Dolutegravir + Rilpivirine Switch Study (DORISS)

HIV Infection Clinical Trial

— 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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02069834
• Other study ID #: RC13_0322
• Secondary ID: 2013-003344-23
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• First received: February 18, 2014
• Last updated: August 27, 2015
• Start date: May 2014
• Est. completion date: October 2017

Study information

• Verified date: August 2015
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HAART-treated
• HIV Infection
• Virologically Controlled

Intervention

Drug:
• Arm 1 (intervention)
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

Locations

Country	Name	City	State
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	CHU de Fort de France	Fort de France	Martinique
France	CHD La Roche sur Yon	La Roche sur Yon
France	CHU Kremlin Bicêtre	Le Kremlin Bicetre
France	Hôpital Perpetuel Secours	Levallois-perret
France	CHU de Nantes	Nantes
France	CHU Hôtel Dieu Paris	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital La Pitié Salpêtrière	Paris
France	Hôpital Necker - enfants Malades	Paris
France	Hôpital Saint Louis	Paris Cedex 10
France	CHU BICHAT - Claude Bernard	Paris cedex 18
France	CHU Guadeloupe	Point-a-pitre	Guadeloupe
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 Cedex 09
France	CHU de Nancy	VANDOEUVRE LES NANCY cedex

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pilot phase: Percentage of patients with plasma viral load = 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)		Week 16	Yes
Primary	Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained = 50 copies/mL throughout 24 weeks		Week 24	Yes
Secondary	Percentage of patients with plasma viral load =50 HIV RNA copies/mL at Week 24 and Week 48		Week 48	Yes
Secondary	Percentage of patients with plasma viral load =50 HIV RNA copies/mL from Day 0 to Week 48		Week 48	Yes
Secondary	Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL		Week 48	Yes
Secondary	Measure of the profile of genotypic resistance in plasma in case of virologic failure		Week 48	Yes
Secondary	Percentage of patients who discontinued or changed the strategy of the study		Week 48	Yes
Secondary	Measure of the HIV-DNA between day 0 and week 48	Evolution of the HIV-DNA between Day 0 and week 48	W48	Yes
Secondary	Measure of CD4 lymphocytes at week 24 compared to day 0	Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0	Week 24	Yes
Secondary	Measure of CD4 lymphocytes at Week 48 compared to Day 0	Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0	Week 48	Yes
Secondary	Number of patients with adverse events of grade 2 to 4	Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events	Week 48	Yes
Secondary	Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0	Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0	Week 24	Yes
Secondary	Measure of changes in serum lipid parameters at week 48 to Day 0	Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0	Week 48	Yes
Secondary	Measure of changes in fat mass distribution at week 24 compared to Day 0	Changes in fat mass distribution at Week 24 compared to Day 0	Week 24	Yes
Secondary	Measure of changes in fat mass distribution at Week 48 compared to Day 0	Changes in fat mass distribution at Week 48 compared to Day 0	Week 48	Yes
Secondary	Measure of adherence to treatment at Week 24 compared to Day 0	Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire	Week 24	Yes
Secondary	Measure of adherence to treatment at Week 48 compared to Day 0	Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire	Week 48	Yes
Secondary	Measure of patient satisfaction for their treatment at Day 0	Assessment of patient satisfaction for their treatment at D0 by questionnaire	Day 0	Yes
Secondary	Measure of patient satisfaction for their treatment at Week 24	Assessment of patient satisfaction for their treatment at Week 24 by questionnaire	Week 24	Yes
Secondary	Measure of patient satisfaction for their treatment at Week 48	Assessment of patient satisfaction for their treatment at Week 48 by questionnaire	Week 48	Yes
Secondary	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 .	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	Yes
Secondary	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 .	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	Yes
Secondary	Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4	Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4	Week 4	Yes
Secondary	Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24	Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24	Week 24	Yes
Secondary	Measure of the profile of genotypic resistance in plasma in case of virologic failure		Week 24	Yes
Secondary	Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL		Week 24	Yes