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)

• ClinicalTrials.gov Identifier: NCT00487188
• Recruitment Status: Completed
• First Posted: June 15, 2007
• Results First Posted: September 2, 2011
• Last Update Posted: August 13, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

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

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: November 2005
• Actual Primary Completion Date: November 2007
• Actual Study Completion Date: April 2008

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase [ Time Frame: 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 :

1. Time to Achieving HIV-1 RNA < 50 Copies/mL During the Induction Phase [ Time Frame: 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.

2. Number of Participants With Viral Suppression HIV-1 RNA < 400 Copies/mL During the Induction Phase [ Time Frame: 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.
3. Change From Baseline to Week 24 in Viral Load [ Time Frame: 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.
4. Change From Baseline to Week 24 in Cluster Differentiation Antigen Four Positive (CD4+) Cell Counts [ Time Frame: 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.
5. Percentage of Induction Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks [ Time Frame: 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.
6. Percentage of Maintenance Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks [ Time Frame: 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.
7. Change From Baseline to Week 48 in Cluster Differentiation Antigen Four Positive (CD4) Cell Counts [ Time Frame: 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.
8. Time to Loss of Viral Response During the Maintenance Phase [ Time Frame: 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.

9. Time to Virological Failure During the Maintenance Phase [ Time Frame: 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.

10. Number of Participants With Virological Failure During the Maintenance Phase [ Time Frame: From Baseline 2 to Week 48. ]
    Virological failure was defined by 2 consecutive HIV-1 RNA values ≥ 400 copies/mL during the Maintenance Phase.
11. Percentage of Participants Maintaining CD4+ Count During the Maintenance Phase [ Time Frame: 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.
12. Percentage of Participants With Improvement in CD4+ Count During the Maintenance Phase [ Time Frame: 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.
13. 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) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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, 20127

Milano, Italy, 20157

Roma, Italy, 00149

Roma, Italy, 00185

Mexico

Mexico City, Mexico, 14000

Netherlands

Amsterdam, Netherlands, 1105 AZ

Tilburg, Netherlands, 5022 GC

Spain

Barcelona, Spain, 08026

Barcelona, Spain, 08036

Barcelona, Spain, 08370

Barcelona, Spain, 08901

Cádiz, Spain, 11009

Córdoba, Spain, 14004

Huelva, Spain, 21005

Madrid, Spain, 28034

Madrid, Spain, 28041

Madrid, Spain, 28046

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00487188
• Other Study ID Numbers: MV18406
• First Posted: June 15, 2007
• Results First Posted: September 2, 2011
• Last Update Posted: August 13, 2015
• Last Verified: July 2015

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Anti-Retroviral Agents; Enfuvirtide; Antiviral Agents; Anti-Infective Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents