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

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

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.

Study Overview

• Status: Completed
• Conditions: Active Ulcerative Colitis
• Intervention / Treatment: Drug: BG9418 (Interferon beta-1a); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N1
      • Investigator
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 2H4
      • Investigator
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A1R9
      • Investigator
• Czech Republic
  • Hradec Kralove, Czech Republic
    • Investigator
  • Ostrava, Czech Republic
    • Investigator
  • Parbudice, Czech Republic
    • Investigator
  • Praha 4, Czech Republic
    • Investigator
  • Praha 7, Czech Republic
    • Investigator
  • Slany, Czech Republic
    • Investigator
  • Teplice, Czech Republic
    • Investigator
• Hungary
  • Budapest, Hungary
    • Investigator
  • Eger, Hungary
    • Investigator
  • Szeged, Hungary
    • Investigator
  • Szekesfehervar, Hungary
    • Investigator
• Poland
  • Lublin, Poland
    • Investigator
  • Pruszkow, Poland
    • Investigator
  • Sopot, Poland
    • Investigator
  • Torun, Poland
    • Investigator
  • Warszawa, Poland
    • Investigator
  • Wroclaw, Poland
    • Investigator
• Russian Federation
  • Kazan, Russian Federation
    • Investigator
  • Krasnodar, Russian Federation
    • Investigator
  • Lipetsk, Russian Federation
    • Investigator
  • Moscow, Russian Federation
    • Investigator
  • Nizhniy Novgorod, Russian Federation
    • Investigator
  • Rostov-on-Don, Russian Federation
    • Investigator
  • Saratov, Russian Federation
    • Investigator
  • St. Petersburg, Russian Federation
    • Investigator
  • Yaroslavl, Russian Federation
    • Investiator
• Slovakia
  • Nitra, Slovakia
    • Investigator
  • Trencin, Slovakia
    • Investigator
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Investigator
  • Colorado
    • Lakewood, Colorado, United States, 80215
      • Investigator
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Investigator
  • Massachusetts
    • Wellesley Hills, Massachusetts, United States, 02481
      • Investigator
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Investigator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: February 5, 2008
• First Submitted That Met QC Criteria: February 5, 2008
• First Posted (Estimate): February 15, 2008

Study Record Updates

• Last Update Posted (Estimate): August 13, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Interferon-beta
• Other Study ID Numbers: 108UC201; 2007-004867-22 (EudraCT Number)