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

Phase 3

Completed

• Conditions: HIV Infections
• Interventions: Drug: Enfuvirtide; Drug: Optimized background antiretroviral regimen (OB)

• Registration Number: NCT02733419
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2004-12
• Primary Completion: 2008-03
• Study Completion: 2008-03
• Status Verified: 2016-04
• Study First Submitted: 2016-04-05
• Study First Submitted QC: 2016-04-05
• Last Update Submitted: 2016-04-05
• Study First Posted: 2016-04-11
• Last Update Posted: 2016-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enfuvirtide + OB (Not Randomized)	Optimized background antiretroviral regimen (OB)	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).
OB alone (Randomized)	Optimized background antiretroviral regimen (OB)	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).
Enfuvirtide + OB (Randomized)	Optimized background antiretroviral regimen (OB)	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).
Enfuvirtide + OB (Randomized)	Enfuvirtide	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).
Enfuvirtide + OB (Not Randomized)	Enfuvirtide	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).
OB alone (Randomized)	Enfuvirtide	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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)