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

• 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 ] [ Designated as safety issue: No ]
  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)
• 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 ] [ Designated as safety issue: No ]

• Virologic Response Over Time in Phase I of the Study [ Time Frame: Weeks 4, 8 & 12 ] [ Designated as safety issue: No ]
  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.
• HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study [ Time Frame: Baseline and Weeks 4, 8, 12 & LOCF ] [ Designated as safety issue: No ]
  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
• Virologic Response Over Time in Phase II of the Study [ Time Frame: Weeks II-4, 8, 12 & 16 ] [ Designated as safety issue: No ]
  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.
• CD4+ Lymphocyte Count Change From Baseline [ Time Frame: Phase I Baseline and Phase II Weeks II-1, 12, 16, and LOCF ] [ Designated as safety issue: No ]

  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.

• Percentage of Patients With Ongoing Injection Site Reactions (ISRs) [ Time Frame: Phase I and II ] [ Designated as safety issue: Yes ]

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.

• 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 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).
  Interventions:

  • Drug: enfuvirtide [Fuzeon]
  • Drug: Optimized background ARV
  • Drug: Integrase inhibitor
• 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.

  Interventions:

  • Drug: Optimized background ARV
  • Drug: Integrase inhibitor
  • Drug: enfuvirtide [Fuzeon]

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