Safety Study of Interferon Beta 1a to for Acute Stroke
Condition: Cerebrovascular Accident
MeSH terms: Stroke
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will examine the safety of the drug interferon beta 1a in patients with acute
      ischemic stroke to determine the highest dose patients can tolerate without serious side
      effects and to determine the best way to give the medication. Ischemic stroke is caused by a
      blood clot blocking the flow of blood to brain tissue, causing loss or impairment of bodily
      functions governed by the affected part of the brain. Interferon beta 1a is approved for use
      in patients with multiple sclerosis to prevent further brain injury caused by inflammation;
      the drug may also help prevent further brain injury in patients with acute stroke.

      Patients between 18 and 85 years of age who have had a stroke and who can begin taking the
      study drug within 24 hours of onset of stroke symptoms may be eligible for this study.
      Candidates are screened with a medical history, physical examination and neurological
      examinations, blood tests, electrocardiogram, and brain imaging with magnetic resonance
      imaging (MRI) or computed tomography (CT) scans.

      Participants are randomly assigned to receive either interferon beta 1a or placebo (an
      inactive substance). For every five patients enrolled, four receive the study drug and one
      receives placebo. The dose of interferon beta 1a is increased in successive groups of
      patients, so that the first group to enter the study receives 11 micrograms (mcg) of the
      drug, the next receives 22 mcg, then 44 mcg, 66 mcg, and 88 mcg. All patients receive their
      first dose intravenously (through a vein); additional doses are given subcutaneously (under
      the skin).

      During their hospital stay all participants receive standard medical care for stroke, have
      neurological checks every 6 hours, and have continuous heart monitoring. To prevent fever,
      they receive medication, such as Tylenol, before each dose of interferon beta 1a or placebo
      and every 6 hours as needed while taking the study drug. Routine blood tests are done at 3
      and 7 days after the first dose of study drug (or at discharge if the patient leaves the
      hospital before 7 days) and again at 14, 21, and 28 days. Neurological examinations are done
      24 hours after starting the study medication, then every day for 14 days, and again on day
      28.

      After discharge from the hospital, patients are seen by a nurse every day foan 14 days after
      the first medication dose. They are contacted by phone on days 17 and 21. On day 28 they
      return to the hospital as an outpatient for a neurological assessment and blood tests.
    

Detailed description: 
      Objectives: Recombinant human interferon beta-1a (IFN-Beta1a) is an FDA approved treatment
      for patients with relapsing remitting multiple sclerosis, in whom the safety profile is well
      characterized. The actions of IFN-Beta1a to inhibit pro-inflammatory cytokines and prevent
      blood brain barrier disruption suggest a therapeutic potential in ischemic stroke, and recent
      experimental evidence supports that effect. This study will be the first clinical trial
      exposure of patients with acute stroke to IFN-Beta1a. The purpose of this study is to
      investigate the safety of IFN-Beta1a (Rebif(Registered Trademark)) in patients with acute
      ischemic stroke.

      Study Population: Patients age 18-85 years with probable or definite acute ischemic
      cerebrovascular syndrome within 24 hours of onset will be studied.

      Design: This is a randomized double-blind placebo-controlled sequential dose escalation,
      phase 1 trial. Five dose cohorts of 5 patients (4:1 active: placebo) will be studied at 11
      mcg, 22 mcg, 44 mcg, 66 mcg and 88 mcg administered daily for 7 days. The first dose will be
      administered intravenously and subsequent doses will be administered subcutaneously. Patients
      will be pre-medicated to prevent fevers, a common complication of interferon treatment, since
      fever may worsen stroke outcome. Patients will be monitored for adverse events and
      neurological outcomes up to 28 days from onset of treatment. Data will be reviewed in an
      ongoing fashion by a data safety monitoring board (DSMB). Dose escalation will be continuous
      unless drug-related toxicity reaches a predetermined level of one dose-limiting adverse event
      (1 of 4 treated) within a dose cohort, in which case a second cohort of 5 patients (4:1) will
      be treated at that dose. The study will be terminated at a dose level at which 2 of 4 or 3 of
      8 patients on active treatment have a severe dose limiting toxicity or when all planned dose
      cohorts have been completed.

      Outcome Measures: Expected, common toxicities with IFN-Beta1a treatment are flu-like symptoms
      (e.g., fevers, myalgias, headaches, fatigue) and injection site reactions. With long term
      administration liver function abnormalities and leukopenia may occur and these will also be
      monitored. Toxicity will be graded according to the NCI criteria as well as study specific
      criteria defined in section 7a. Dose limiting toxicities will be considered any serious
      adverse event or grade 3 toxicity judged to be probably or definitely related to study
      medication or grade 4 or 5 toxicity judged to be possibly, probably or definitely related to
      study medication or any of the predefined study specific criteria. Serum levels of IFN-Beta1a
      and serum markers of IFN-Beta1a activity will be measured to characterize the
      pharmacokinetics and pharmacodynamics of IFN-Beta 1a in acute stroke patients.
    

Intervention name(s): Interferon beta-1a
Intervention type(s): Drug
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a
Primary purpose: Treatment
Keywords: Ischemic; Brain; Inflammation; Clinical Trial; Stroke