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A Study of Fuzeon (Enfuvirtide) With an Integrase Inhibitor Plus Optimized Background in Treatment-Experienced HIV-1 Infected Patients (AMICI)

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ClinicalTrials.gov Identifier: NCT00488059
Recruitment Status : Terminated (This study was terminated early due to poor enrollment.)
First Posted : June 19, 2007
Results First Posted : June 29, 2011
Last Update Posted : July 22, 2011
Sponsor:
Collaborator:
Trimeris
Information provided by:
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: enfuvirtide [Fuzeon]
Drug: Optimized background ARV
Drug: Integrase inhibitor
Enrollment 29
Recruitment Details  
Pre-assignment Details Phase I of the study was a single group. In Phase II of the study, the remaining patients were randomized to either the enfuvirtide (90 mg) BID group or the enfuvirtide (180 mg) QD group.
Arm/Group Title Phase I Phase II - Arm A Phase II - Arm B
Hide Arm/Group Description (Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs). Phase I then enfuvirtide 90 mg SC BID + RAL 400 mg PO BID + OB (with at least 1 fully active ARV agent excluding NRTIs) Phase I then enfuvirtide 180 mg SC QD (2 x 90-mg injections) + RAL 400 mg PO BID + OB (with at least 1 fully active ARV agent excluding NRTIs)
Period Title: Phase I: ENF 90mg SC BID
Started 29 0 0
Completed 14 0 0
Not Completed 15 0 0
Period Title: Phase II Arm A:Phase I Then ENF 90mg BID
Started 0 9 0
Completed 0 7 0
Not Completed 0 2 0
Period Title: Phase II Arm B:Phase I Then ENF 180mg QD
Started 0 0 5
Completed 0 0 1
Not Completed 0 0 4
Arm/Group Title Phase 1: ENF 90mg SC BID
Hide Arm/Group Description (Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).
Overall Number of Baseline Participants 29
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants
45.4  (10.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
Female
5
  17.2%
Male
24
  82.8%
1.Primary Outcome
Title Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL
Hide Description Virologic responders were defined as patients who had an initial HIV-1 RNA assessment <= 50 copies/mL during Phase I at any visit between Week I-4 and Week I-12 and a confirmatory viral load assessment ≤ 50 copies/mL at the next visit (Week I-8 to Week II-16)
Time Frame Between Week I-4 and Week I-12 of Phase I of the study
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Phase I: ENF 90mg SC BID
Hide Arm/Group Description:
(Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).
Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: participants
Week 8 8
Week 12 5
Week 16 1
2.Primary Outcome
Title Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16
Hide Description [Not Specified]
Time Frame Week II-16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Phase II Arm A: Phase I Then ENF 90 mg SC BID Phase II Arm B: Phase I Then ENF 180mg SC QD
Hide Arm/Group Description:

(Phase 1: ENF 90 mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

In the randomized comparator phase Phase II of the trial– (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL)from Phase I were randomized to

(Phase II Arm A: Phase I+ENF 90mg SC BID): ENF 90 mg SC BID + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs.

(Phase 1: ENF 90 mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

In the randomized comparator phase Phase II of the trial– (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL)from Phase I were randomized to

(Phase II Arm B: Phase I then ENF 180mg SC QD): ENF 180 mg SC once daily (QD) + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs.

Overall Number of Participants Analyzed 9 5
Measure Type: Number
Unit of Measure: participants
5 3
3.Secondary Outcome
Title Virologic Response Over Time in Phase I of the Study
Hide Description The number of intent-to-treat (ITT) participants with HIV-1 RNA <= 50 copies/mL and HIV-1 RNA < 400 copies/mL by study week are summarized below.
Time Frame Weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Phase I: ENF 90mg SC BID
Hide Arm/Group Description:
(Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).
Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: participants
Week 4 (<= 50 copies/mL) 11
Week 4 (< 400 copies/mL) 22
Week 8 (<= 50 copies/mL) 14
Week 8 (< 400 copies/mL) 22
Week 12 (<= 50 copies/mL) 14
Week 12 (< 400 copies/mL) 19
4.Secondary Outcome
Title HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study
Hide Description Change from baseline in HIV-1 RNA (log10 copies/mL) at study Weeks I-4, 8, 12 & LOCF for ITT patients in Phase I of the study
Time Frame Baseline and Weeks 4, 8, 12 & LOCF
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population. Last Observation Carried Forward (LOCF) includes non-missing data values from the last post-baseline visit for each participant which was carried forward to impute missing data values.
Arm/Group Title Phase I: ENF 90mg SC BID
Hide Arm/Group Description:
(Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).
Overall Number of Participants Analyzed 29
Mean (Standard Deviation)
Unit of Measure: log10 copies/mL
Baseline (N=29) 4.4  (0.87)
change at Week 4 (n=27) 2.1  (0.46)
change at Week 8 (n=24) 2.0  (0.81)
change at Week 12 (n=14) 2.4  (1.09)
change at Week 16 (n=10) 2.3  (0.90)
change at LOCF (n=27) 1.9  (0.61)
5.Secondary Outcome
Title Virologic Response Over Time in Phase II of the Study
Hide Description The number of intent-to-treat (ITT) participants with HIV-1 RNA <= 50 copies/mL and HIV-1 RNA < 400 copies/mL by study week.
Time Frame Weeks II-4, 8, 12 & 16
Hide Outcome Measure Data
Hide Analysis Population Description
intent-to-treat population
Arm/Group Title Phase II Arm A: Phase I Then ENF 90mg SC BID Phase II Arm B: Phase I Then ENF 180mg SC QD
Hide Arm/Group Description:

(Phase 1: ENF 90 mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

In the randomized comparator phase Phase II of the trial– (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL)from Phase I were randomized to

(Phase II Arm A: Phase I then ENF 90mg SC BID): ENF 90 mg SC BID + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs.

(Phase 1: ENF 90 mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

In the randomized comparator phase Phase II of the trial– (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL)from Phase I were randomized to

(Phase II Arm B: Phase I then ENF 180mg SC QD): ENF 180 mg SC once daily (QD) + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs.

Overall Number of Participants Analyzed 9 5
Measure Type: Number
Unit of Measure: participants
Week 4 (<= 50 copies/mL) 5 4
Week 4 (< 400 copies/mL) 6 4
Week 8 (<= 50 copies/mL) 6 4
Week 8 (< 400 copies/mL) 7 4
Week 12 (<= 50 copies/mL) 6 4
Week 12 (< 400 copies/mL) 7 4
Week 16 (<= 50 copies/mL) 5 3
Week 16 (< 400 copies/mL) 6 4
6.Secondary Outcome
Title CD4+ Lymphocyte Count Change From Baseline
Hide Description

Change from study Phase I baseline in CD4+ lymphocyte count at Phase II study Weeks II - 1, 12, 16, and LOCF by treatment arm.

Change from study Phase II baseline in CD4+ lymphocyte count at Phase II study weeks II – 12 and 16.

Time Frame Phase I Baseline and Phase II Weeks II-1, 12, 16, and LOCF
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat
Arm/Group Title Phase II Arm A: Phase I Then ENF 90mg BID Phase II Arm B: Phase I Then ENF 180mg QD
Hide Arm/Group Description:

(Phase 1: ENF 90 mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

In the randomized comparator phase Phase II of the trial– (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL)from Phase I were randomized to

(Phase II Arm A: Phase I then ENF 90mg SC BID): ENF 90 mg SC BID + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs.

(Phase 1: ENF 90 mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

In the randomized comparator phase Phase II of the trial– (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL)from Phase I were randomized to

(Phase II Arm B: Phase I then ENF 180mg SC QD): ENF 180 mg SC once daily (QD) + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs.

Overall Number of Participants Analyzed 9 5
Median (Full Range)
Unit of Measure: cells/mm3
Phase I baseline to Week 1 of Phase II (n=8,5)
22
(-39.0 to 139.0)
118.0
(26.0 to 239.0)
Phase I baseline to Week 12 of Phase II (n=7,4)
83.0
(3.0 to 199.0)
174.5
(-14.0 to 301.0)
Phase I baseline to Week 16 of Phase II (n=6,4)
61.0
(0.0 to 104.0)
179.0
(18.0 to 225.0)
7.Secondary Outcome
Title Percentage of Patients With Ongoing Injection Site Reactions (ISRs)
Hide Description [Not Specified]
Time Frame Phase I and II
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I: ENF 90mg SC BID Phase II - Arm A Phase II - Arm B
Hide Arm/Group Description:
(Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).
Phase I then ENF 90 mg SC BID
Phase I then ENF 180 mg SC QD
Overall Number of Participants Analyzed 29 9 5
Measure Type: Number
Unit of Measure: Percentage of patients
Any type 92 100 100
Pain/discomfort 52 42.9 60
Erythema 80 71.4 100
Induration 80 100 100
Pruritus 44 28.6 20
Nodules 56 57.1 80
Ecchymosis 40 14.3 20
Time Frame Phase I Day 1 through Week 12 & Phase II Day 1 through Week 16
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I: ENF 90mg SC BID Phase II Arm A: Phase I Then ENF 90mg SC BID Phase II Arm B: Phase I Then ENF 180mg SC QD
Hide Arm/Group Description (Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

(Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

In the randomized comparator phase Phase II of the trial– (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL)from Phase I were randomized to

(Phase II Arm A: Phase I then ENF 90mg SC BID): ENF 90 mg SC BID + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs.

(Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® [raltegravir] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs).

In the randomized comparator phase Phase II of the trial– (Day II-1 through Week II-16): Virologic responders confirmed HIV-1 RNA ≤50 copies/mL)from Phase I were randomized

(Phase II Arm B: Phase I then ENF 180mg SC once daily (QD)): ENF 180 mg SC QD + RAL 400 mg PO BID + OB with at least 1 fully active ARV agent excluding NRTIs.

All-Cause Mortality
Phase I: ENF 90mg SC BID Phase II Arm A: Phase I Then ENF 90mg SC BID Phase II Arm B: Phase I Then ENF 180mg SC QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Phase I: ENF 90mg SC BID Phase II Arm A: Phase I Then ENF 90mg SC BID Phase II Arm B: Phase I Then ENF 180mg SC QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/29 (13.79%)   0/9 (0.00%)   0/5 (0.00%) 
Blood and lymphatic system disorders       
Anemia * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
General disorders       
Death * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
Infections and infestations       
Cytomegalovirus viraemia * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
Nervous system disorders       
Cerebrovascular accident * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
Transient ischaemic attack * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
Psychiatric disorders       
Suicidal ideation * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
Renal and urinary disorders       
Renal failure * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary mass * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase I: ENF 90mg SC BID Phase II Arm A: Phase I Then ENF 90mg SC BID Phase II Arm B: Phase I Then ENF 180mg SC QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/29 (6.90%)   0/9 (0.00%)   0/5 (0.00%) 
Gastrointestinal disorders       
Diarrhoea * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash morbilliform * 1  1/29 (3.45%)  0/9 (0.00%)  0/5 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Layout table for additonal information
Responsible Party: Clinical Trials, Study Director, Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00488059     History of Changes
Other Study ID Numbers: ML20837
First Submitted: June 18, 2007
First Posted: June 19, 2007
Results First Submitted: November 11, 2009
Results First Posted: June 29, 2011
Last Update Posted: July 22, 2011