- ICH GCP
- US Clinical Trials Registry
- 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 (INTENSE)
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 Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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British Columbia
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Vancouver, British Columbia, Canada, V6Z 2C7
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Le Kremlin-bicetre, France, 94275
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Nantes, France, 44035
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Paris, France, 75018
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Poitiers, France, 86021
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Villeneuve-sur-lot, France, 47307
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Berlin, Germany, 12157
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Bonn, Germany, 53127
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Erlangen, Germany, 91054
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Frankfurt Am Main, Germany, 60596
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Ramat Gan, Israel, 52662
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Bagno A Ripoli, Italy, 50011
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Bari, Italy, 70100
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Brescia, Italy, 25123
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Milano, Italy, 20157
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Milano, Italy, 20127
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Roma, Italy, 00149
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Roma, Italy, 00185
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Mexico City, Mexico, 14000
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Amsterdam, Netherlands, 1105 AZ
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Tilburg, Netherlands, 5022 GC
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Barcelona, Spain, 08036
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Barcelona, Spain, 08026
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Barcelona, Spain, 08370
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Barcelona, Spain, 08901
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Cádiz, Spain, 11009
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Córdoba, Spain, 14004
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Huelva, Spain, 21005
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Madrid, Spain, 28046
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Madrid, Spain, 28034
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Madrid, Spain, 28041
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Malaga, Spain, 29010
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San Sebastian, Spain, 20014
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Sevilla, Spain, 41013
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Valencia, Spain, 46014
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Zürich, Switzerland, 8091
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Ohio
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Cleveland, Ohio, United States, 44109
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Texas
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Austin, Texas, United States, 78705
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Dallas, Texas, United States, 75246
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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90 mg subcutaneous injection twice a day
Other Names:
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.
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ACTIVE_COMPARATOR: HAART
Participants received an oral highly active antiretroviral treatment (HAART) regimen, consisting of 3-5 antivirals for up to 48 weeks.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase
Time Frame: From Baseline 1 to Week 28
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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.
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From Baseline 1 to Week 28
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Achieving HIV-1 RNA < 50 Copies/mL During the Induction Phase
Time Frame: Baseline 1 until Week 28.
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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. |
Baseline 1 until Week 28.
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Number of Participants With Viral Suppression HIV-1 RNA < 400 Copies/mL During the Induction Phase
Time Frame: From Baseline 1 to Week 28
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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.
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From Baseline 1 to Week 28
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Change From Baseline to Week 24 in Viral Load
Time Frame: Baseline and Week 24
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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.
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Baseline and Week 24
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Change From Baseline to Week 24 in Cluster Differentiation Antigen Four Positive (CD4+) Cell Counts
Time Frame: Baseline and Week 24
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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.
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Baseline and Week 24
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Percentage of Induction Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks
Time Frame: Week 48
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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.
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Week 48
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Percentage of Maintenance Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks
Time Frame: Week 48
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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.
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Week 48
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Change From Baseline to Week 48 in Cluster Differentiation Antigen Four Positive (CD4) Cell Counts
Time Frame: Baseline 1 and Week 48
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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.
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Baseline 1 and Week 48
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Time to Loss of Viral Response During the Maintenance Phase
Time Frame: From Baseline 2 to Week 48.
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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. |
From Baseline 2 to Week 48.
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Time to Virological Failure During the Maintenance Phase
Time Frame: From Baseline 2 to Week 48.
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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. |
From Baseline 2 to Week 48.
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Number of Participants With Virological Failure During the Maintenance Phase
Time Frame: From Baseline 2 to Week 48.
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Virological failure was defined by 2 consecutive HIV-1 RNA values ≥ 400 copies/mL during the Maintenance Phase.
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From Baseline 2 to Week 48.
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Percentage of Participants Maintaining CD4+ Count During the Maintenance Phase
Time Frame: Baseline 2 to Week 48.
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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.
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Baseline 2 to Week 48.
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Percentage of Participants With Improvement in CD4+ Count During the Maintenance Phase
Time Frame: Baseline 2 to Week 48.
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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.
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Baseline 2 to Week 48.
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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)
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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.
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Start of the study treatment until the end of the Induction Phase (Week 12 to Week 32)
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Anti-HIV Agents
- HIV Fusion Inhibitors
- Viral Fusion Protein Inhibitors
- Enfuvirtide
- Anti-Retroviral Agents
Other Study ID Numbers
- MV18406
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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