Safety and Efficacy of Interferon-Beta-1a (Rebif®) for Treating Subjects With Acute Symptoms of Ulcerative Colitis

This study has been completed.
Sponsor:
Collaborator:
Merck Serono International SA
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00303381
First received: March 14, 2006
Last updated: August 4, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to determine the safety and efficacy of interferon-beta-1a in subjects with active ulcerative colitis (UC).


Condition Intervention Phase
Ulcerative Colitis
Drug: Interferon-beta-1a, 44 microgram
Drug: Placebo
Drug: Interferon-beta-1a, 66 microgram
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Multicentre, Randomised, Double-blind, Placebo-controlled, Dose-finding Phase II Study of Subcutaneously Administered IFN-beta-1a in the Treatment of Patients With Moderately Active Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Percentage of subjects with endoscopically confirmed remission [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of subjects with clinical remission [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]
  • Percentage of subjects with clinical remission at Week 8 and 12 [ Time Frame: Week 8 and 12 ] [ Designated as safety issue: No ]
  • Time to first occurrence of clinical remission [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]
  • Time to first occurrence of endoscopically confirmed remission [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]
  • Percentage of subjects with clinical remission two weeks after endoscopically confirmed remission [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]
  • Percentage of subjects with clinical response [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]
  • Time to first occurrence of clinical response [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]
  • Change from Baseline in Ulcerative Colitis Scoring System (UCSS) total score and sub-scores at Week 2, 4, 6, 8 and 12 [ Time Frame: Baseline, Week 2, 4, 6, 8 and 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score and sub-scores at Week 4, 8 and 12 [ Time Frame: Baseline, Week 4, 8 and 12 ] [ Designated as safety issue: No ]
  • Percentage of subjects with an increase in IBDQ score of at least 15 points [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]
  • Change from Baseline in C-reactive protein level at Week 2, 4, 8 and 12 [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
  • Changes from Baseline in erythrocyte sedimentation rate at Week 2, 4, 8 and 12 [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
  • Percentage of subjects with treatment failure [ Time Frame: Baseline up to Week 12 or early withdrawal or treatment failure ] [ Designated as safety issue: No ]

Enrollment: 194
Study Start Date: December 2001
Study Completion Date: January 2003
Primary Completion Date: January 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Interferon-beta-1a, 44 microgram Drug: Interferon-beta-1a, 44 microgram
Interferon-beta-1a will be administered subcutaneously at a dose of 44 mcg, three times a week up to Week 8.
Other Name: Rebif®
Experimental: Interferon-beta-1a, 66 microgram Drug: Interferon-beta-1a, 66 microgram
Interferon-beta-1a will be administered subcutaneously at a dose of 66 mcg, three times a week up to Week 8.
Other Name: Rebif®
Placebo Comparator: Placebo Drug: Placebo
Matching Placebo will be administered subcutaneously, three times a week up to Week 8.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Moderately active UC, defined as:

    • Diagnosis of UC documented by clinical, radiological and endoscopic or histological findings
    • Proctosigmoidoscopic diagnosis: at least left-sided disease; the extent of the colonic inflammation is to be more than 20 centimeter from the anal verge
    • A flare in disease activity considered moderate in according to the UCSS during the 14 days before initiation of study medication. Moderate disease is defined as a UCSS between 6 and 10 with a UCSS Physician's Global Assessment less than (<) 3 and a proctosigmoidoscopy score of 2 or 3
  • At least one previous flare-up of UC
  • Maintenance treatment with 5-aminosalicylic acid (5-ASA) at a stable dose for the management of UC is allowed, but not required. The daily dose of 5-ASA has to be stable for at least 4 weeks before Study Day 1 and has to be no more than 3.6 gram/day. This dose has to be maintained throughout the study. Corticosteroids will not be allowed during the study, with the exceptions of inhaled steroids and topical dermatological steroids
  • Age ≥18 years, of either sex
  • Adequate bone marrow reserve: white blood cells (WBC) greater than (>) 3.5*10^9 per liter (/L), neutrophils >1.5*10 ^9 /L, thrombocytes >100 *10^9 /L, hemoglobin >8.5 gram per deciliter (g/dL)
  • Female subjects are to be neither pregnant nor breast-feeding and has to lack childbearing potential, as will be defined by either being post-menopausal or surgically sterile or using a hormonal contraceptive, intra-uterine device, diaphragm with spermicide or not pregnant which will be established by a negative serum or urinary Human chorionic gonadotrophin (hCG) test within 7 days before Study Day 1. A pregnancy test is not required if the subject was post-menopausal or surgically sterile
  • Willingness and ability to comply with the protocol for the duration of the study
  • Written informed consent, obtained before any study-related procedure not part of the subject's normal medical care, with the understanding that the subject can withdraw consent at any time without prejudice to his or her future medical care

Exclusion Criteria:

  • Previous systemic treatment with interferons, immunosuppressive therapy (for example [e.g.], cyclosporin, azathioprine, 6-mercaptopurine) or other biological treatment (e.g. anti- Cluster of differentiation [CD] 4, anti-CD5, anti- Tumour necrosis factor [TNF]-alpha, Interleukin [IL]-10) in the 3 months before Study Day 1
  • Any other investigational drug or any experimental procedure in the 4 weeks before Study Day 1
  • More than three doses of rectally administered 5-ASA derivatives in the 2 weeks before Study Day 1
  • More than two doses of systemically or rectally administered corticosteroids in the 14 days before Study Day 1
  • Use of non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotic therapy (e.g. metronidazole) in the 2 weeks before Study Day 1
  • Use of codeine, other narcotics, loperamide or opiates after the Screening visit or during the study
  • Stool examination positive for enteric pathogens, pathogenic ova, parasites, or Clostridium toxin at Screening
  • Need for emergency surgery (uncontrollable hemorrhage, persistent non-inflammatory intestinal obstruction - at the Investigator's discretion - or perforation), elective surgery during the study, or surgery in the 4 weeks before study entry
  • Inadequate liver function, defined by a total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase level >2 times the upper limit of the normal range
  • Inadequate renal function, defined by serum creatinine >2.0 milligram per deciliter (mg/dL)
  • Histopathological findings of high-grade dysplasia or history of cancer (except carcinoma in situ of the cervix or adequately treated basal cell or squamous cell carcinoma of the skin)
  • Known allergies to paracetamol or to any of the ingredients of the medicinal product (that is, the active substance, human serum albumin or mannitol)
  • Severe depressive disorder or suicidal ideation, or epilepsy with a history of seizures not adequately controlled by treatment
  • Known alcohol or drug abuse within the past 5 years
  • Other serious concurrent systemic disorders incompatible with the study (at the Investigator's discretion)
  • Severe active infection (at the Investigator's discretion)
  • Dependence on a liquid diet
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303381

Locations
Germany
Research Site
Munich, Germany
Israel
Research Site
Ness Ziona, Israel
Netherlands
Research Site
Den Haag, Netherlands
Singapore
Research Site
Singapore, Singapore
Sweden
Research Site
Solna, Sweden
Switzerland
Research Site
Zug, Switzerland
United Kingdom
Research Site
Feltham, United Kingdom
Sponsors and Collaborators
EMD Serono
Merck Serono International SA
Investigators
Study Director: Claudia Pena Rossi, M.D. Merck Serono International SA
  More Information

Additional Information:
Publications:
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00303381     History of Changes
Other Study ID Numbers: 22648
Study First Received: March 14, 2006
Last Updated: August 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes
Interferon beta 1a
Interferon-beta
Interferons
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on August 20, 2014