Dolutegravir + Rilpivirine Switch Study (DORISS)

NCT ID: NCT02069834

Last Updated: 2015-08-28

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2017-10-31

Brief Summary

The primary objective of the study is to evaluate the capacity of Dolutegravir + Rilpivirine vs. continued triple combination HAART to maintain plasma HIV RNA ≤ 50 copies/ml throughout 24 weeks in patients with plasma HIV RNA ≤ 50 copies/mL for at least 2 years under conventional HAART (2 NNRTI + 3rd agent).

The main secondary objectives are the following:

• % of virologic success (plasma viral load ≤ 50 copies/mL) at W24 and W48
• % of patients who maintain a plasma viral load ≤ 50 copies / ml from D0 to W48
• % of virological failure defined by two consecutive plasma viral load > 50 copies/mL
• Profile of genotypic resistance in case of virological failure.

The trial will be conducted according to the design below, in 3 steps:

• Step 1: enrollment of 80 patients (40 in each arm)
• Step 2: enrollment on hold until W16 data from the 40 patients enrolled in the intervention arm have been analyzed.
• Step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/mL from D0 to W16 is significantly > 70%, which translates in a maximum of 6 virologic failures.

Conditions

HIV Infection; HAART-treated; Virologically Controlled

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 (intervention)

Dolutegravir 50 mg/d + Rilpivirine 25 mg/d qd orally (intake during a meal)

Group Type: EXPERIMENTAL

Arm 1 (intervention)

Intervention Type: DRUG

Dolutegravir 50 mg/j + Rilpivirine 25 mg/j qd orally (intake during meal)

Arm 2 (control)

Continuation of existing HAART at the time of randomization

Group Type: ACTIVE_COMPARATOR

Arm 2 (control)

Intervention Type: DRUG

Continuation of existing HAART at the time of randomization

Interventions

Arm 1 (intervention)

Dolutegravir 50 mg/j + Rilpivirine 25 mg/j qd orally (intake during meal)

Intervention Type: DRUG

Arm 2 (control)

Continuation of existing HAART at the time of randomization

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• HIV-1 infection
• Treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, or 1 NNRTI, or INI), unchanged for > 6 months, Intra-class substitution within past 6 months is not considered as a treatment change.
• Plasma HIV-RNA ≤ 50 copies/mL for > 2 years
• CD4 cell count > 350/mm3 for > 6 months
• No prior virologic failure under an NNRTI-containing or an INSTI-containing ART regimen
• No NNRTI mutation on pre-ART genotype (if no pre-ART genotype available: no NNRTI mutation on DNA genotype at screening) among the following: K101E/P, E138A/G/K/Q/R/S, V179L, Y181C/I/V, Y188L, H221Y, M230I/L/V, L100I + K103N/S, L100I +K103R +V179D.
• No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S
• Negative HBs Ag
• Informed consent form signed by patient and investigator
• A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study
• Patient covered with health insurance
• Effective contraception

Exclusion Criteria

• HIV-2 infection
• Dialysis or severe renal failure (creatinine clearance < 30 ml/min)
• History of decompensated liver disease
• History of HIV-associated neurocognitive disorders
• AST or ALT > 5 x ULN
• Positive HBc Ac and negative HBs Ac
• Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug
• Current pregnancy or breastfeeding
• Patient involved in another research that precludes enrolment in another trial
• Patient under guardianship, or deprived of liberty by a court or administrative decision.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU Guadeloupe

Point-a-pitre, Guadeloupe, France

CHU de Fort de France

Fort de France, Martinique, France

Chu Jean Minjoz

Besançon, , France

Hôpital Avicenne

Bobigny, , France

Hôpital Jean Verdier

Bondy, , France

CHU de Bordeaux

Bordeaux, , France

CHU de DIJON

Dijon, , France

CHD La Roche sur Yon

La Roche-sur-Yon, , France

CHU Kremlin Bicêtre

Le Kremlin-Bicêtre, , France

Hôpital Perpetuel Secours

Levallois-Perret, , France

CHU de Nantes

Nantes, , France

CHU Hôtel Dieu Paris

Paris, , France

Hôpital La Pitié Salpêtrière

Paris, , France

Hôpital Necker - enfants Malades

Paris, , France

Hôpital Saint Louis

Paris, , France

CHU BICHAT - Claude Bernard

Paris, , France

Hôpital Européen Georges Pompidou

Paris, , France

CHU de Rennes - Hôpital Pontchaillou

Rennes, , France

CH Delafontaine

Saint-Denis, , France

CHU Saint Etienne

Saint-Etienne, , France

CHU de Strasbourg

Strasbourg, , France

Hôpital FOCH

Suresnes, , France

CHU Toulouse

Toulouse, , France

CHRU de Tours

Tours, , France

CHU de Nancy

Vandœuvre-lès-Nancy, , France

Countries

France

Other Identifiers

2013-003344-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RC13_0322

Identifier Type: -

Identifier Source: org_study_id