Back to resultsA 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)
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Enfuvirtide
Highly active antiretroviral treatment (HAART)
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ENF + HAART
HAART
Arm Description
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.
Participants received an oral highly active antiretroviral treatment (HAART) regimen, consisting of 3-5 antivirals for up to 48 weeks.
Outcomes
Primary Outcome Measures
Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase
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
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
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
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
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
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
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
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
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 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
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00487188
Brief Title
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
Acronym
INTENSE
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
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
April 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ENF + HAART
Arm Type
Experimental
Arm Description
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.
Arm Title
HAART
Arm Type
Active Comparator
Arm Description
Participants received an oral highly active antiretroviral treatment (HAART) regimen, consisting of 3-5 antivirals for up to 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Enfuvirtide
Other Intervention Name(s)
Fuzeon
Intervention Description
90 mg subcutaneous injection twice a day
Intervention Type
Drug
Intervention Name(s)
Highly active antiretroviral treatment (HAART)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Viral Suppression: HIV-1 RNA < 50 Copies/mL During the Induction Phase
Description
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.
Time Frame
From Baseline 1 to Week 28
Secondary Outcome Measure Information:
Title
Time to Achieving HIV-1 RNA < 50 Copies/mL During the Induction Phase
Description
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.
Time Frame
Baseline 1 until Week 28.
Title
Number of Participants With Viral Suppression HIV-1 RNA < 400 Copies/mL During the Induction Phase
Description
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.
Time Frame
From Baseline 1 to Week 28
Title
Change From Baseline to Week 24 in Viral Load
Description
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.
Time Frame
Baseline and Week 24
Title
Change From Baseline to Week 24 in Cluster Differentiation Antigen Four Positive (CD4+) Cell Counts
Description
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.
Time Frame
Baseline and Week 24
Title
Percentage of Induction Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks
Description
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.
Time Frame
Week 48
Title
Percentage of Maintenance Phase Participants With Viral Load < 50 Copies/mL at 48 Weeks
Description
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.
Time Frame
Week 48
Title
Change From Baseline to Week 48 in Cluster Differentiation Antigen Four Positive (CD4) Cell Counts
Description
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 Frame
Baseline 1 and Week 48
Title
Time to Loss of Viral Response During the Maintenance Phase
Description
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 Frame
From Baseline 2 to Week 48.
Title
Time to Virological Failure During the Maintenance Phase
Description
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.
Time Frame
From Baseline 2 to Week 48.
Title
Number of Participants With Virological Failure During the Maintenance Phase
Description
Virological failure was defined by 2 consecutive HIV-1 RNA values ≥ 400 copies/mL during the Maintenance Phase.
Time Frame
From Baseline 2 to Week 48.
Title
Percentage of Participants Maintaining CD4+ Count During the Maintenance Phase
Description
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.
Time Frame
Baseline 2 to Week 48.
Title
Percentage of Participants With Improvement in CD4+ Count During the Maintenance Phase
Description
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.
Time Frame
Baseline 2 to Week 48.
Title
Number of Participants With Adverse Events (AEs) During the Induction Phase
Description
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 Frame
Start of the study treatment until the end of the Induction Phase (Week 12 to Week 32)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2C7
Country
Canada
City
Le Kremlin-bicetre
ZIP/Postal Code
94275
Country
France
City
Nantes
ZIP/Postal Code
44035
Country
France
City
Paris
ZIP/Postal Code
75018
Country
France
City
Poitiers
ZIP/Postal Code
86021
Country
France
City
Villeneuve-sur-lot
ZIP/Postal Code
47307
Country
France
City
Berlin
ZIP/Postal Code
12157
Country
Germany
City
Bonn
ZIP/Postal Code
53127
Country
Germany
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
City
Frankfurt Am Main
ZIP/Postal Code
60596
Country
Germany
City
Ramat Gan
ZIP/Postal Code
52662
Country
Israel
City
Bagno A Ripoli
ZIP/Postal Code
50011
Country
Italy
City
Bari
ZIP/Postal Code
70100
Country
Italy
City
Brescia
ZIP/Postal Code
25123
Country
Italy
City
Milano
ZIP/Postal Code
20127
Country
Italy
City
Milano
ZIP/Postal Code
20157
Country
Italy
City
Roma
ZIP/Postal Code
00149
Country
Italy
City
Roma
ZIP/Postal Code
00185
Country
Italy
City
Mexico City
ZIP/Postal Code
14000
Country
Mexico
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
City
Tilburg
ZIP/Postal Code
5022 GC
Country
Netherlands
City
Barcelona
ZIP/Postal Code
08026
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Barcelona
ZIP/Postal Code
08370
Country
Spain
City
Barcelona
ZIP/Postal Code
08901
Country
Spain
City
Cádiz
ZIP/Postal Code
11009
Country
Spain
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
City
Huelva
ZIP/Postal Code
21005
Country
Spain
City
Madrid
ZIP/Postal Code
28034
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Malaga
ZIP/Postal Code
29010
Country
Spain
City
San Sebastian
ZIP/Postal Code
20014
Country
Spain
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
City
Valencia
ZIP/Postal Code
46014
Country
Spain
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
18782780
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.
Results Reference
derived
Learn more about this trial
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
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