Clinical Trial to Assess the Efficacy of Darunavir/Ritonavir (DRV/r), Etravirine (ETV) and Raltegravir (MK-0518) in HIV Patients With Resistant Viruses - Full Text View

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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS Potassium

Drug Information available for: Ritonavir Enfuvirtide Darunavir Etravirine Raltegravir Darunavir ethanolate Raltegravir potassium

U.S. FDA Resources

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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)

Intervention Details:

400 mg twice a day

Other Name: Isentress

2 pills of 300 mg twice a day

Other Name: Prezista

2 pills of 100 mg twice a day

Other Name: TMC125

NRTIs and or enfuvirtide (investigator choice)

Other Names:

OBT
enfuvirtide

Detailed Description:

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 (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 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: NCT00460382

Locations


France
Hôpital Gustave Dron, Service Maladies Infectieuses
Tourcoing, France, 59208

Sponsors and Collaborators

French National Agency for Research on AIDS and Viral Hepatitis

Merck Sharp & Dohme Corp.

Janssen-Cilag Tibotec

Investigators


Principal Investigator:	Yazdan YAZDANPANAH, MD PHD	Hôpital Tourcoing FRANCE
Study Director:	Geneviève CHENE, MD PHD	INSERM U897 BORDEAUX FRANCE

More Information


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:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Darunavir Raltegravir Potassium Enfuvirtide Etravirine HIV Protease Inhibitors	Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors HIV Integrase Inhibitors Integrase Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors HIV Fusion Inhibitors Viral Fusion Protein Inhibitors

ClinicalTrials.gov processed this record on September 29, 2016

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)