Clinical Trial Result Information

Title of Study:
A 48-week, randomized, open-label, multicenter, prospective study comparing treatment with double-boosted saquinavir mesylate + lopinavir/ritonavir in combination with ENfuvirtide HAART versus double-boosted saquinavir mesylate + lopinavir/ritonavir + multiple Nucleoside Combination to evaluate Efficacy in HIV-1 positive patients. (ENHANCE study).

Fast Facts:

Protocol number:	ML18021
Sponsor:	Hoffmann-La Roche Ltd; Trimeris Inc.
Company division:	Pharmaceutical
Product name:	Fuzeon
Generic name:	enfuvirtide
Phase of development:	IV
Therapeutic area, approved indication:	HIV Infections
Date of report:	3/1/2006

Clinical study summary:
This trial was prematurely terminated, due to failure to meet enrollment timelines. Clinical trial results, other than key safety statements, have not been posted, due to insufficient data.

Study center(s) :
5 centers in the USA.

Objectives:
Primary: To compare the safety and efficacy of a compact enfuvirtide-containing double-boosted protease inhibitor (PI) regimen to a regimen of double-boosted PIs with nucleoside reverse transcriptase inhibitors (NRTIs) in patients with a past antiretroviral treatment history.

Methodology:
At baseline, eligible patients were randomized to 1 of 2 treatment arms:
Arm 1: Fuzeon + saquinavir mesylate + lopinavir/ritonavir (Kaletra)
Arm 2: Saquinavir mesylate + lopinavir/ritonavir (Kaletra) + any 2 or more NRTIs. Choice of NRTIs in FDA approved dosing was at the investigator’s discretion based on genotypic testing.

Patients returned to the clinic for assessments at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48 or early termination. A follow-up visit was scheduled within 4 weeks after the patient’s final visit for assessment of safety.

Number of patients (planned/analyzed):
Planned: 80. Enrolled: 8

Diagnosis and main criteria for inclusion:
HIV-1 infected adults (≥18 years of age), NRTI, non-nucleoside reverse transcriptase inhibitor (NNRTI) and PI experienced, fusion inhibitor naϊve. Patients had up to 3 baseline NRTI resistance mutations and at least 1 baseline primary PI mutation at the time of study entry. Patients had to be on failing HAART at the time of enrolment, so that the HIV resistance pattern at baseline was likely to reflect the resistance mutations accumulated.

Test product, dose and mode of administration or test procedure:
Fuzeon (enfuvirtide) 90mg sc bid, saquinavir mesylate 1000mg po bid, Kaletra (lopinavir/ritonavir) 400/100mg po bid.

Duration of treatment:
48 weeks

Reference therapy, dose and mode of administration or reference procedure:
Saquinavir mesylate 1000mg po bid, Kaletra (lopinavir/ritonavir) 400/100mg po bid, + any 2 or more NRTIs.

Criteria for evaluation (efficacy, safety):
Efficacy: Main parameters were plasma HIV-1 RNA levels and CD4+ lymphocyte counts.
Safety: Incidence of adverse events (AEs), serious adverse events (SAEs) and treatment-emergent Grade 3 or 4 laboratory abnormalities, including injection site reactions (ISRs). Incidence of AIDS-defining events (Weeks 24 and 48). Deaths. Changes from baseline in clinical laboratory parameters and bone density.

Statistical methods:
All randomized patients were evaluated for safety. Safety data were summarized using descriptive statistics.

Summary (efficacy, safety, other results):
Efficacy: The study was terminated early. Efficacy analyses were not performed. Safety: In total, there were 11 AEs reported among the 4 patients in Arm 1 and 1 AE reported in 1 of the 4 patients in Arm 2. The single AE reported in Arm 2 was candidiasis, which was categorized as moderate in intensity and unrelated to trial medication. The most common AEs in Arm 1 were administration conditions: injection site reaction (3 patients); injection site induration (1 patient), and injection site pruritus (1 patient). All administration site conditions were considered probably related to trial treatment by the investigator. All other AEs in Arm 1 were evaluated as unrelated or possibly related (i.e. neutropenia, weight increase) to trial treatment. There were no deaths on study or within 4 weeks of stopping treatment. No SAEs were reported and no patient was withdrawn from the study due to AEs. There were no unusual or unexpected laboratory abnormalities in this patient population during the treatment period. Vital signs results were unremarkable. Conclusions: The treatment regimens assessed in this study were generally well tolerated in HIV-1 infected, treatment-experienced patients. No other conclusions can be drawn from this study, due to its early termination.

Conclusions:
Efficacy: The study was terminated early. Efficacy analyses were not performed.
Safety: In total, there were 11 AEs reported among the 4 patients in Arm 1 and 1 AE reported in 1 of the 4 patients in Arm 2. The single AE reported in Arm 2 was candidiasis, which was categorized as moderate in intensity and unrelated to trial medication. The most common AEs in Arm 1 were administration conditions: injection site reaction (3 patients); injection site induration (1 patient), and injection site pruritus (1 patient). All administration site conditions were considered probably related to trial treatment by the investigator. All other AEs in Arm 1 were evaluated as unrelated or possibly related (i.e. neutropenia, weight increase) to trial treatment.
There were no deaths on study or within 4 weeks of stopping treatment. No SAEs were reported and no patient was withdrawn from the study due to AEs.
There were no unusual or unexpected laboratory abnormalities in this patient population during the treatment period. Vital signs results were unremarkable.

Publications (references, if available):
The treatment regimens assessed in this study were generally well tolerated in HIV-1 infected, treatment-experienced patients. No other conclusions can be drawn from this study, due to its early termination.