Efficacy, and Safety Study of Optimized Background Antiretroviral Regimen (OB) in Combination With Enfuvirtide in the Treatment-Experienced Participants With Human Immunodeficiency Virus-1 (HIV-1) Infection

Open-label, Randomised and Multi-center Study Evaluating the Efficacy and Safety of an Optimised Background Antiretroviral Regimen (OB) Compared to OB Associated With Enfuvirtide in Previously Treated HIV-1 Infected Patients in Virological Success After a 28-week Induction Treatment With Enfuvirtide Plus OB

This is an open-label, randomized and multi-center study to compare the efficacy and safety of continued enfuvirtide (Fuzeon) plus (+) OB therapy versus OB alone in participants with HIV-1 infection. Participants will receive an initial 28 week induction treatment with enfuvirtide + OB. After 28 weeks participants with a plasma viral load less than or equal to (</=) 400 copies/milliliter (mL) at Week 16 and less than (<) 50 copies/mL at Week 24 will be randomized in the ratio 1:1 to receive either enfuvirtide + OB or OB alone for another 24 weeks (up to Week 52).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Enfuvirtide; Drug: Optimized background antiretroviral regimen (OB)

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Aix En Provence, France, 13616
  • Angers, France, 49933
  • Annecy, France, 74011
  • Argenteuil, France, 95107
  • Auch, France, 32008
  • Aulnay Sous Bois, France, 93600
  • Avignon, France, 84902
  • Basse-terre, France, 97100
  • Besancon, France, 25030
  • Bobigny, France, 93009
  • Bordeaux, France, 33076
  • Bordeaux, France, 33000
  • Boulogne, France, 62321
  • Bourg En Bresse, France, 01012
  • Caen, France, 14033
  • Carpentras, France, 84200
  • Cayenne, France, 97300
  • Cayenne, France, 97306
  • Colmar, France, 68024
  • Corbeil-essonnes, France, 91106
  • Creteil, France, 94000
  • Fort-de-france, France, 97261
  • Garches, France, 92380
  • Kourou, France, 97487
  • La Roche Sur Yon, France, 85025
  • Lagny-sur-marne, France, 77405
  • Levallois Perret, France, 92309
  • Lyon, France, 69437
  • Lyon, France, 69317
  • Macon, France, 71000
  • Mantes La Jolie, France, 78200
  • Marseille, France, 13385
  • Marseille, France, 13006
  • Marseille, France, 13274
  • Marseille, France, 13915
  • Matoury, France, 97351
  • Montpellier, France, 34295
  • Nantes, France, 44035
  • Nice, France, 06202
  • Nimes, France, 30029
  • Niort, France, 79021
  • Orleans, France, 45100
  • PAU, France, 64046
  • Paris, France, 75018
  • Paris, France, 75970
  • Paris, France, 75743
  • Paris, France, 75651
  • Paris, France, 75674
  • Paris, France, 75015
  • Paris, France, 75010
  • Paris, France, 75571
  • Perpignan, France, 66046
  • Pessac, France, 33600
  • Pointe À Pitre, France, 97159
  • Pontoise, France, 95303
  • Quimper, France, 29000
  • Rennes, France, 35033
  • Rouen, France, 73031
  • Saint Pierre, France, 97448
  • Saint-denis, France, 93202
  • Saint-denis, France, 97400
  • Saint-dizier, France, 52115
  • Strasbourg, France, 67091
  • Suresnes, France, 92150
  • Toulon, France, 83000
  • Toulouse, France, 31059
  • Toulouse, France, 31052
  • Tours, France, 37044
  • Valenciennes, France, 59322
  • Vandoeuvre-les-nancy, France, 54511
  • Villejuif, France, 94804

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants with HIV-1 infection
• Female participants without any risk of pregnancy
• Participants previously treated with drugs of 2 or 3 different antiretroviral classes
• Participants currently on highly active antiretroviral treatment (HAART) for more than 4 weeks and with a plasma viral load between 1,000 and 300,000 copies of HIV-1 ribonucleic acid per milliliter (RNA/mL)
• Participants with the possibility of potentially effective OB without enfuvirtide, consisting to 2 to 5 drugs, at least two of which are active from at least two different antiretroviral classes
• Cluster of differentiation 4 (CD4) cell count greater than (>) 50 cells/cubic millimeter (mm^3) at screening
• Participants in whom resistance mutations have been detected in reverse transcriptase and/or protease genes
• Enfuvirtide-naive participants

Exclusion Criteria:

• Women of childbearing age not using effective mechanical contraception
• Pregnant or breastfeeding women
• Presence of HIV-2 coinfection
• Participants participating or having participated to another clinical trial during the 30 days prior to selection for this trial
• Participants having previously been treated with enfuvirtide
• Presence active opportunistic infection within 1 month of study entry
• Existence of Grade 4 clinical or laboratory abnormalities
• Cirrhosis or severe hepatic failure
• Uncontrolled diabetes or requiring insulin
• Consumption of alcohol and/or narcotics and/or other substances

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enfuvirtide + OB (Not Randomized); Participants will receive enfuvirtide 90 milligram (mg) twice daily (b.i.d.) and OB as per investigator's discretion for 28 weeks during induction period. After induction period participants not meeting the randomization criteria will receive enfuvirtide 90 mg b.i.d and OB for next 24 weeks (up to Week 52).	Drug: Enfuvirtide; Participants will receive 90 mg enfuvirtide subcutaneously (SC) b.i.d.; Other Names: Fuzeon; Drug: Optimized background antiretroviral regimen (OB); Participants will receive OB (nucleoside and or non-nucleoside reverse transcriptase inhibitor and protease inhibitor) as per investigator's discretion. Protocol does not specify any particular OB drugs.
Experimental: Enfuvirtide + OB (Randomized); Participants will receive enfuvirtide 90 mg b.i.d. and OB as per investigator's discretion for 28 weeks during induction period. After induction period participants meeting the randomization criteria will be randomized to receive enfuvirtide 90 mg b.i.d. and OB for next 24 weeks (up to Week 52).	Drug: Enfuvirtide; Participants will receive 90 mg enfuvirtide subcutaneously (SC) b.i.d.; Other Names: Fuzeon; Drug: Optimized background antiretroviral regimen (OB); Participants will receive OB (nucleoside and or non-nucleoside reverse transcriptase inhibitor and protease inhibitor) as per investigator's discretion. Protocol does not specify any particular OB drugs.
Experimental: OB alone (Randomized); Participants will receive enfuvirtide 90 mg b.i.d. and OB as per investigator's discretion for 28 weeks during induction period. After induction period participants meeting the randomization criteria will be randomized to receive OB alone for next 24 weeks (up to Week 52).	Drug: Enfuvirtide; Participants will receive 90 mg enfuvirtide subcutaneously (SC) b.i.d.; Other Names: Fuzeon; Drug: Optimized background antiretroviral regimen (OB); Participants will receive OB (nucleoside and or non-nucleoside reverse transcriptase inhibitor and protease inhibitor) as per investigator's discretion. Protocol does not specify any particular OB drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of randomized participants without virologic failure and with a viral load < 50 copies/mL at Week 52	Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with virologic response (viral load < 50 copies/mL, 200 copies/mL, and 400 copies/mL)	Weeks 2, 4, 8, 12, 16, 24, 28, 32, 36, 44, and 52
Number of participants who complied with enfuvirtide and OB treatments as measured by pharmacokinetic score	Weeks 2, 4, 8, and 24
Quality of life as assessed by medical outcomes study-HIV (MOS-HIV) questionnaire score	Day 0 (inclusion), Weeks 4, 12, 24, 28, 32, 44, and 52 or premature withdrawal
Change from baseline in viral load	Baseline up to Week 52 or premature withdrawal
Proviral deoxyribonucleic acid (DNA) level	Day 0 (inclusion), Weeks 28, and 52 or premature withdrawal
Time to reappearance of viral load above 50 copies/mL in randomized participants	52 weeks
Changes from baseline in CD4 and CD8 cell counts	Day -35 (screening), Day 0 (inclusion), Weeks 4, 12, 24, 28, 36, 44, and 52 or premature withdrawal
Number of virologic failure participants with reverse transcriptase, protease, and coating resistance mutations for plasma HIV-1 RNA and proviral DNA	Day 0 (inclusion) up to Week 52
Number of participants with cause of virologic failure	Day 0 (inclusion), Weeks 2, 4, 8, 16, 28, 32, 36, 44, and 52 or premature withdrawal
Number of participants who complied with enfuvirtide treatment, as assessed by counting treatment units returned versus supplied	Weeks 4, 8, 12, 16, 24, 28, 32, 36, 44, and 52
Number of participants with adverse events	Day 0 (inclusion), Weeks 2, 4, 8, 12, 16, 24, 28, 32, 36, 44, and 52 or premature withdrawal and follow-up (approximately up to 452 days)
Number of participants with missed treatment doses or injections as assessed by compliance questionnaire	Day 0 (inclusion), Weeks 4, 12, 24, 28, 32, 44, and 52 or premature withdrawal
Number of participants with injection site reaction	Day 0 (inclusion), Weeks 2, 4, 8, 12, 16, 24, 28, 32, 36, 44, and 52 or premature withdrawal and follow-up (approximately up to 452 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: April 5, 2016
• First Submitted That Met QC Criteria: April 5, 2016
• First Posted (Estimate): April 11, 2016

Study Record Updates

• Last Update Posted (Estimate): April 11, 2016
• Last Update Submitted That Met QC Criteria: April 5, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Enfuvirtide; Anti-Retroviral Agents
• Other Study ID Numbers: ML18242