Dolutegravir + Rilpivirine Switch Study (DORISS)

This study has been withdrawn prior to enrollment.
(One of the both Funder partners decided to stop the study before the initiation : thus no product provided and no funding to realize the study)
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT02069834
First received: February 18, 2014
Last updated: August 27, 2015
Last verified: August 2015
  Purpose

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.

Condition Intervention Phase
HIV Infection
HAART-treated
Virologically Controlled
Drug: Arm 1 (intervention)
Drug: Arm 2 (control)
Phase 2
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Measure of the profile of genotypic resistance in plasma in case of virologic failure [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Percentage of patients who discontinued or changed the strategy of the study [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Measure of the HIV-DNA between day 0 and week 48 [ Time Frame: W48 ] [ Designated as safety issue: Yes ]
    Evolution of the HIV-DNA between Day 0 and week 48

  • Measure of CD4 lymphocytes at week 24 compared to day 0 [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0

  • Measure of CD4 lymphocytes at Week 48 compared to Day 0 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0

  • Number of patients with adverse events of grade 2 to 4 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events

  • Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0 [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0

  • Measure of changes in serum lipid parameters at week 48 to Day 0 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0

  • Measure of changes in fat mass distribution at week 24 compared to Day 0 [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    Changes in fat mass distribution at Week 24 compared to Day 0

  • Measure of changes in fat mass distribution at Week 48 compared to Day 0 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Changes in fat mass distribution at Week 48 compared to Day 0

  • Measure of adherence to treatment at Week 24 compared to Day 0 [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire

  • Measure of adherence to treatment at Week 48 compared to Day 0 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire

  • Measure of patient satisfaction for their treatment at Day 0 [ Time Frame: Day 0 ] [ Designated as safety issue: Yes ]
    Assessment of patient satisfaction for their treatment at D0 by questionnaire

  • Measure of patient satisfaction for their treatment at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    Assessment of patient satisfaction for their treatment at Week 24 by questionnaire

  • Measure of patient satisfaction for their treatment at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Assessment of patient satisfaction for their treatment at Week 48 by questionnaire

  • 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 . [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    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 .

  • 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 . [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    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 .

  • Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]
    Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4

  • Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24

  • Measure of the profile of genotypic resistance in plasma in case of virologic failure [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
  • Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: May 2014
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 (intervention)
Dolutegravir 50 mg/d + Rilpivirine 25 mg/d qd orally (intake during a meal)
Drug: Arm 1 (intervention)
Dolutegravir 50 mg/j + Rilpivirine 25 mg/j qd orally (intake during meal)
Active Comparator: Arm 2 (control)
Continuation of existing HAART at the time of randomization
Drug: Arm 2 (control)
Continuation of existing HAART at the time of randomization

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02069834

Locations
France
CHU Guadeloupe
Point-a-pitre, Guadeloupe, France, 97159
CHU de Fort de France
Fort de France, Martinique, France, 87261
Chu Jean Minjoz
Besançon, France, 25030
Hôpital Avicenne
Bobigny, France, 93000
Hôpital Jean Verdier
Bondy, France, 93140
CHU de Bordeaux
Bordeaux, France, 33076
CHU de DIJON
Dijon, France, 21079
CHD La Roche sur Yon
La Roche sur Yon, France, 85925
CHU Kremlin Bicêtre
Le Kremlin Bicetre, France, 94275
Hôpital Perpetuel Secours
Levallois-perret, France, 92300
CHU de Nantes
Nantes, France, 44093
Hôpital Européen Georges Pompidou
Paris, France, 75908
Hôpital Necker - enfants Malades
Paris, France, 75015
CHU Hôtel Dieu Paris
Paris, France, 75004
Hôpital La Pitié Salpêtrière
Paris, France, 75013
Hôpital Saint Louis
Paris Cedex 10, France, 75475
CHU BICHAT - Claude Bernard
Paris cedex 18, France, 75877
CHU de Rennes - Hôpital Pontchaillou
Rennes, France, 35000
CH Delafontaine
Saint Denis, France, 93200
CHU Saint Etienne
Saint Etienne, France, 42055
CHU de Strasbourg
Strasbourg, France, 67091
Hôpital FOCH
Suresnes, France, 92150
CHU Toulouse
Toulouse, France, 31059
CHRU de Tours
Tours Cedex 09, France, 37044
CHU de Nancy
VANDOEUVRE LES NANCY cedex, France, 54511
Sponsors and Collaborators
Nantes University Hospital
  More Information

No publications provided

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02069834     History of Changes
Other Study ID Numbers: RC13_0322, 2013-003344-23
Study First Received: February 18, 2014
Last Updated: August 27, 2015
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Nantes University Hospital:
Dolutegravir
Rilpivirine
PI- and NRTI- sparing ART regimen
switch study

Additional relevant MeSH terms:
Dolutegravir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015