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

NCT00460382 | Completed Phase 2 DMC

• 2 other identifiers: 2007-000670-23ANRS 139 TRIO
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections

Keywords

HIV infections; HIV integrase inhibitor; etravirine; darunavir; MK 0518; raltegravir; Treatment Experienced; Antiviral drug resistance

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with HIV RNA levels of less than 50 copies/ml in an intent to treat analysis at week 24

  week 24

Secondary Outcomes (11)

• 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

  week 24 and 48

• HIV RNA level evolution between baseline and week 48

  from week 0 to 48

• HIV proviral DNA and 2LTR circle HIV DNA between baseline and week 48

  from week 0 to 48

• Number and type of resistance mutations in case of virologic failure occurrence

  from week 0 to 48

• CD4 lymphocyte count and proportion evolution between baseline and week 48

  from week 0 to 48

Interventions

raltegravir potassium DRUG

400 mg twice a day

Also known as: Isentress

darunavir/ritonavir DRUG

2 pills of 300 mg twice a day

Also known as: Prezista

etravirine DRUG

2 pills of 100 mg twice a day

Also known as: TMC125

Optimized background regimen DRUG

NRTIs and or enfuvirtide (investigator choice)

Also known as: OBT, enfuvirtide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• French National Agency for Research on AIDS and Viral Hepatitis: lead
• Merck Sharp & Dohme LLC: collaborator
• Janssen-Cilag Tibotec: collaborator

Study Sites (1)

Hôpital Gustave Dron, Service Maladies Infectieuses

Tourcoing, 59208, France

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; Darunavir; Ritonavir; etravirine; Enfuvirtide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Thiazoles; Azoles; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; HIV Envelope Protein gp41; Viral Fusion Proteins; Membrane Fusion Proteins; Membrane Proteins; Proteins; HIV Antigens; Antigens, Viral; Viral Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins; Antigens; Biological Factors

Study Officials

• Yazdan YAZDANPANAH, MD PHD

  Hôpital Tourcoing FRANCE

  PRINCIPAL INVESTIGATOR

• Geneviève CHENE, MD PHD

  INSERM U897 BORDEAUX FRANCE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: April 12, 2007
• First Posted: April 13, 2007
• Study Start: May 1, 2007
• Primary Completion: March 1, 2008
• Study Completion: September 1, 2009
• Last Updated: September 17, 2010

Record last verified: 2010-09

Locations

FR (1)