NCT02212379

Brief Summary

This multicenter, international, non randomized (single arm), open, phase II trial aims to evaluate the capacity of the dual combination raltegravir/etravirine to maintain virological success in virologically suppressed HIV-1 infected patients, of at least 45 years of age, switching from a boosted PI-containing regimen. Patients will be followed for 96 weeks. The primary endpoint was the proportion of participants with virological success at 48 weeks. Virological success is defined as the absence of 2 consecutive plasma viral load \>50 copies/mL within 2 to 4 weeks apart. The study was designed to show an efficacy \>90%, assuming a success rate \>95%, with a power of 80% and a 5%type-1 error. A total of 160 individuals was required to achieve the objective. The principal secondary endpoint is the proportion of patients in therapeutic success up to week 48 and 96.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
170

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2015

Typical duration for phase_2

Geographic Reach
2 countries

19 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 30, 2014

Completed
9 days until next milestone

First Posted

Study publicly available on registry

August 8, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

January 1, 2015

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2017

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2018

Completed
2.9 years until next milestone

Results Posted

Study results publicly available

February 5, 2021

Completed
Last Updated

April 27, 2021

Status Verified

March 1, 2021

Enrollment Period

2.8 years

First QC Date

July 30, 2014

Results QC Date

April 20, 2020

Last Update Submit

March 31, 2021

Conditions

HIV-1 Infection

Keywords

RaltegravirEtravirineaged, 45 and overViral loadEfficacySafety

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96

    Virological success is defined as the absence of 2 consecutive plasma viral loads (VL) \> 50 copies/mL within 2 to 4 weeks of a dual raltegravir/etravirine regimen. The proportion of patients who maintained viral suppression under raltegravir plus etravirine was 99.4% (95% confidence interval (95% CI:95.6 -99.9) at week 48 and 98.7% (95% CI: 95.0 -99.7) at week 96

    at week48 and at week 96

Secondary Outcomes (23)

  • Percentage of Patients With Therapeutic Success at Week 48 and Week 96

    weeks 48 and 96

  • Percentage of Patients With Trial Treatment Interruption at Week 48 and Week 96

    weeks 48 and 96

  • Percentage of Patients With With Grade Virological Failure (HIV-RNA Plasma VL Between 51 and 200 Copies/mL)

    weeks 48 and 96

  • Median Time of Virological Failure

    week 96

  • Percentage of Patients With High Grade of Virological Failure Defined as HIV RNA > 200 Copies/mL

    weeks 48 and 96

  • +18 more secondary outcomes

Study Arms (1)

raltegravir and etravirine

EXPERIMENTAL
Drug: raltegravir and etravirine

Interventions

raltegravir and etravirineDRUG

Raltegravir (RAL, ISENTRESS®) 400 mg tablets will be administered as one 400 mg oral tablet PO twice daily (800 mg per day) after a meal. Etravirine (ETR, INTELENCE®) 200 mg tablets will be administered as one 200 mg oral tablet PO twice daily (400 mg per day) after a meal.

raltegravir and etravirine

Eligibility Criteria

Age45 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Documented HIV-1 infection
  • Age ≥ 45 years
  • Naïve to integrase inhibitor and etravirine
  • At least 6 months of stable antiretroviral therapy (ART) including a boosted protease inhibitor, whatever the number of combined drugs
  • HIV-RNA plasma VL ≤ 50 copies/mL during the last 24 months prior to screening visit (Week-6/Week-4), documented by at least 4 time-points with no more than one blip in HIV-RNA plasma viral load between 51 and 200 copies/mL
  • HIV-RNA plasma VL ≤ 50 copies/mL at screening visit (Week-6/Week-4)
  • A genotype is available (on amplified DNA at Week-6/Week-4 Visit and/or on RNA in the medical history of the patient) and shows a virus sensitive to ETR OR no genotype is available (amplification failure on DNA at Week-6/Week-4 Visit and no genotype in the medical history of the patient), there are no virological failure on NNRTI in the medical history
  • CD4+ lymphocytes \> 200 cells/mm3
  • Creatinine \< 2.5 x ULN
  • CPK (Creatine Phospho Kinase) \< 6 ULN (Upper Limit of Normal)
  • AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase) \< 5 ULN
  • Hemoglobin \> 10 g/dL
  • Platelets \> 100 000/mm3
  • Negative urinary pregnancy test and use of efficient contraception for women of childbearing potential
  • For French participants only: subject enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme), article L1121-11 of the Public health code
  • +2 more criteria

You may not qualify if:

  • Previous exposure to raltegravir or etravirine
  • Presence of any documented integrase inhibitor mutation on DNA genotype at Week-6/Week-4 and/or on RNA in the medical history of the patient
  • Positive hepatitis B HBsAg or Positive HBc Ac and negative HBs Ac
  • HIV-2 infection
  • Active viral hepatitis C requiring a specific treatment during the 24 months of the trial
  • Patient with a history of non-compliance or irregular follow-up
  • Initiation of a concomitant anti-hypercholesterolemia (e.g. statins) or antidiabetic treatment within the last 3 months prior the screening visit (Week-6 /Week-4)
  • Patient using: Clopidogrel (Plavix®), Prasugrel (Effient®), Ticagrelor (Brilinta®), Ticlopidine (Ticlid®), Flurbiprofen (Antadys® - Cebutid®), Rifampin (Rifampicin® - Rifadin® - RofactMC - Rifater®), Rifapentine (Priftin®), St John's wort, Carbamazepine (Tegretol®), Phenobarbital, Phenytoin (Dilantin®),Avanafil (Stendra™), Triazolam (Halcion®)
  • Concomitant treatment using interferon, interleukins or any other immunotherapy or chemotherapy
  • Concomitant prophylactic or curative treatment for an opportunistic infection
  • All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with trial protocol compliance, adherence and/or trial treatment tolerance
  • Subjects under judicial protection due to temporarily and slightly diminished mental or physical faculties, or under legal guardianship
  • Pregnant women or breastfeeding women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Hôpital Avicenne

Bobigny, 93000, France

Location

Hôpital Jean Verdier

Bondy, 93140, France

Location

Hôpital Saint André

Bordeaux, 33076, France

Location

Hôpital Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Hôpital Croix Rousse

Lyon, 69317, France

Location

Hôpital Sainte marguerite

Marseille, 13009, France

Location

Hôpital Gui de Chauliac

Montpellier, 34000, France

Location

CHU Hôtel Dieu

Nantes, 44093, France

Location

Hôpital de l'Archet

Nice, 06202, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hôpital Pitié-Salpétrière

Paris, 75013, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hôpital Necker

Paris, 75015, France

Location

Hôpital Bichat Claude Bernard

Paris, 75018, France

Location

Hôpital Européen Georges Pompidou

Paris, 75908, France

Location

Hôpital Bretonneau

Tours, 37044, France

Location

Hospital de Bellvitge

Barcelona, 08000, Spain

Location

Hospital de la santa Creu i San Pau

Barcelona, 08025, Spain

Location

Hospital Clinic

Barcelona, 08036, Spain

Location

Related Links

MeSH Terms

Interventions

Raltegravir Potassiumetravirine

Intervention Hierarchy (Ancestors)

PyrrolidinonesPyrrolidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Limitations and Caveats

The absence of a comparator arm, which in terms of impact on fat, bone density and inflammation/activation markers may limit the interpretation of the observed changes over time. One limitation is the small number of women.

Results Point of Contact

Title
Dr Lambert Assoumou
Organization
Inserm, Sorbonne Universite, IPLESP
lambert.assoumou@iplesp.upmc.fr
0142164280

Study Officials

  • Christine Katlama, MD

    Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

    PRINCIPAL INVESTIGATOR

  • Jacques Reynes, MD

    Département des Maladies Infectieuses et Tropicales Hôpital Gui de Chauliac, CHU de Montpellier France

    STUDY CHAIR

  • Dominique Costagliola, PhD

    Inserm UMR S 1136 Université Pierre et Marie Curie Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Paris, France

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 30, 2014

First Posted

August 8, 2014

Study Start

January 1, 2015

Primary Completion

October 1, 2017

Study Completion

April 1, 2018

Last Updated

April 27, 2021

Results First Posted

February 5, 2021

Record last verified: 2021-03

Locations

ES(3)FR(16)