Clinical trial NCT02069834: Dolutegravir + Rilpivirine Switch Study (DORISS)
Official title: Dolutegravir + Rilpivirine Switch Study (DORISS): Pilot and Noninferiority Trial Comparing Dolutegravir + Rilpivirine vs. Continued HAART (Highly Active Antiretroviral Therapy) in Patients With Plasma HIV RNA ≤ 50 Copies/mL for at Least 2 Years
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: HIV Infection
HAART-treated
Virologically Controlled
Keywords: Dolutegravir
Rilpivirine
PI- and NRTI- sparing ART regimen
switch study
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2014-02-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)
timeFrame: Week 16
measure: Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48
timeFrame: Week 48
measure: Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48
timeFrame: Week 48
measure: Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL
timeFrame: Week 48
measure: Measure of the profile of genotypic resistance in plasma in case of virologic failure
timeFrame: Week 48
measure: Percentage of patients who discontinued or changed the strategy of the study
timeFrame: Week 48
measure: Measure of the HIV-DNA between day 0 and week 48
timeFrame: W48
measure: Measure of CD4 lymphocytes at week 24 compared to day 0
timeFrame: Week 24
measure: Measure of CD4 lymphocytes at Week 48 compared to Day 0
timeFrame: Week 48
measure: Number of patients with adverse events of grade 2 to 4
timeFrame: Week 48
measure: Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0
timeFrame: Week 24
measure: Measure of changes in serum lipid parameters at week 48 to Day 0
timeFrame: Week 48
measure: Measure of changes in fat mass distribution at week 24 compared to Day 0
timeFrame: Week 24
measure: Measure of changes in fat mass distribution at Week 48 compared to Day 0
timeFrame: Week 48
measure: Measure of adherence to treatment at Week 24 compared to Day 0
timeFrame: Week 24
measure: Measure of adherence to treatment at Week 48 compared to Day 0
timeFrame: Week 48
measure: Measure of patient satisfaction for their treatment at Day 0
timeFrame: Day 0
measure: Measure of patient satisfaction for their treatment at Week 24
timeFrame: Week 24
measure: Measure of patient satisfaction for their treatment at Week 48
timeFrame: Week 48
measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .
timeFrame: Week 24
measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .
timeFrame: Week 48
measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4
timeFrame: Week 4
measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24
timeFrame: Week 24
measure: Measure of the profile of genotypic resistance in plasma in case of virologic failure
timeFrame: Week 24
measure: Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL
timeFrame: Week 24
Other outcomes:
Locations:
city: Point-a-pitre
country: France
facility: CHU Guadeloupe
state: Guadeloupe
city: Fort de France
country: France
facility: CHU de Fort de France
state: Martinique
city: Besançon
country: France
facility: Chu Jean Minjoz
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bondy
country: France
facility: Hôpital Jean Verdier
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Dijon
country: France
facility: CHU de DIJON
city: La Roche sur Yon
country: France
facility: CHD La Roche sur Yon
city: Le Kremlin Bicetre
country: France
facility: CHU Kremlin Bicêtre
city: Levallois-perret
country: France
facility: Hôpital Perpetuel Secours
city: Nantes
country: France
facility: CHU de Nantes
city: Paris Cedex 10
country: France
facility: Hôpital Saint Louis
city: Paris cedex 18
country: France
facility: CHU BICHAT - Claude Bernard
city: Paris
country: France
facility: CHU Hôtel Dieu Paris
city: Paris
country: France
facility: Hôpital La Pitié Salpêtrière
city: Paris
country: France
facility: Hôpital Necker - enfants Malades
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Saint Denis
country: France
facility: CH Delafontaine
city: Saint Etienne
country: France
facility: CHU Saint Etienne
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Suresnes
country: France
facility: Hôpital FOCH
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours Cedex 09
country: France
facility: CHRU de Tours
city: VANDOEUVRE LES NANCY cedex
country: France
facility: CHU de Nancy
Study officials:
References: