Interim Study Report on C98-844
Study Overview This ongoing study is a multi-center, single-arm, open-label study to determine the, pharmacokinetics, pharmacodynamics, safety and antigenicity of liquid HSA-free Avonex@ administered intramuscularly (IM) to subjectswith relapsing multiple sclerosis
(MS). Subjects received liquid HSA-tiee AvonexQ at 30 pg administered as one IM injection onceper week (QW). The duration of subject participation was to be 24 months, where eachmonth was defined as4 weeks.
Approximately 150 subjects were to be enrolled into the study. Subjects were allowed to self-inject study drug or chooseanother personto administer the injections. For the first 24 weeks of study-drug dosing, all subjects were instructed to take acetaminophen (paracetamol), ibuprofen, or naproxen for the prophylaxis of flu-like symptoms. Subjects were allowed to take aspirin only if the above medications were not tolerated. They were allowed additional dosesof acetaminophen (paracetamol), ibuprofen, naproxen, or aspirin within any 24-hour period as necessaryfor relief of interferon-related flu-like symptoms.
Safety parameters assessedfor this report included adverseevents, physical examinations (including vital signs), assessmentof injection site, pregnancy tests, and clinical (chemistry and hematology) laboratory tests.
The presenceof binding antibodies to human interferon beta-la was determined by enzyme linked immunosorbent assay(ELISA), andthe presenceandtiter of neutralizing antibodies was determined by an antiviral cytopathic effect (CPE) assay(Rudick et al, 1998).
Subjects were assessedat screening, baseline, and Months 3, 6,9, 12, 15, 18,21, and 24. Subjects were consideredto have completed the study if they completed 24 months (96 weeks) of treatment.
The interim clinical study report contained in this submission presentsthe results of an analysis performed on 153 subjects enrolled in this study from data collected through 27 February 2002. At the time of this report 124 subjects were actively participating in the study.
Rationale for Study Design The Applicant statedthat they believed that a multi-center, single arm, open-label study in which all subjects received liquid HSA-free Avonex@ was an appropriate study design becausethe they consider the safety and antigenicity of the currently approved lyophilized product to be well established. Thus, the Applicant thought a control arm of lyophilized Avonex@ or placebo was not necessaryfor this study. Results obtained from C98-844 were to be compared back to historical data regarding adversereactions and rates of development of neutralizing antibodies.