A Study of Fuzeon (Enfuvirtide) With an Integrase Inhibitor Plus Optimized Background in Treatment-Experienced HIV-1 Infected Patients

Study Overview
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Brief Summary
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This 2-arm study evaluated the efficacy and safety of Fuzeon with an integrase inhibitor in an expanded access program plus an optimized background antiviral regimen (AVR) in HIV-1 infected patients naive to Fuzeon and an integrase inhibitor. In the first cohort phase of the study (Phase I), eligible patients received Fuzeon 90 mg subcutaneously (SC) twice daily until confirmation of response (min/max = 8/16 weeks). In Phase II, the randomised comparator phase of the study, responders were randomized to receive Fuzeon either 90 mg SC twice a day or 180 mg SC once a day for a further 16 weeks. Non-responders and virological failures were terminated from the study. The anticipated time on study treatment was 3-9 months, and the target sample size was 210 individuals.

Official Title
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A Multicenter, Open-label Study Evaluating the Antiviral Activity and Safety of Enfuvirtide (ENF) Once Daily (QD) or Twice Daily (BID) in Triple-class Experienced HIV-1 Infected Patients Changing Their Therapy to a Standard of Care (SOC) Regimen That Includes Initiating Raltegravir Plus an Optimized Background (OB) Antiviral Regimen

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: enfuvirtide [Fuzeon]
* Drug: Optimized background ARV
* Drug: Integrase inhibitor
* Drug: enfuvirtide [Fuzeon]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >=18 years of age HIV-1 infection Triple class treatment-experienced, Fuzeon- and integrase-inhibitor naive GSS >= 3 ; nucleosides excluded Exclusion Criteria: Adverse clinical or laboratory experience >ACTG Grade 4 Untreated infection, intercurrent illness, drug toxicity or other condition contraindicating an antiretroviral regimen Malignancy requiring chemotherapy or radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I<br>Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs). | Drug: enfuvirtide [Fuzeon]<br>* 90 mg SC twice daily<br>Drug: Optimized background ARV<br>* As prescribed<br>Drug: Integrase inhibitor<br>* As prescribed<br>|
| Experimental: Phase II<br>In the randomized comparator Phase II of the trial- (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL from Phase I were randomized to 1 of 2 treatment arms of (Phase II Arm A: Phase I then ENF 90mg SC BID): ENF 90 mg SC BID + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs or (Phase II Arm B: Phase I then ENF 180mg SC QD): ENF 180 mg SC once daily (QD) + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs. | Drug: Optimized background ARV<br>* As prescribed<br>Drug: Integrase inhibitor<br>* As prescribed<br>Drug: enfuvirtide [Fuzeon]<br>* 180 mg SC once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL | Virologic responders were defined as patients who had an initial HIV-1 RNA assessment <= 50 copies/mL during Phase I at any visit between Week I-4 and Week I-12 and a confirmatory viral load assessment ≤ 50 copies/mL at the next visit (Week I-8 to Week II-16) | Between Week I-4 and Week I-12 of Phase I of the study | 
| Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16 |  | Week II-16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic Response Over Time in Phase I of the Study | The number of intent-to-treat (ITT) participants with HIV-1 RNA <= 50 copies/mL and HIV-1 RNA < 400 copies/mL by study week are summarized below. | Weeks 4, 8 & 12 | 
| HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study | Change from baseline in HIV-1 RNA (log10 copies/mL) at study Weeks I-4, 8, 12 & LOCF for ITT patients in Phase I of the study | Baseline and Weeks 4, 8, 12 & LOCF | 
| Virologic Response Over Time in Phase II of the Study | The number of intent-to-treat (ITT) participants with HIV-1 RNA <= 50 copies/mL and HIV-1 RNA < 400 copies/mL by study week. | Weeks II-4, 8, 12 & 16 | 
| CD4+ Lymphocyte Count Change From Baseline | Change from study Phase I baseline in CD4+ lymphocyte count at Phase II study Weeks II - 1, 12, 16, and LOCF by treatment arm. Change from study Phase II baseline in CD4+ lymphocyte count at Phase II study weeks II - 12 and 16. | Phase I Baseline and Phase II Weeks II-1, 12, 16, and LOCF | 
| Percentage of Patients With Ongoing Injection Site Reactions (ISRs) |  | Phase I and II | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Experienced