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

Sponsor:	Hoffmann-La Roche
Collaborator:	Trimeris
Information provided by:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00488059

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: enfuvirtide [Fuzeon] Drug: Optimized background ARV Drug: Integrase inhibitor	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Enfuvirtide

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Enrollment:	29
Study Start Date:	June 2007
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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
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: Optimized background ARV As prescribed Drug: Integrase inhibitor As prescribed Drug: enfuvirtide [Fuzeon] 180 mg SC once daily

Arms

Assigned Interventions

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

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: Optimized background ARV

As prescribed

Drug: Integrase inhibitor

As prescribed

Drug: enfuvirtide [Fuzeon]

180 mg SC once daily

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00488059

Show 43 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Trimeris

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

Additional Information:

Clinical Study Report Synopsis This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Clinical Trials, Study Director, Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00488059 History of Changes
Other Study ID Numbers:	ML20837
Study First Received:	June 18, 2007
Results First Received:	November 11, 2009
Last Updated:	July 18, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Hoffmann-La Roche:

Treatment Experienced

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

Enfuvirtide
Integrase Inhibitors
HIV Fusion Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012