Clinical Trial Result Information
Protocol number
ML16812
Title of Study
Multicenter, open-label, early-access program of Fuzeon (enfuvirtide) (T-20/Ro 29-9800, HIV-1 fusion inhibitor) in combination with free choice antiretroviral regimen to assess serious adverse events, serious AIDS-defining events, and tolerability in patients with advanced HIV infection
Sponsor
Roche Laboratories Inc.
Company division
Pharmaceutical
Product name
Fuzeon
Generic name
enfuvirtide
Therapeutic area
HIV infection
Clinical study summary
This multicenter, open-label, single-arm study was an early-access program for patients with HIV infection who were limited by the currently available agents or who had advanced disease and were most in need of treatment. The safety and tolerability of enfuvirtide (Fuzeon) 90 mg given by subcutaneous (sc) injection twice daily was assessed.
Study center(s)
172 study centers in the United States.
Phase of development
III
Objectives
To assess the safety and tolerability of Fuzeon in patients with advanced HIV disease who were limited by the current commercially available ARV agents or agents available through early-access or compassionate use programs.
Methodology
Routine clinical and laboratory assessments as part of standard patient care were used for assessing entry criteria. After completion of the baseline assessment, patients were given sc Fuzeon 90 mg (deliverable dose) twice daily. If possible, patients were to start a new background AVR regimen simultaneously when starting Fuzeon.
Fuzeon could be provided per protocol until 12 weeks after it was commercially available in the United States. Safety data (ie, serious adverse events [SAEs], serious AIDS-defining events, and discontinuations for any reason) were collected for evaluation. Clinical adverse events (AEs) or laboratory abnormalities that were not serious or did not result in discontinuation of Fuzeon were to be collected only if needed to clarify discontinuations or SAEs. HIV-RNA, CD4 lymphocyte count, and routine clinical and laboratory assessments that are part of patients’ standard of care were to be done at the investigator’s discretion. No efficacy measures were collected during this study.
Number of patients (planned/analyzed)
Planned: approximately 600, with the possibility to include additional patients; 679 enrolled; 636 evaluable for safety.
Diagnosis and main criteria for inclusion
Adults or adolescents (≥16 years of age) with HIV-1 infection and CD4 lymphocyte count ≤100 cells/mm3 and HIV-1 RNA viral load ≥10,000 copies/mL while on highly active antiretroviral therapy (HAART). Patients had to be limited by the current commercially available ARV agents or agents available through early-access or compassionate use programs as per the judgment of the investigator, or they had to have advanced disease and be most in need of therapy (defined as prior documented drug resistance to ARV agents or documented evidence of >6 months prior experience to each of the 3 classes of ARV agents.
Test product, dose and mode of administration or test procedure
Fuzeon 90 mg/sc/bid.
Duration of treatment
Patients could continue on Fuzeon until 12 weeks after it was commercially available in the United States
Reference therapy, dose and mode of administration or reference procedure
Not applicable.
Criteria for evaluation (efficacy, safety)
Safety: Serious adverse events: (1) SAEs or clinical laboratory test abnormalities and Grade 4 injection-site reactions (ISRs); (2) Serious AIDS-defining events and (3) AEs that led to discontinuation of Fuzeon.
Tolerability: (1) Premature withdrawal due to AEs or to injection/reconstitution fatigue; and (2) Patient and coordinator assessments of compliance and ISRs: patient journals throughout Week 1 and at Week 12, and coordinator journals at the end of Weeks 1 and 12.
Statistical methods
Analysis plan: No inferential statistical analyses were planned. For this early-access program, safety (ie, SAEs, serious AIDS-defining events, and discontinuations for any reason), tolerability, and patient and coordinator journal data were summarized using descriptive statistics. No efficacy measures were collected during this study.
Summary (efficacy, safety, other results)
Safety – A total of 486 patients (76.4%) received Fuzeon for ≥24 weeks; 150 patients (23.6%) received Fuzeon for <24 weeks. The mean duration of Fuzeon exposure was 23.7 weeks (range, 1 day to 43 weeks). The relatively short treatment duration for many patients was due to the fact that the drug became commercially available within 5 months of study start.
Thirty-five patients died during the study or within 4 weeks after stopping the study treatment. Most deaths were associated with HIV disease.
There were 222 SAEs reported in 143 patients (22.5%). There were no Grade 4 (pain/discomfort) ISRs during the study. The most common SAEs were pneumonia (2.0% of patients) and implant infection (1.4% of patients). All other SAEs occurred in <1% of the study population. All but 13 SAEs were classified by the investigator as not related to study drug.
Forty-eight patients (7.5%) had treatment-emergent AIDS-defining events. The most common events were cytomegalovirus retinitis (1.3% of patients) and Mycobacterium avium complex (1.1% of patients). All other treatment-emergent AIDS-defining events occurred in <1% of patients.
Fifteen patients (2.4%) were reported to have discontinued Fuzeon due to ≥ 1 AE. The most common AE resulting in withdrawal from the study was ISR (0.6% of patients). A further 13 (2%) withdrew due to injection/reconstitution fatigue. Nevertheless, most patients were able to tolerate Fuzeon during the study.
Patients and coordinators were asked to keep a journal to collect information about compliance and ISRs. Between 35% and 45% of patients responded that they had an ISR during the assessment period. More than 80% of patients at each assessment responded that they either had no pain and discomfort associated with the injection or the intensity was mild. For >90% of patients, the injection either did not interfere or interfered slightly with normal work activities. Coordinators found that approximately half of patients (52.7%) had no difficulty performing the injection and reconstitution of study medication at Week 2. By Week 12, most patients (73.1%) had no difficulty performing the injection and reconstitution of study medication.
Conclusions
Treatment with Fuzeon at a dosage of 90 mg twice daily for a mean of 23.7 weeks, range 1 day to 43 weeks was generally safe and well tolerated in multidrug-experienced patients with advanced HIV disease in this early-access program.
Publications (references, if available)
Goodly J, Dolker M, DeMasi R et al. Optimal adherence to enfuvirtide achieved in US early access program. Proceedings DART 2004 (&th International Congress on Drug Therapy in HIV Infection).
Date of report
6/21/2004
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