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

Primary Purpose

Ulcerative Colitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Interferon-beta-1a, 44 microgram
Placebo
Interferon-beta-1a, 66 microgram
Sponsored by
EMD Serono
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Interferon-beta-1a, 44 microgram

Interferon-beta-1a, 66 microgram

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Percentage of subjects with endoscopically confirmed remission

Secondary Outcome Measures

Percentage of subjects with clinical remission
Percentage of subjects with clinical remission at Week 8 and 12
Time to first occurrence of clinical remission
Time to first occurrence of endoscopically confirmed remission
Percentage of subjects with clinical remission two weeks after endoscopically confirmed remission
Percentage of subjects with clinical response
Time to first occurrence of clinical response
Change from Baseline in Ulcerative Colitis Scoring System (UCSS) total score and sub-scores at Week 2, 4, 6, 8 and 12
Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score and sub-scores at Week 4, 8 and 12
Percentage of subjects with an increase in IBDQ score of at least 15 points
Change from Baseline in C-reactive protein level at Week 2, 4, 8 and 12
Changes from Baseline in erythrocyte sedimentation rate at Week 2, 4, 8 and 12
Percentage of subjects with treatment failure

Full Information

First Posted
March 14, 2006
Last Updated
August 4, 2013
Sponsor
EMD Serono
Collaborators
Merck Serono International SA
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1. Study Identification

Unique Protocol Identification Number
NCT00303381
Brief Title
Safety and Efficacy of Interferon-Beta-1a (Rebif®) for Treating Subjects With Acute Symptoms of Ulcerative Colitis
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
December 2001 (undefined)
Primary Completion Date
January 2003 (Actual)
Study Completion Date
January 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono
Collaborators
Merck Serono International SA

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
194 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Interferon-beta-1a, 44 microgram
Arm Type
Experimental
Arm Title
Interferon-beta-1a, 66 microgram
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Interferon-beta-1a, 44 microgram
Other Intervention Name(s)
Rebif®
Intervention Description
Interferon-beta-1a will be administered subcutaneously at a dose of 44 mcg, three times a week up to Week 8.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching Placebo will be administered subcutaneously, three times a week up to Week 8.
Intervention Type
Drug
Intervention Name(s)
Interferon-beta-1a, 66 microgram
Other Intervention Name(s)
Rebif®
Intervention Description
Interferon-beta-1a will be administered subcutaneously at a dose of 66 mcg, three times a week up to Week 8.
Primary Outcome Measure Information:
Title
Percentage of subjects with endoscopically confirmed remission
Time Frame
Baseline up to Week 12 or early withdrawal or treatment failure
Secondary Outcome Measure Information:
Title
Percentage of subjects with clinical remission
Time Frame
Baseline up to Week 12 or early withdrawal or treatment failure
Title
Percentage of subjects with clinical remission at Week 8 and 12
Time Frame
Week 8 and 12
Title
Time to first occurrence of clinical remission
Time Frame
Baseline up to Week 12 or early withdrawal or treatment failure
Title
Time to first occurrence of endoscopically confirmed remission
Time Frame
Baseline up to Week 12 or early withdrawal or treatment failure
Title
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
Title
Percentage of subjects with clinical response
Time Frame
Baseline up to Week 12 or early withdrawal or treatment failure
Title
Time to first occurrence of clinical response
Time Frame
Baseline up to Week 12 or early withdrawal or treatment failure
Title
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
Title
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
Title
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
Title
Change from Baseline in C-reactive protein level at Week 2, 4, 8 and 12
Time Frame
Baseline, Week 2, 4, 8 and 12
Title
Changes from Baseline in erythrocyte sedimentation rate at Week 2, 4, 8 and 12
Time Frame
Baseline, Week 2, 4, 8 and 12
Title
Percentage of subjects with treatment failure
Time Frame
Baseline up to Week 12 or early withdrawal or treatment failure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Pena Rossi, M.D.
Organizational Affiliation
Merck Serono International SA
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Munich
Country
Germany
Facility Name
Research Site
City
Ness Ziona
Country
Israel
Facility Name
Research Site
City
Den Haag
Country
Netherlands
Facility Name
Research Site
City
Singapore
Country
Singapore
Facility Name
Research Site
City
Solna
Country
Sweden
Facility Name
Research Site
City
Zug
Country
Switzerland
Facility Name
Research Site
City
Feltham
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
19145731
Citation
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 interferon-beta-la in moderately active ulcerative colitis. Aliment Pharmacol Ther. 2008 Sep 15;28(6):758-67. doi: 10.1111/j.1365-2036.2008.03778.x.
Results Reference
result
Links:
URL
http://www.mslifelines.com
Description
Full FDA approved prescribing information can be found here

Learn more about this trial

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

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