso

Location

Service des Maladies Infectieuses, Hôpital du jour, Hôpital Central

Yaoundé, Cameroon

Location

Centre de Prise en Charge et de Formation (CePReF), Association ACONDA

Abidjan, Côte d’Ivoire

Location

Service des Maladies Infectieuses et Tropicales (SMIT), CHU de Treichville

Abidjan, Côte d’Ivoire

Location

Related Links

• Sponsor site
• Related Info

MeSH Terms

Interventions

dolutegravir; Ritonavir; Tenofovir; Lamivudine

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Serge P. Eholié, MD, MSc, Pr

  Service des Maladies Infectieuses et Tropicales, CHU de Treichville, Abidjan, Côte d'Ivoire

  PRINCIPAL INVESTIGATOR

• Roland Landman, MD

  Institut de Médecine et d'Epidémiologie Appliquée - Hôpital Bichat Claude Bernard, Paris, France

  PRINCIPAL INVESTIGATOR

• Xavier Anglaret, MD, PhD

  Inserm 1219, Université de Bordeaux, France

  STUDY DIRECTOR

• Pierre-Marie Girard, MD, PhD

  Infectious Diseases Department, University Hospital Saint Antoine, Paris, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: July 17, 2019
• Study Start: September 21, 2020
• Primary Completion: February 5, 2025
• Study Completion: February 5, 2025
• Last Updated: September 6, 2023

Record last verified: 2023-05

Locations

CA (1); CÔ (2); BU (2)