NCT02069834WithdrawnPhase 2
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
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Nantes University Hospital
- Locations
- 25
- Primary Endpoint
- Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Arm 1 (intervention)
Experimental
Dolutegravir 50 mg/d + Rilpivirine 25 mg/d qd orally (intake during a meal)
Intervention: Arm 1 (intervention) (Drug)
Arm 2 (control)
Active Comparator
Continuation of existing HAART at the time of randomization
Intervention: Arm 2 (control) (Drug)
Outcomes
Primary Outcomes
Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)
Time Frame: Week 16
Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks
Time Frame: Week 24
Secondary Outcomes
- Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48(Week 48)
- Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48(Week 48)
- Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL(Week 24)
- Measure of the profile of genotypic resistance in plasma in case of virologic failure(Week 24)
- Percentage of patients who discontinued or changed the strategy of the study(Week 48)
- Measure of the HIV-DNA between day 0 and week 48(W48)
- Measure of CD4 lymphocytes at week 24 compared to day 0(Week 24)
- Measure of CD4 lymphocytes at Week 48 compared to Day 0(Week 48)
- Measure of changes in fat mass distribution at Week 48 compared to Day 0(Week 48)
- Number of patients with adverse events of grade 2 to 4(Week 48)
- Measure of adherence to treatment at Week 24 compared to Day 0(Week 24)
- Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0(Week 24)
- Measure of changes in serum lipid parameters at week 48 to Day 0(Week 48)
- Measure of changes in fat mass distribution at week 24 compared to Day 0(Week 24)
- Measure of adherence to treatment at Week 48 compared to Day 0(Week 48)
- Measure of patient satisfaction for their treatment at Day 0(Day 0)
- Measure of patient satisfaction for their treatment at Week 24(Week 24)
- Measure of patient satisfaction for their treatment at Week 48(Week 48)
- 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 .(Week 24)
- 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 .(Week 48)
- Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4(Week 4)
- Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24(Week 24)
Investigators
Study Sites (25)
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