QDISS Stud: QD Isentress as Switch Strategy in Virologically Suppressed HIV-1 Infected-Patient

Sponsor

Nantes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03195452

Collaborator

(none)

100

Enrollment

Locations

Arm

29.9

Actual Duration (Months)

5.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Raltegravir (RAL) is a very effective antiretroviral drug with a favorable long term tolerability. RAL offers many advantages such as lack of drug-drug interactions, a good safety profile particularly on lipids, inflammation and bone parameters. Ral can be an very interesting for patient with comorbidities and comedications, intolerance or toxicities with their current ARV treatment. However its current formulation of one tablet of 400mg twice a day coul not suit many patients.

A new once-a-day formulation of RAL has been developed, with two tablets of 600 mg QD. Pharmacokinetic study in healthy volunteers has shown that this dosing provides increased RAL exposure compared to the standard formulation of 400 mg given twice a day.

The objective of this study is to evaluate the maintain of virologic suppression with raltegravir 600mg 2 tablets qd as part of a triple antiretroviral regimen in virologically controlled patients.

Condition or Disease	Intervention/Treatment	Phase
Virus-HIV	Drug: Raltegravir and 2 Nucleoside/Nucleotide reverse transcriptase inhibitor (NRTI)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Masking Description:

Open label

Primary Purpose:

Treatment

Official Title:

QD Isentress as Switch Strategy in Virologically Suppressed HIV-1 Infected-Patient

Actual Study Start Date :

Nov 8, 2017

Actual Primary Completion Date :

Oct 30, 2019

Actual Study Completion Date :

May 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Raltegravir antiretroviral tritherapy: Raltegravir 600 mg tablet orally (2 tablets QD) and 2 Nucleoside/Nucleotide reverse transcriptase inhibitor (NRTI)	Drug: Raltegravir and 2 Nucleoside/Nucleotide reverse transcriptase inhibitor (NRTI) All virologically suppressed

Arm

Intervention/Treatment

Experimental: Raltegravir

antiretroviral tritherapy: Raltegravir 600 mg tablet orally (2 tablets QD) and 2 Nucleoside/Nucleotide reverse transcriptase inhibitor (NRTI)

Drug: Raltegravir and 2 Nucleoside/Nucleotide reverse transcriptase inhibitor (NRTI)

All virologically suppressed

Outcome Measures

Primary Outcome Measures

Number of copie/ml plasma HIV - RNA [48 weeks]

Secondary Outcome Measures

Score evaluation of patient satisfaction [48 weeks]
Score evaluation of patient quality of life with PROQOL-HIV questionnaires [48 weeks]
Score evaluation of adherence [48 weeks]
Number of incidence of Treatment-Emergent Adverse Events [48 weeks]
Number of patient who have a viral load < 50 copies/ml [48 weeks]
number of discontinuation of Raltegravir [48 weeks]
number of treatment failure [48 weeks]
number of genotype resistance mutations [48 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults of both gender ≥ 18 years
Signed informed consent form
Documented HIV-1 infection
Stable antiretroviral therapy for ≥ 6 months consisting of 2 NRTIs (TDF/FTC or ABC/3TC )+ a 3rd agent either as a once or twice daily regimen, unless there is intolerance requiring change of therapy. In this situation of intolerance, patient with less than 6 months of current antiretroviral therapy will be allowed in the study.

As soon as TAF/FTC will be available in France, patients receiving TAF/FTC + 3rd agent could be enrolled.

Switch of TDF/FTC to TAF/FTC will be authorized as long as the change has occurred for more than 3 months prior to the screening visit. Such switch will be also allowed during the study, and, unless urgently needed, after the W24 visit.

Patients on stable raltegravir 400 mg 1 tablet twice daily plus 2 NRTI can be enrolled; number of these patients will be limited to 33% of the total cohort.

Indication to current change antiretroviral therapy for at least one of the following reasons :

Intolerance or prevention of toxicity
Presence of a comorbid condition justifying change of the 3rd agent
Management of drug-drug-interaction
Patient's request, including switch to simplify or to improve convenience

No prior virological failure on integrase-containing antiretroviral therapy or NNRTI-containing antiretroviral therapy or NRTI only-therapy
HIV-1 RNA < 50 c/mL for ≥ 6 months. However, a single HIV-1 RNA ≥ 50 copies/mL and < 200 copies/mL with a subsequent HIV-1 RNA < 50 c/mL in the past 6 months is allowed.
AST and ALT < 5 times the upper limit of normal
Estimated glomerular filtration rate by MDRD equation >= 50 mL/min
Hemoglobin > 8 g/dL
Platelet count > 50 0000/mm3
For women of childbearing potential: negative serum test for pregnancy and acceptance to use contraceptive methods
Affiliation to a French Social Security program.

Exclusion Criteria:

HIV-2 co-infection
Concomitant treatments contra-indicated with raltegravir
Patients receiving raltegravir 400mg, 2 tablets in one daily intake
Patients with prior virological failure on NRTI+PI/r based regimen can be enrolled as long as historical plasma genotype and/or screening DNA genotype demonstrate absence of resistance or possible resistance to any drug. Subjects with previous failure to any other antiretroviral regimen cannot be enrolled.
Presence of possible resistance or resistance to any nucleoside reverse transcriptase inhibitor or integrase inhibitor on a historical plasma genotype.
Presence of possible resistance or resistance to any non- nucleoside reverse transcriptase inhibitor on a historical plasma genotype, with the exception of polymorphic mutations E138A/G/K/Q/R/S and V179D in patients naïve to NNRTI.
Presence of resistance to any PI on a historical plasma genotype

In case were historical plasma genotype being not available or incomplete, resistance genotype will be performed on DNA at screening visit. Full treatment and cumulative resistance genotype history will have to be provided, at screening, to the principal investigator to approve any inclusion.

For HCV co-infected patients, if specific treatment for hepatitis is required during the trial duration, such HCV therapy should be compatible with the ARV combination and only started after the W24 visit.
HBV infection, in the absence of treatment with TDF or TAF
Severe associated diseases requiring specific treatment, such as curative treatment of acute opportunistic infection
Treatment with interferon, interleukin or any immunotherapeutic agent or chemotherapy
Cancer diagnosis in the past 3 years with the exception of Kaposi sarcoma
Subjects participating in another clinical trial evaluating therapies and having an exclusion period that is still ongoing during the screening phase
Any condition which might compromise the safety of treatment and/or patient's adherence to trial procedures
Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision
Difficulty in terms of follow-up (vacation, job transfer, geographical distance, lack of motivation)

Contacts and Locations

Locations

	Site	City	Country
1	CHU De Bordeaux	Bordeaux	France
2	CH de la Roche Sur Yon	la Roche Sur Yon	France
3	CH du Mans	Le Mans	France
4	CHU de Lyon	Lyon	France
5	CHRU de Montpellier	Montpellier	France
6	CHU of NANTES	Nantes	France
7	CHU de Nice	Nice	France
8	CHR orléans	Orléans	France
9	CHU de Bichat	Paris	France
10	CHu hotel dieu	Paris	France
11	CHU la pitié	Paris	France
12	Hopital Avicenne	Paris	France
13	Hopital Necker	Paris	France
14	Hopital St Louis	Paris	France
15	CHU de Reims	Reims	France
16	CH de Tourcoing	Tourcoing	France
17	CHRU de Tours	Tours	France