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

A Multicenter, Open-label Study Evaluating the Antiviral Activity and Safety of Enfuvirtide (ENF) Once Daily (QD) or Twice Daily (BID) in Triple-class Experienced HIV-1 Infected Patients Changing Their Therapy to a Standard of Care (SOC) Regimen That Includes Initiating Raltegravir Plus an Optimized Background (OB) Antiviral Regimen

This 2-arm study evaluated the efficacy and safety of Fuzeon with an integrase inhibitor in an expanded access program plus an optimized background antiviral regimen (AVR) in HIV-1 infected patients naive to Fuzeon and an integrase inhibitor. In the first cohort phase of the study (Phase I), eligible patients received Fuzeon 90 mg subcutaneously (SC) twice daily until confirmation of response (min/max = 8/16 weeks). In Phase II, the randomised comparator phase of the study, responders were randomized to receive Fuzeon either 90 mg SC twice a day or 180 mg SC once a day for a further 16 weeks. Non-responders and virological failures were terminated from the study. The anticipated time on study treatment was 3-9 months, and the target sample size was 210 individuals.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: enfuvirtide [Fuzeon]; Drug: Optimized background ARV; Drug: Integrase inhibitor; Drug: enfuvirtide [Fuzeon]

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00717-1563
  • Santurce, Puerto Rico, 00909
• United States
  • Alabama
    • Hobson City, Alabama, United States, 36201
  • Arizona
    • Phoenix, Arizona, United States, 85006
  • California
    • Los Angeles, California, United States, 90027
    • Los Angeles, California, United States, 90036
    • Los Angeles, California, United States, 90028
    • Los Angeles, California, United States, 90069
    • Modesto, California, United States, 95350
    • Stanford, California, United States, 94305
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
  • Florida
    • Fort Lauderdale, Florida, United States, 33334
    • Fort Lauderdale, Florida, United States, 33307
    • Fort Myers, Florida, United States, 39912
    • Miami, Florida, United States, 33133
    • Miami Beach, Florida, United States, 33139
    • North Palm Beach, Florida, United States, 33408
    • Orlando, Florida, United States, 32803
    • Plantation, Florida, United States, 33317
    • Port St Lucie, Florida, United States, 34952
    • Safety Harbor, Florida, United States, 36495
    • South Miami, Florida, United States, 33143
    • Tampa, Florida, United States, 33614
  • Georgia
    • Atlanta, Georgia, United States, 30309
    • Atlanta, Georgia, United States, 30318
    • Macon, Georgia, United States, 31201
  • Illinois
    • Chicago, Illinois, United States, 60657
  • Maryland
    • Silver Spring, Maryland, United States, 20910
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-3318
  • Missouri
    • Kansas City, Missouri, United States, 64111
    • St Louis, Missouri, United States, 63139
  • New Jersey
    • Newark, New Jersey, United States, 07102
  • New York
    • Briarcliff Manor, New York, United States, 10510
    • Bronx, New York, United States, 10467-2490
    • New York, New York, United States, 10003
    • Rochester, New York, United States, 14604
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102-7017
    • Philadelphia, Pennsylvania, United States, 19107
    • Reading, Pennsylvania, United States, 19601
  • Texas
    • Dallas, Texas, United States, 75246
    • Fort Worth, Texas, United States, 76104
    • Houston, Texas, United States, 77098
  • Virginia
    • Annandale, Virginia, United States, 22003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients, >=18 years of age
• HIV-1 infection
• Triple class treatment-experienced, Fuzeon- and integrase-inhibitor naive
• GSS >= 3 ; nucleosides excluded

Exclusion Criteria:

• Adverse clinical or laboratory experience >ACTG Grade 4
• Untreated infection, intercurrent illness, drug toxicity or other condition contraindicating an antiretroviral regimen
• Malignancy requiring chemotherapy or radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: enfuvirtide [Fuzeon]; 90 mg SC twice daily; Drug: Optimized background ARV; As prescribed; Drug: Integrase inhibitor; As prescribed; Drug: enfuvirtide [Fuzeon]; 180 mg SC once daily
Experimental: Phase II; In the randomized comparator 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 1 of 2 treatment arms of (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 or (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.	Drug: enfuvirtide [Fuzeon]; 90 mg SC twice daily; Drug: Optimized background ARV; As prescribed; Drug: Integrase inhibitor; As prescribed; Drug: enfuvirtide [Fuzeon]; 180 mg SC once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL	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)	Between Week I-4 and Week I-12 of Phase I of the study
Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16		Week II-16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic Response Over Time in Phase I of the Study	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.	Weeks 4, 8 & 12
HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study	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	Baseline and Weeks 4, 8, 12 & LOCF
Virologic Response Over Time in Phase II of the Study	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.	Weeks II-4, 8, 12 & 16
CD4+ Lymphocyte Count Change From Baseline	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.	Phase I Baseline and Phase II Weeks II-1, 12, 16, and LOCF
Percentage of Patients With Ongoing Injection Site Reactions (ISRs)		Phase I and II

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Trimeris

Publications and helpful links

Helpful Links

• Clinical Study Report Synopsis

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: June 18, 2007
• First Submitted That Met QC Criteria: June 18, 2007
• First Posted (Estimate): June 19, 2007

Study Record Updates

• Last Update Posted (Estimate): July 22, 2011
• Last Update Submitted That Met QC Criteria: July 18, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Treatment Experienced
• 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; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Enfuvirtide; Integrase Inhibitors; HIV Integrase Inhibitors
• Other Study ID Numbers: ML20837