Clinical trial NCT00487188: A Study to Evaluate the Safety and Efficacy of Adding Enfuvirtide to Oral Highly Active Antiretroviral Therapy (HAART) in Human Immunodeficiency Virus (HIV) Patients With Prior Treatment Experience
Official title: Phase IIIb/IV Randomized, Controlled Study Evaluating an Intensification Treatment Strategy of Adding Enfuvirtide (ENF) to an Oral Highly Active AntiRetroviral Therapy (HAART) in Treatment Experienced Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-06-15
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the efficacy of enfuvirtide (Fuzeon) added to HAART compared to treatment with HAART alone in achieving and maintaining viral load suppression.

Detailed description: This study consisted of two phases. In the Induction phase patients were randomized at Baseline 1 (BL1) in a 1:2 ratio to receive:

* I1: HAART or
* I2: Enfuvirtide (90 mg twice a day) + HAART.

Participants who achieved viral suppression \< 50 copies/mL by week 24, confirmed by week 28 or earlier, qualified to enter the Maintenance Phase which started at Baseline 2 (BL2), four weeks after confirmation of response. The Maintenance Phase consisted of three treatment groups:

* M1: HAART continued (patients from I1)

Patients on ENF+HAART (I2) were re-randomized (at a 1:1 ratio) at BL2 to:

* M2: Enfuvirtide stopped and HAART continued
* M3: Enfuvirtide + HAART continued.

The duration of the Maintenance Phase was from BL2 up to 48 weeks after BL1. BL2 could start at the earliest at Week 12 and at the latest Week 32.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infected adults \>=18 years of age;
* currently on antiretroviral (ARV) therapy;
* previously treated with 2 or 3 different antiretroviral classes;
* HIV-1 Ribonucleic acid (RNA) \>=1,000 copies/mL;
* Cluster differentiation antigen four (CD4) lymphocyte count \>=200 cells/mm\^3;
* females of childbearing potential must be willing to use a reliable form of effective barrier contraception for the duration of the study and for 30 days after the last dose of study drug.

Exclusion Criteria:

* history of prior use of enfuvirtide or T-1249;
* women who are pregnant, breastfeeding or planning to become pregnant during the study;
* active, untreated opportunistic infection;
* patients on treatment interruption, or patients interrupting ARV therapy within 4 weeks of screening or during the screening period for reasons either than toxicity management.

Primary outcomes:
measure: Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase
timeFrame: From Baseline 1 to Week 28
Secondary outcomes:
measure: Time to Achieving HIV-1 RNA < 50 Copies/mL During the Induction Phase
timeFrame: Baseline 1 until Week 28.
measure: Number of Participants With Viral Suppression HIV-1 RNA < 400 Copies/mL During the Induction Phase
timeFrame: From Baseline 1 to Week 28
measure: Change From Baseline to Week 24 in Viral Load
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Cluster Differentiation Antigen Four Positive (CD4+) Cell Counts
timeFrame: Baseline and Week 24
measure: Percentage of Induction Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks
timeFrame: Week 48
measure: Percentage of Maintenance Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks
timeFrame: Week 48
measure: Change From Baseline to Week 48 in Cluster Differentiation Antigen Four Positive (CD4) Cell Counts
timeFrame: Baseline 1 and Week 48
measure: Time to Loss of Viral Response During the Maintenance Phase
timeFrame: From Baseline 2 to Week 48.
measure: Time to Virological Failure During the Maintenance Phase
timeFrame: From Baseline 2 to Week 48.
measure: Number of Participants With Virological Failure During the Maintenance Phase
timeFrame: From Baseline 2 to Week 48.
measure: Percentage of Participants Maintaining CD4+ Count During the Maintenance Phase
timeFrame: Baseline 2 to Week 48.
measure: Percentage of Participants With Improvement in CD4+ Count During the Maintenance Phase
timeFrame: Baseline 2 to Week 48.
measure: Number of Participants With Adverse Events (AEs) During the Induction Phase
timeFrame: Start of the study treatment until the end of the Induction Phase (Week 12 to Week 32)
Other outcomes:
Locations:
city: Cleveland
country: United States
state: Ohio
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Vancouver
country: Canada
state: British Columbia
city: Le Kremlin-bicetre
country: France
city: Nantes
country: France
city: Paris
country: France
city: Poitiers
country: France
city: Villeneuve-sur-lot
country: France
city: Berlin
country: Germany
city: Bonn
country: Germany
city: Erlangen
country: Germany
city: Frankfurt Am Main
country: Germany
city: Ramat Gan
country: Israel
city: Bagno A Ripoli
country: Italy
city: Bari
country: Italy
city: Brescia
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Roma
country: Italy
city: Roma
country: Italy
city: Mexico City
country: Mexico
city: Amsterdam
country: Netherlands
city: Tilburg
country: Netherlands
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Cádiz
country: Spain
city: Córdoba
country: Spain
city: Huelva
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: San Sebastian
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Zürich
country: Switzerland
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Clotet B, Capetti A, Soto-Ramirez LE, Gatell JM, Rowell L, Salgo M, Schapiro JM. A randomized, controlled study evaluating an induction treatment strategy in which enfuvirtide was added to an oral, highly active antiretroviral therapy regimen in treatment-experienced patients: the INTENSE study. J Antimicrob Chemother. 2008 Dec;62(6):1374-8. doi: 10.1093/jac/dkn377. Epub 2008 Sep 8.