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 (INTENSE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00487188
First received: June 14, 2007
Last updated: May 14, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
HIV Infections
Drug: Enfuvirtide
Drug: Highly active antiretroviral treatment (HAART)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase [ Time Frame: From Baseline 1 to Week 28 ] [ Designated as safety issue: No ]
    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:
  • Time to Achieving HIV-1 RNA < 50 Copies/mL During the Induction Phase [ Time Frame: Baseline 1 until Week 28. ] [ Designated as safety issue: No ]

    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 [ Time Frame: From Baseline 1 to Week 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline 1 and Week 48 ] [ Designated as safety issue: No ]
    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.

  • Time to Loss of Viral Response During the Maintenance Phase [ Time Frame: From Baseline 2 to Week 48. ] [ Designated as safety issue: No ]

    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 [ Time Frame: From Baseline 2 to Week 48. ] [ Designated as safety issue: No ]

    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 [ Time Frame: From Baseline 2 to Week 48. ] [ Designated as safety issue: No ]
    Virological failure was defined by 2 consecutive HIV-1 RNA values ≥ 400 copies/mL during the Maintenance Phase.

  • Percentage of Participants Maintaining CD4+ Count During the Maintenance Phase [ Time Frame: Baseline 2 to Week 48. ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Improvement in CD4+ Count During the Maintenance Phase [ Time Frame: Baseline 2 to Week 48. ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events (AEs) During the Induction Phase [ Time Frame: Start of the study treatment until the end of the Induction Phase (Week 12 to Week 32) ] [ Designated as safety issue: No ]
    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.


Enrollment: 47
Study Start Date: November 2005
Study Completion Date: April 2008
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ENF + 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.
Drug: Enfuvirtide
90 mg subcutaneous injection twice a day
Other Name: Fuzeon
Drug: Highly active antiretroviral treatment (HAART)
An oral HAART regimen of 3-5 antiretrovirals was chosen by the physician and patient, based on the patient's prior treatment history and genotypic antiretroviral resistance testing.
Active Comparator: HAART
Participants received an oral highly active antiretroviral treatment (HAART) regimen, consisting of 3-5 antivirals for up to 48 weeks.
Drug: Highly active antiretroviral treatment (HAART)
An oral HAART regimen of 3-5 antiretrovirals was chosen by the physician and patient, based on the patient's prior treatment history and genotypic antiretroviral resistance testing.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00487188

  Hide Study Locations
Locations
United States, Ohio
Cleveland, Ohio, United States, 44109
United States, Texas
Austin, Texas, United States, 78705
Dallas, Texas, United States, 75246
Canada, British Columbia
Vancouver, British Columbia, Canada, V6Z 2C7
France
Le Kremlin-bicetre, France, 94275
Nantes, France, 44035
Paris, France, 75018
Poitiers, France, 86021
Villeneuve-sur-lot, France, 47307
Germany
Berlin, Germany, 12157
Bonn, Germany, 53127
Erlangen, Germany, 91054
Frankfurt Am Main, Germany, 60596
Israel
Ramat Gan, Israel, 52662
Italy
Bagno A Ripoli, Italy, 50011
Bari, Italy, 70100
Brescia, Italy, 25123
Milano, Italy, 20157
Milano, Italy, 20127
Roma, Italy, 00185
Roma, Italy, 00149
Mexico
Mexico City, Mexico, 14000
Netherlands
Amsterdam, Netherlands, 1105 AZ
Tilburg, Netherlands, 5022 GC
Spain
Barcelona, Spain, 08370
Barcelona, Spain, 08901
Barcelona, Spain, 08036
Barcelona, Spain, 08026
Cádiz, Spain, 11009
Córdoba, Spain, 14004
Huelva, Spain, 21005
Madrid, Spain, 28046
Madrid, Spain, 28041
Madrid, Spain, 28034
Malaga, Spain, 29010
San Sebastian, Spain, 20014
Sevilla, Spain, 41013
Valencia, Spain, 46014
Switzerland
Zürich, Switzerland, 8091
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00487188     History of Changes
Other Study ID Numbers: MV18406
Study First Received: June 14, 2007
Results First Received: March 22, 2011
Last Updated: May 14, 2012
Health Authority: Spain: Agency of Medicines

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Enfuvirtide
HIV Fusion Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014