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.

• Register: EUCTR
• Last refreshed on: 13 March 2017
• Main ID: EUCTR2007-004867-22-SK
• Date of registration: 28/05/2009
• Prospective Registration: No
• Primary sponsor: Biogen Idec Ltd
• Public title: 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.
• Scientific title: 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.
• Date of first enrolment: 25/05/2009
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004867-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: yes Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Hungary, Slovakia

Key inclusion & exclusion criteria

Inclusion criteria:
Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of Screening:
1. Must give written informed consent and any authorizations required by local law (e.g., Protected Health Information).
2. Aged 18 to 65 years old, inclusive, at the time of informed consent.
3. Must have an established diagnosis of UC for =/>6 months.
4. Must have endoscopy (flexible sigmoidoscopy or colonoscopy if clinically indicated) with biopsy to confirm the diagnosis of UC.
5. Must have >20 cm of active disease at Screening endoscopy.
6. Must have active UC with a Mayo Score/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 with corticosteroids, azathioprine, 6-mercaptopurine, 5-aminosalicylic acid (5-ASA) or any combination thereof.
7. Colonoscopy within the past 5 years for extent of disease.
8. For subjects with UC for >10 years, colonoscopy with appropriate biopsies within 1 year prior to Screening to exclude dysplasia and neoplasia.
9. At the time of screening, subjects must be receiving 1 or more of the following treatments or any combination thereof, and must be willing to maintain stable doses of these treatments after randomizaation at Week 0 (Visit 1): corticosteroids, 6-mercaptopurine or azathioprine or 5-aminosalicylic acid, as follows
a: If receiving corticosteroid treatment prior to Screening, subjects must be willing to maintain stable doses until Week 8.
b: If receiving 6-mercaptopurine or azathioprine prior to screening, subjects must have taken stable doses for at least 12 weeks prior to screening, and be willing to maintain stable doses until at least Week 8.
c: If receiving 5-ASA prior to screening, subjects must have taken stable doses for at least 2 weeks prior to screening, and be willing to maintain stable doses until at least Week 12.
10. Subjects must be willing and able to comply with a 7-day UC symptom collection by IVRS telephone diary as assessed during the Screening period.
11. All male subjects and female subjects of child bearing potential must be willing and able to practice effective birth control during the study and be willing and able to continue contraception for 1 month after their last dose of study treatment.
For purposes of this study, effective contraception is defined as follows:
For females:
• Using 1 or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation), intrauterine contraception/device, hormonal contraception, or any 2 barrier methods (a combination of male or female condom with spermicide, diaphragm, sponge, cervical cap).
• Abstinence, at the discretion of the Investigator, can be considered an acceptable method of contraception. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
For males:
• Effective male contraception includes a vasectomy with negative semen analysis at follow-up, or the use of condoms with spermicide.
For purposes of this study, women of child-bearing potential (WOCBP) are defined as all women physiologically capable of becoming pregnant, UNLESS they meet the following conditions:
• Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy
Re
Exclusion criteria:
Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria exist at Screening:
1. Subjects with a diagnosis of indeterminate colitis or Crohn’s disease.
2. Subjects with clinical findings suggestive of Crohn’s disease, e.g., fistulae or granulomas on biopsy.
3. Subjects with an imminent need for surgery.
4. Subjects with toxic megacolon.
5. Subjects with primary sclerosing cholangitis.
6. Any of the following abnormal laboratory results:
• ALT and AST =/>2xULN
• Hemoglobin =/<9 g/dL
• WBC <3500 cells/mm3
• Lymphocyte count <1000 cells/microLitre
• Platelet count <100,000 cells/microLitre

7. Female subjects who are pregnant or who wish to become pregnant during the study, or who are lactating.
8. Subjects with known symptomatic colonic stricture.
9. Stool cultures positive for enteric infection, including parasitic and C. difficile infection.
10. Subjects who are positive for HBsAg, HCV, or HIV at Screening.

11. Subjects with a history of malignant disease, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
12. History of suicidal ideation within 3 months prior to Day 1 (Week 0, Visit 1) or an episode of severe depression within 3 months prior to Day1. Severe depression is defined as any episode of depression that requires hospitalization or the initiation of antidepressant therapy, or the increase in the dose of an existing regiman of antidepressant therapy. Subjects receiving ongoing antidepressant therapy are not excluded form the study unless the medication dose has been increased within 3 months prior to Day 1.
13. History of severe allergic or anaphylactic reactions.
14. History of intolerance to acetaminophen (paracetamol) that would preclude its use during the study period.
15. Subjects with a history of major abdominal surgery (e.g. gastrectomy) within the past 5 years.
16. Subjects with a history of colonic or small bowel obstruction or resection.
17. History of any clinically significant cardiac disease (including cardiomyopathy, congestive heart failure or related risk factors) or endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (including untreated or unstable seizures), dermatologic, renal, and psychiatric or other major disease, as determined by the Investigator. This includes psychosis, schizophrenia, mania, or major psychiatric illness requiring pharmacological treatment. Patients with a clinical diagnosis of anorexia nervosa or bulimia nervosa are excluded from the study.
18. Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening.
19. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within 6 months prior to Screening.
20. History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to Screening.

21. Treatment with another study treatment or approved therapy for investigational use within the 4 weeks prior to the first dose of study treatment.
22. Exposure to monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion prote

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to Severe Ulcerative Colitis
MedDRA version: 9.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis

Intervention(s)

Trade Name: Avonex
Product Name: Avonex
Pharmaceutical Form: Solution for injection
Concentration unit: µl/ml microlitre(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the clinical activity of AVONEX in subjects with moderate to severe UC.
The primary endpoint is clinical response at Week 8, defined as a decrease from baseline in the Total Mayo Score/Disease Activity Index (DAI) 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 0 or 1.

Primary end point(s): The primary endpoint is clinical response at Week 8, defined as a decrease from baseline in the Total Mayo Score/Disease Activity Index (DAI) 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 0 or 1.

Secondary Objective: The secondary objectives of this study are to determine (i) the safety and tolerability of AVONEX in subjects with moderate to severe UC, and (ii) the percentage of subjects with a decrease in the SCCAI score of =/> 3 points at Week 8.

Secondary ID(s)

108UC201

2007-004867-22-HU