A Phase 2 Study of Interferon Beta-1a (Avonex®) in Ulcerative Colitis

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the clinical activity of interferon beta-1a in participants with moderate to severe ulcerative colitis (UC). Secondary objectives of this study are to determine (i) the safety and tolerability of interferon beta-1a in participants with moderate to severe UC, and (ii) the percentage of participants, with a decrease in the Simple Clinical Colitis Activity Index (SCCAI) score of ≥3 points at Week 8.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Avonex® in Subjects With Moderate to Severe Ulcerative Colitis

Conditions
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Active Ulcerative Colitis

Intervention / Treatment
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* Drug: BG9418 (Interferon beta-1a)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Established diagnosis of ulcerative colitis (UC) for ≥6 months 20 cm active disease at Screening endoscopy Must have active UC with a Mayo Score/Disease Activity Index (DAI) of 6 to 13 points and moderate to severe disease on endoscopy (Mayo endoscopic score of at least 2) despite prior or concomitant treatment Colonoscopy within past 5 years for extent of disease and to exclude polyps For subjects with UC for more than 10 years, colonoscopy with appropriate biopsies within 1 year prior to Screening to exclude dysplasia and neoplasia. Must be willing and able to practice effective birth control during the study and for 1 month after the last dose of study treatment. Key Exclusion Criteria: Diagnosis of indeterminate colitis or Crohn's disease Need for imminent surgery Diagnosis of primary sclerosing cholangitis or toxic megacolon Hemoglobin ≤9 g/dL White blood cell count < 3500 cells/mm^3 Lymphocyte count <1000 cells/µL Platelet count <100,000 cells/µL Female subjects who are pregnant or who wish to become pregnant during the study, or who are lactating Known symptomatic colonic stricture Stool cultures positive for enteric infection History of malignant disease History of major abdominal surgery (e.g., gastrectomy) within past 5 years History of small bowel or colonic obstruction or resection History of drug or alcohol abuse (as defined by the Investigator) within 2 years prior to Screening Use of anti-diarrheal agents during the screening period Previous participation in this study Previous treatment with interferon beta or other interferon products NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interferon beta-1a<br>Interferon beta-1a 30 µg intramuscular (IM) injection twice weekly for 12 weeks | Drug: BG9418 (Interferon beta-1a)<br>* Avonex IM injection, self-administered per protocol<br>* Other names: Avonex®;|
| Placebo Comparator: Placebo<br>Placebo IM injection twice weekly for 12 weeks | Drug: Placebo<br>* Placebo IM injection, self-administered per protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Clinical Response | Clinical response is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, accompanied by a decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore of 1 or less. Baseline was defined as the score collected during the screening period. The Mayo Score/Disease Activity Index (DAI) measures disease activity through assessment of 4 items: stool frequency, rectal bleeding, endoscopy findings, and Physician Global Assessment (PGA). Each item of the score is assessed on a 4-point scale, 0, 1, 2, or 3, with a higher score representing greater severity. In this study, the endoscopy subscore was expanded to a 5-point scale to increase sensitivity in this important dimension of the disease (0=normal/inactive disease, 4=deep ulceration). The Total Mayo Score can therefore range from 0 to13 points. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE, can therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AE's were analyzed based on the principle of treatment emergence. An AE was regarded as treatment-emergent if it was not present prior to receiving the first injection but subsequently appeared, or if it was present prior to receiving the first injection and subsequently worsened in severity. | Up to 16 weeks | 
| Percentage of Participants With a Decrease on Simple Clinical Colitis Activity Index (SCCAI) of ≥3 Points at Week 8 | The SCCAI measures disease activity as defined by both participants and examiners and includes the following 13 items: general well-being, abdominal pain, bowel frequency, stool consistency, bleeding, anorexia, nausea or vomiting, abdominal tenderness, extra-intestinal complications (eye, mouth, joint, skin), temperature, sigmoidoscopic assessment, nocturnal bowel movements, and urgency of defecation. Scores range from 0 to 19 points, and scores <2.5 have been shown to correlate with Patient-Defined Remission, and a decrease of >1.5 points from Baseline correlates with Patient-Defined Significant Improvement. Baseline is defined as the mean of the screening and visit 1 scores. | Baseline and Week 8 |