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

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00303381
• Other study ID #: 22648
• Status: Completed
• Phase: Phase 2
• First received: March 14, 2006
• Last updated: August 4, 2013
• Start date: December 2001
• Est. completion date: January 2003

Study information

• Verified date: August 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: January 2003
• Est. primary completion date: January 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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.
• Placebo
Matching Placebo will be administered subcutaneously, three times a week up to Week 8.
• 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.

Locations

Country	Name	City	State
Germany	Research Site	Munich
Israel	Research Site	Ness Ziona
Netherlands	Research Site	Den Haag
Singapore	Research Site	Singapore
Sweden	Research Site	Solna
Switzerland	Research Site	Zug
United Kingdom	Research Site	Feltham

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono	Merck Serono International SA

Countries where clinical trial is conducted

Germany,  Israel,  Netherlands,  Singapore,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (1)

Pena-Rossi C, Schreiber S, Golubovic G, Mertz-Nielsen A, Panes J, Rachmilewitz D, Shieh MJ, Simanenkov VI, Stanton D, Graffner H. Clinical trial: a multicentre, randomized, double-blind, placebo-controlled, dose-finding, phase II study of subcutaneous int — View Citation

Outcome

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

External Links

•   Full FDA approved prescribing information can be found here