Clinical Trial to Assess the Efficacy of Darunavir/Ritonavir (DRV/r), Etravirine (ETV) and Raltegravir (MK-0518) in HIV Patients With Resistant Viruses (ANRS139 TRIO)
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Purpose
The purpose of this study is to look at the safety and efficacy of a combination of 3 new antiretroviral drugs: darunavir, etravirine and MK-0518 (raltegravir) in patients who have multi-resistant viruses and limited treatment options. An optimized background regimen that may include nucleoside reverse transcriptase inhibitors (NRTIs) and enfuvirtide can be added, if possible, to this combination. Patients will undergo treatment for 48 weeks and virological efficacy will be evaluated at week 24.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections |
Drug: raltegravir potassium Drug: darunavir/ritonavir Drug: etravirine Drug: Optimized background regimen |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Prospective Clinical Trial to Assess Safety and Efficacy of DRV/r(TMC 114/r), ETV(TMC 125) and MK-0518 in Addition to OBT in HIV-1 Infected Patients With Limited to No Treatment Options ANRS 139 TRIO |
- Proportion of patients with HIV RNA levels of less than 50 copies/ml in an intent to treat analysis at week 24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
- Proportions of patients with HIV RNA levels of less than 50 copies/ml at week 48, with HIV RNA levels of less than 400 copies/ml at weeks 24 and 48 [ Time Frame: week 24 and 48 ] [ Designated as safety issue: No ]
- HIV RNA level evolution between baseline and week 48 [ Time Frame: from week 0 to 48 ] [ Designated as safety issue: No ]
- HIV proviral DNA and 2LTR circle HIV DNA between baseline and week 48 [ Time Frame: from week 0 to 48 ] [ Designated as safety issue: No ]
- Number and type of resistance mutations in case of virologic failure occurrence [ Time Frame: from week 0 to 48 ] [ Designated as safety issue: No ]
- CD4 lymphocyte count and proportion evolution between baseline and week 48 [ Time Frame: from week 0 to 48 ] [ Designated as safety issue: No ]
- HIV infection progression [ Time Frame: from week 0 to 48 ] [ Designated as safety issue: No ]
- Frequency of the study regimen modifications and interruption [ Time Frame: from week 0 to 48 ] [ Designated as safety issue: No ]
- Study regimen tolerance [ Time Frame: from week 0 to 48 ] [ Designated as safety issue: Yes ]
- Study regimen adherence [ Time Frame: from week 0 to 48 ] [ Designated as safety issue: No ]
- Association between study drugs' minimum concentrations at week 4 and week 12 and virologic success at week 24 [ Time Frame: from week 4 to 24 ] [ Designated as safety issue: No ]
- Evolution of pharmacokinetics parameters of study drugs in the PK substudy [ Time Frame: betwwen week 1 and 4 ] [ Designated as safety issue: No ]
| Enrollment: | 103 |
| Study Start Date: | May 2007 |
| Study Completion Date: | September 2009 |
| Primary Completion Date: | March 2008 (Final data collection date for primary outcome measure) |
-
Drug: raltegravir potassium
- OBT
- enfuvirtide
Methods: A phase II pilot, prospective, open label, single arm multicentric clinical trial assessing a darunavir/ritonavir, etravirine and MK-0518-containing regimen, if possible associated to an optimized background regimen that may include NRTIs and enfuvirtide, in HIV-1 infected patients failing combination antiretroviral therapy with multi-resistant viruses.
Treatment strategy: Patients will receive raltegravir (MK-0518), darunavir/ritonavir (TMC114/r) and etravirine (TMC125) and if possible an optimized background therapy.
- raltegravir (MK-0518) (400 mg x 2/d = one 400 mg pill twice daily)
- darunavir (600 mg x 2/d= two 300 mg pills twice daily with meal)
- ritonavir (100 mg x 2/d = one 100 mg pill twice daily with meal)
- etravirine (200 mg x 2/d = two 100 mg pills twice daily with meal)
- if possible an optimized background therapy: may include NRTI(s) and enfuvirtide but not nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). NRTIs choice is left to the clinician's discretion. Enfuvirtide is highly recommended in enfuvirtide-naive patients but is left to the clinician.
Main outcome: proportion of patients with HIV RNA levels of less than 50 copies/ml in an intent to treat analysis at W24.
Secondary outcomes: proportions of patients with HIV RNA levels of less than 50 copies/ml at week 48, with HIV RNA levels of less than 400 copies/ml at week 24 and 48; HIV RNA level evolution between baseline and week 48; HIV proviral DNA and 2LTR circle HIV DNA between baseline and week 48; number and type of resistance mutations in case of virologic failure occurrence; CD4 lymphocyte count and proportion evolution between baseline and week 48; HIV infection progression; frequency of the study regimen modifications and interruption; study regimen tolerance; study regimen adherence; association between study drugs' minimum concentrations at week 4 and virologic success at week 24; evolution of pharmacokinetic parameters of study drugs between week 1 and week 4 in the Pharmacokinetic substudy.
Sample size: 103 patients
Enrollment period: 24 weeks
Patient's participation duration: 52 weeks
An extended follow-up (from week 52 to week 96) has been added in April 2008.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age: 18 years and above
- Documented HIV-1 infection.
- History of virological failure on NNRTIs (patients with a history of toxicity to nevirapine and efavirenz may be enrolled in this study).
- On a combination antiretroviral therapy for at least 8 weeks prior to the screening visit (if on tipranavir, or enfuvirtide these drugs should have been introduced more than 8 weeks before the screening visit).
- Patient naive to darunavir, etravirine and to integrase inhibitors
- Plasma viral load at screening visit over 1000 copies/ml, (no CD4 restriction).
-
Genotypic resistance testing at the screening visit:
- Protease inhibitor mutations: over or equal to 3 primary protease inhibitor mutations among: D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54M, L76V, V82A/F/L/T/S, I84V, N88S and L90M (IAS list 2006) but below or equal to 3 mutations among the following: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V et L89V (virus sensitivity to darunavir/ritonavir).
- Reverse transcriptase mutations: over or equal to 3 NRTI mutations (among IAS list) and below or equal to 3 mutations among: A98G, L100I, K101Q/P/E, K103H/N/S/T, V106A/M, V108I, E138G/K/Q, V179D/E/F/G/I, Y181C/I/V/C/H/L, Y188C/H/L, G190A/C/E/Q/S, P225H, F227C/L, M230I/L, P236L, K238N/T and Y318F (virus sensitivity to etravirine)
Exclusion Criteria:
- Non effective barrier contraception in women of child bearing potential
- Pregnant women or women who are breastfeeding
- Opportunistic infection at the acute phase
- Decompensated cirrhosis (stage B or C of Child-Pugh score)
- Malignancy requiring chemotherapy or radiotherapy
- Contraindicated medications being taken by the patient (listed in protocol)
- Allergy to the active substances and expedients of darunavir, etravirine and raltegravir.
- Haemoglobin < 7g/dl, neutrophil cell count < 500/mm3, platelets < 50,000/mm3, creatinine clearance < 50 ml/mn, P. alkaline, AST, ALT or total bilirubin over or equal to 3 times normal values.
- Patients receiving experimental agents with an exclusion period for participation in other studies applicable at the screening visit of the current study.
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00460382
| France | |
| Hôpital Gustave Dron, Service Maladies Infectieuses | |
| Tourcoing, France, 59208 | |
| Principal Investigator: | Yazdan YAZDANPANAH, MD PHD | Hôpital Tourcoing FRANCE | |
| Study Director: | Geneviève CHENE, MD PHD | INSERM U897 BORDEAUX FRANCE |
More Information
No publications provided
| Responsible Party: | French National Agency for Research on AIDS and Viral Hepatitis |
| ClinicalTrials.gov Identifier: | NCT00460382 History of Changes |
| Other Study ID Numbers: | 2007-000670-23, ANRS 139 TRIO |
| Study First Received: | April 12, 2007 |
| Last Updated: | September 16, 2010 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
|
HIV infections HIV integrase inhibitor etravirine darunavir |
MK 0518 raltegravir Treatment Experienced Antiviral drug resistance |
Additional relevant MeSH terms:
|
Darunavir Etravirine Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors |
HIV Protease Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Protease Inhibitors Reverse Transcriptase Inhibitors Therapeutic Uses |
ClinicalTrials.gov processed this record on March 03, 2015