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

This study has been terminated.
(This study was terminated early due to poor enrollment.)
Sponsor:
Collaborator:
Trimeris
Information provided by:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00488059
First received: June 18, 2007
Last updated: July 18, 2011
Last verified: July 2011
Results First Received: November 11, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: enfuvirtide [Fuzeon]
Drug: Optimized background ARV
Drug: Integrase inhibitor

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Phase I (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 II - Arm A 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 II - Arm B 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)

Participant Flow for 3 periods

Period 1:   Phase I: ENF 90mg SC BID
    Phase I     Phase II - Arm A     Phase II - Arm B  
STARTED     29     0     0  
COMPLETED     14     0     0  
NOT COMPLETED     15     0     0  

Period 2:   Phase II Arm A:Phase I Then ENF 90mg BID
    Phase I     Phase II - Arm A     Phase II - Arm B  
STARTED     0     9     0  
COMPLETED     0     7     0  
NOT COMPLETED     0     2     0  

Period 3:   Phase II Arm B:Phase I Then ENF 180mg QD
    Phase I     Phase II - Arm A     Phase II - Arm B  
STARTED     0     0     5  
COMPLETED     0     0     1  
NOT COMPLETED     0     0     4  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Phase 1: ENF 90mg SC BID (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).

Baseline Measures
    Phase 1: ENF 90mg SC BID  
Number of Participants  
[units: participants]
  29  
Age  
[units: years]
Mean ± Standard Deviation
  45.4  ± 10.30  
Gender  
[units: participants]
 
Female     5  
Male     24  



  Outcome Measures
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1.  Primary:   Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL   [ Time Frame: Between Week I-4 and Week I-12 of Phase I of the study ]

Measure Type Primary
Measure Title Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population

Reporting Groups
  Description
Phase I: ENF 90mg SC BID (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).

Measured Values
    Phase I: ENF 90mg SC BID  
Number of Participants Analyzed  
[units: participants]
  29  
Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL  
[units: participants]
 
Week 8     8  
Week 12     5  
Week 16     1  

No statistical analysis provided for Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL



2.  Primary:   Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16   [ Time Frame: Week II-16 ]

Measure Type Primary
Measure Title Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16
Measure Description No text entered.
Time Frame Week II-16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population

Reporting Groups
  Description
Phase II Arm A: Phase I Then ENF 90 mg SC BID

(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 II Arm B: Phase I Then ENF 180mg SC QD

(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.


Measured Values
    Phase II Arm A: Phase I Then ENF 90 mg SC BID     Phase II Arm B: Phase I Then ENF 180mg SC QD  
Number of Participants Analyzed  
[units: participants]
  9     5  
Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16  
[units: participants]
  5     3  

No statistical analysis provided for Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16



3.  Secondary:   Virologic Response Over Time in Phase I of the Study   [ Time Frame: Weeks 4, 8 & 12 ]

Measure Type Secondary
Measure Title Virologic Response Over Time in Phase I of the Study
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population

Reporting Groups
  Description
Phase I: ENF 90mg SC BID (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).

Measured Values
    Phase I: ENF 90mg SC BID  
Number of Participants Analyzed  
[units: participants]
  29  
Virologic Response Over Time in Phase I of the Study  
[units: 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  

No statistical analysis provided for Virologic Response Over Time in Phase I of the Study



4.  Secondary:   HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study   [ Time Frame: Baseline and Weeks 4, 8, 12 & LOCF ]

Measure Type Secondary
Measure Title HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Phase I: ENF 90mg SC BID (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).

Measured Values
    Phase I: ENF 90mg SC BID  
Number of Participants Analyzed  
[units: participants]
  29  
HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study  
[units: log10 copies/mL]
Mean ± Standard Deviation
 
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  

No statistical analysis provided for HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study



5.  Secondary:   Virologic Response Over Time in Phase II of the Study   [ Time Frame: Weeks II-4, 8, 12 & 16 ]

Measure Type Secondary
Measure Title Virologic Response Over Time in Phase II of the Study
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
intent-to-treat population

Reporting Groups
  Description
Phase II Arm A: Phase I Then ENF 90mg SC BID

(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 II Arm B: Phase I Then ENF 180mg SC QD

(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.


Measured Values
    Phase II Arm A: Phase I Then ENF 90mg SC BID     Phase II Arm B: Phase I Then ENF 180mg SC QD  
Number of Participants Analyzed  
[units: participants]
  9     5  
Virologic Response Over Time in Phase II of the Study  
[units: 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  

No statistical analysis provided for Virologic Response Over Time in Phase II of the Study



6.  Secondary:   CD4+ Lymphocyte Count Change From Baseline   [ Time Frame: Phase I Baseline and Phase II Weeks II-1, 12, 16, and LOCF ]

Measure Type Secondary
Measure Title CD4+ Lymphocyte Count Change From Baseline
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Phase II Arm A: Phase I Then ENF 90mg BID

(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 II Arm B: Phase I Then ENF 180mg QD

(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.


Measured Values
    Phase II Arm A: Phase I Then ENF 90mg BID     Phase II Arm B: Phase I Then ENF 180mg QD  
Number of Participants Analyzed  
[units: participants]
  9     5  
CD4+ Lymphocyte Count Change From Baseline  
[units: cells/mm3]
Median ( Full Range )
   
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 )  

No statistical analysis provided for CD4+ Lymphocyte Count Change From Baseline



7.  Secondary:   Percentage of Patients With Ongoing Injection Site Reactions (ISRs)   [ Time Frame: Phase I and II ]

Measure Type Secondary
Measure Title Percentage of Patients With Ongoing Injection Site Reactions (ISRs)
Measure Description No text entered.
Time Frame Phase I and II  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Phase I: ENF 90mg SC BID (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 II - Arm A Phase I then ENF 90 mg SC BID
Phase II - Arm B Phase I then ENF 180 mg SC QD

Measured Values
    Phase I: ENF 90mg SC BID     Phase II - Arm A     Phase II - Arm B  
Number of Participants Analyzed  
[units: participants]
  29     9     5  
Percentage of Patients With Ongoing Injection Site Reactions (ISRs)  
[units: 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  

No statistical analysis provided for Percentage of Patients With Ongoing Injection Site Reactions (ISRs)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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