ANRS 12372 MODERATO Study

NCT ID: NCT04022967

Last Updated: 2023-09-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

480 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-21

Study Completion Date

2025-02-05

Brief Summary

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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

Detailed Description

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In HIV-1 infected adults receiving first line ART with TDF+XTC+EFV or DTG+XTC+TDF virologically suppressed (viral load \< detection limit of the technique used) for at least two years: 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, in Cameroon, Côte d'Ivoire and Burkina Faso.

This is a trial including two strategies (dual maintenance therapy and triple reference therapy) and three ART regimens (DTG+3TC and ATV/r+3TC used in the maintenance strategy and TDF+3TC+EFV/ DTG+3TC+TDF used in the reference strategy).

The primary analysis will compare the two strategies. Secondary analyses will compare the three ART regimens two by two.

In order to make these secondary analyses possible, participants will be randomly assigned, at inclusion, to each of the three ART regimens (arm 1: DTG+3TC; arm 2: ATV/r+3TC; arm 3: TDF+3TC+EFV / DTG+3TC+TDF). The maintenance strategy will include arm 1 and 2. The reference strategy will include arm 3

Number of participants : 480 (160 in each ART regimen, ie 320 in the dual maintenance therapy strategy and 160 in the triple therapy reference strategy)

The primary endpoint is treatment success, as defined by using the FDA snapshot algorithm : patients who are still continuing the assigned strategy and whose last available plasma HIV-1 RNA in the the window analysis (90 to 102 weeks) is \<50 copies/ml at the end of the window analysis (90 to 102 weeks)

Conditions

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HIV-1-infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1 : Dual maintenance therapy DTG+3TC

Group Type EXPERIMENTAL

dolutegravir

Intervention Type DRUG

One daily tablet (50mg) during 96 weeks

Lamivudine

Intervention Type DRUG

One daily tablet (300mg) during 96 weeks

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

Group Type EXPERIMENTAL

atazanavir boosted with ritonavir

Intervention Type DRUG

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

Lamivudine

Intervention Type DRUG

One daily tablet (300mg) during 96 weeks

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

Group Type ACTIVE_COMPARATOR

tenofovir + lamivudine +efavirenz or dolutegravir + lamivudine + tenofovir

Intervention Type 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

Interventions

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dolutegravir

One daily tablet (50mg) during 96 weeks

Intervention Type DRUG

atazanavir boosted with ritonavir

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

Intervention Type DRUG

tenofovir + lamivudine +efavirenz or dolutegravir + lamivudine + tenofovir

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

Intervention Type DRUG

Lamivudine

One daily tablet (300mg) during 96 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV-1 infection
* Age of legal majority
* CD4 \> 200 cells/mm3 at pre-inclusion
* 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.
* At least 2 consecutive HIV-1 RNA \< 50 copies/ml within past 2 years, including HIV-1 RNA at pre-inclusion
* Women with pregnancy potential are required to use an effective contraceptive method throughout the study follow up.
* Signed informed consent

Exclusion Criteria

* HIV-2 infection or HIV-1+2 infection
* CD4 nadir \<100 cells/mm3
* Chronic Hepatitis B (HBs Ag positive in the pre-inclusion balance)
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mylan Laboratories

INDUSTRY

Sponsor Role collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Serge P. Eholié, MD, MSc, Pr

Role: PRINCIPAL_INVESTIGATOR

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

Roland Landman, MD

Role: PRINCIPAL_INVESTIGATOR

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

Xavier Anglaret, MD, PhD

Role: STUDY_DIRECTOR

Inserm 1219, Université de Bordeaux, France

Pierre-Marie Girard, MD, PhD

Role: STUDY_CHAIR

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

Locations

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

Bobo-Dioulasso, , Burkina Faso

Site Status

Service de médecine interne, CHU Yalgado Ouédraogo

Ouagadougou, , Burkina Faso

Site Status

Service des Maladies Infectieuses, Hôpital du jour, Hôpital Central

Yaoundé, , Cameroon

Site Status

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

Abidjan, , Côte d’Ivoire

Site Status

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

Abidjan, , Côte d’Ivoire

Site Status

Countries

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Burkina Faso Cameroon Côte d’Ivoire

Related Links

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Other Identifiers

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ANRS 12372 MODERATO

Identifier Type: -

Identifier Source: org_study_id

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