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

Phase 4

Completed

• Conditions: HIV Infections
• Interventions: Drug: Enfuvirtide; Drug: Highly active antiretroviral treatment (HAART)

• Registration Number: NCT00487188
• Lead Sponsor: Hoffmann-La Roche

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.

Study Timeline

• Study Start: 2005-11
• Study First Submitted: 2007-06-14
• Study First Submitted QC: 2007-06-14
• Study First Posted: 2007-06-15
• Primary Completion: 2007-11
• Study Completion: 2008-04
• Results First Submitted: 2011-03-22
• Results First Submitted QC: 2011-08-02
• Results First Posted: 2011-09-02
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-22
• Last Update Posted: 2015-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ENF + HAART	Highly active antiretroviral treatment (HAART)	Participants received Enfuvirtide (ENF) 90 mg administered by subcutaneous injection twice a day for up to 48 weeks in addition to an oral highly active antiretroviral treatment (HAART) regimen for up to 48 weeks.
HAART	Highly active antiretroviral treatment (HAART)	Participants received an oral highly active antiretroviral treatment (HAART) regimen, consisting of 3-5 antivirals for up to 48 weeks.
ENF + HAART	Enfuvirtide	Participants received Enfuvirtide (ENF) 90 mg administered by subcutaneous injection twice a day for up to 48 weeks in addition to an oral highly active antiretroviral treatment (HAART) regimen for up to 48 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase	From Baseline 1 to Week 28	Participants whose viral load achieved suppression (HIV-1 RNA \< 50 copies/mL) at Week 24 at the latest, confirmed at Week 28 (2 consecutive assessments ≥ 28 days apart) were defined as responders. Patients who discontinued the study or did not respond to assigned treatment by week 28 were considered as non-responders.

Secondary Outcome Measures

Name	Time	Method
Time to Loss of Viral Response During the Maintenance Phase	From Baseline 2 to Week 48.	The time to loss of viral response (defined as HIV-1 RNA \<50 copies/mL) was counted from Baseline 2 until the first of two consecutive ≥50 copies/mL measurements.; Only patients who were qualified for entering the Maintenance Phase were included in the analysis.
Time to Virological Failure During the Maintenance Phase	From Baseline 2 to Week 48.	Time to virological failure (defined as HIV-1 RNA ≥ 400 copies/mL) was counted from Baseline 2 until the first of the two consecutive ≥400 copies/mL measurements.; Only patients who were qualified for entering the Maintenance Phase were included in the analyses.
Number of Participants With Virological Failure During the Maintenance Phase	From Baseline 2 to Week 48.	Virological failure was defined by 2 consecutive HIV-1 RNA values ≥ 400 copies/mL during the Maintenance Phase.
Number of Participants With Adverse Events (AEs) During the Induction Phase	Start of the study treatment until the end of the Induction Phase (Week 12 to Week 32)	A serious AE (SAE) is an event which: results in death, is life-threatening, disabling or incapacitating; is a congenital anomaly in the offspring of a patient who received study drug; requires or prolongs inpatient hospitalization; jeopardizes the patient or require medical or surgical intervention to prevent one of the outcomes above; any Grade 4 laboratory value considered by the investigator clinically significant or that requires an action; any injection site reaction that meets SAE criteria above. Non-serious AEs reported include pneumonia and non-serious AEs that led to discontinuation.
Time to Achieving HIV-1 RNA < 50 Copies/mL During the Induction Phase	Baseline 1 until Week 28.	The time to achieving HIV-1 RNA \<50 copies/mL was counted from Baseline 1 until the first of the two consecutive \<50 copies/mL measurements.; Patients who discontinued from the study or patients who did not have confirmed virological response by week 28 were classed as non-responders and censored at Week 24.
Number of Participants With Viral Suppression HIV-1 RNA < 400 Copies/mL During the Induction Phase	From Baseline 1 to Week 28	Participants whose viral load achieved suppression (HIV-1 RNA \< 400 copies/mL) by Week 24 at the latest, confirmed at Week 28 (2 consecutive assessments ≥ 28 days apart) were defined as responders. Patients who discontinued the study or did not respond to assigned treatment by Week 28 were considered as non-responders.
Change From Baseline to Week 24 in Viral Load	Baseline and Week 24	Change from Baseline in log10 HIV-1 RNA at Week 24. Least squares means were calculated from an analysis of covariance (ANCOVA) model with treatment, a flag variable "removed ENF at re-randomization" and Baseline viral load as independent variables.
Change From Baseline to Week 24 in Cluster Differentiation Antigen Four Positive (CD4+) Cell Counts	Baseline and Week 24	Change from Baseline in CD4+ Cell Counts at Week 24. Least squares means were calculated from an ANCOVA model with treatment as an independent variable.
Percentage of Induction Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks	Week 48	The percentage of participants from the Induction Phase who maintained HIV-1 RNA \< 50 Copies/mL at Week 48. Patients who discontinued from the study, rebounded to ≥ 50 copies/mL (i.e., had two consecutive readings ≥ 50 copies/mL), had missing data or had virological failure by Week 48 were classed as non-responders.
Percentage of Maintenance Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks	Week 48	The percentage of participants from the Maintenance Phase who maintained HIV-1 RNA \< 50 copies/mL at Week 48. Patients who discontinued from the study, rebounded to ≥ 50 copies/mL (i.e., had two consecutive readings ≥ 50 copies/mL), had missing data or had virological failure by Week 48 were classed as non-responders.
Change From Baseline to Week 48 in Cluster Differentiation Antigen Four Positive (CD4) Cell Counts	Baseline 1 and Week 48	Change from Baseline in CD4 Cell Counts at Week 48. Least squares means were calculated from an ANCOVA model with treatment and baseline CD4 count as independent variables.
Percentage of Participants With Improvement in CD4+ Count During the Maintenance Phase	Baseline 2 to Week 48.	Improvement of CD4+ count defined as having from 100 to less than 200 CD4+ cells/mm\^3 at Baseline 2 (BL2) and greater than or equal to 200 cells/mm\^3 at Week 48.
Percentage of Participants Maintaining CD4+ Count During the Maintenance Phase	Baseline 2 to Week 48.	Maintenance of CD4+ count defined as having greater than or equal to 200 cells/mm\^3 at Baseline 2 (BL2) and greater than or equal to 200 cells/mm\^3 at Week 48.