Comparison of the Efficacy and Safety of Infliximab, as Monotherapy or in Combination With Azathioprine, Versus Azathioprine Monotherapy in Moderate to Severe Active Ulcerative Colitis (Part 1). Comparison of Maintenance Versus Intermittent Infliximab Treatment in Maintaining Remission: A Follow-up of Efficacy and Safety (Part 2) - UC SUCCESS

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2006-002670-22-SK
• Date of registration: 15/04/2008
• Prospective Registration: No
• Primary sponsor: Schering-Plough Research Institute, a division of Schering Corporation
• Public title: Comparison of the Efficacy and Safety of Infliximab, as Monotherapy or in Combination With Azathioprine, Versus Azathioprine Monotherapy in Moderate to Severe Active Ulcerative Colitis (Part 1). Comparison of Maintenance Versus Intermittent Infliximab Treatment in Maintaining Remission: A Follow-up of Efficacy and Safety (Part 2) - UC SUCCESS
• Scientific title: Comparison of the Efficacy and Safety of Infliximab, as Monotherapy or in Combination With Azathioprine, Versus Azathioprine Monotherapy in Moderate to Severe Active Ulcerative Colitis (Part 1). Comparison of Maintenance Versus Intermittent Infliximab Treatment in Maintaining Remission: A Follow-up of Efficacy and Safety (Part 2) - UC SUCCESS
• Date of first enrolment: 08/02/2008
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002670-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: yes; Double blind: yes; Parallel group: yes; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): Therapeutic exploratory (Phase II): Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV):

Countries of recruitment

Belgium, Czech Republic, France, Germany, Hungary, Italy, Portugal, Slovakia, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
The subject must meet ALL the criteria listed below for entry:
1. Must be =18 years of age at the time of informed consent, of either sex, and of any race;
2. Must have endoscopic evidence of UC, as determined by sigmoidoscopy, within 14 days prior to Baseline;
3. Must have a total Mayo score of 6 to 12 points at Baseline;
4. Must have responded inadequately to corticosteroid treatment (ie, the last or current UC flare did not respond adequately to a standard course of corticosteroids) with or without 5 aminosalicylic acid (5-ASA);
5. Must be off corticosteroids or on a stable dose of corticosteroid for at least 2 weeks prior to enrollment. The maximal daily dose of corticosteroid at Baseline must not exceed the equivalent of 30 mg of prednisone;
6. Must be naïve to infliximab and other tumor necrosis factor-alpha (TNF-a) antagonists;
7. Must be either naïve to AZA/6-MP or have not received AZA/6-MP for at least 3 months before enrollment in the study;
8 Are considered eligible according to the following tuberculosis (TB) screening criteria:
a. Have no history of latent or active TB prior to Screening;
b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination;
c. Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of infliximab;
d. Within 1 month prior to the first administration of inflixmab, either have negative tuberculin skin test, as outlined in Appendix 6 OR have a newly identified positive tuberculin test during screening in which active TB has been ruled out, and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of infliximab.
e. Must have a chest X-ray (posterior-anterior and lateral views), taken within the 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.
9. Who have had UC for more than 10 years should have had a full colonoscopy within 2 years prior to Screening for the surveillance of dysplasia;
10. Subjects’ Screening and Baseline clinical laboratory tests (complete blood count [CBC] and blood chemistries) must be within the following parameters:
a. White blood cells (WBCs) =3.5 x 10 power of 9/L
b. Neutrophils =1.5 x 10 power of 9/L
c. Platelets =100 x 10 power of 9/L
d. Serum creatinine <1.5 mg/dL (or <133 µmol/L)
e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =1.5 x upper limit of normal (ULN), alkaline phosphatase and gamma-glutamyltransferase =2.5 x ULN
f. Total bilirubin =1 x ULN
11. Subjects who had been on antibiotics for the treatment of UC (eg, ciprofloxacin and metronidazole) must have been discontinued from them at least 3 weeks prior to Screening;
12. Must be free of any clinically significant condition or situation, other than UC that, i
Exclusion criteria:
The subject will be excluded from entry if ANY of the criteria listed below are met:
1. Have severe extensive colitis as evidenced by:
a. Investigator judgment that the subject is likely to require colectomy within 12 wks of Baseline
OR
b. Subjects with at least 4 of these symptoms at Screening or Baseline visits as described in the protocol.
2. Require, or are required within the 2 mths prior to baseline, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage or other conditions possibly confounding the evaluation of disease activity;
3. Have severe, fixed symptomatic stenosis of the large or small intestine;
4. Have current evidence of colonic obstruction or history within the 6 mths prior to baseline, confirmed with objective radiographic or endoscopic evidence of a stricture with resulting
5. Have a history of colonic mucosal dysplasia;
6. Presence on screening endoscopy of adenomatous colonic polyps, if not removed prior to study entry, or history of adenomatous colonic polyps that were not removed;
7. Have the presence of a stoma;
8. Have a history of extensive colonic resection that would prevent adequate evaluation of clinical disease activity
9. Have a positive stool culture for enteric pathogens, pathogenic ova or parasites within 4 months prior to Baseline unless subject has received treatment and had a negative stool examination 1 wk or longer after the end of treatment;
10. Have a concomitant diagnosis of CHF, including medically controlled asymptomatic subjects;
11. Have had serious infections within 2 mths of screening. Less serious infections need not be considered as an exclusion at the discretion of the investigator;
12. Have had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to screening;
13. Have a known infection with HIV and/or hepatitis B or hepatitis C;
14. Have a history of a known allergy to murine proteins or allergy/sensitivity to study drug or its excipients;
15. Have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases;
16. Have a known history of demyelinating disease suggestive of multiple sclerosis or optic neuritis;
17. Presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening);
18. Have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly;
19. Have any current known malignancy or malignancy within 5 years prior to screening (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence);
20. Have poor tolerability of venipuncture or lack of adequate venous access for required blood sa

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

Health Condition(s) or Problem(s) studied

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

Intervention(s)

Trade Name: Remicade
Product Name: Remicade
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Infliximab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Powder for concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Imuran
Product Name: Overencapsulated Azathioprine (Imuran) 50 mg Tablet
Product Code: SCH 900050
Pharmaceutical Form: Capsule*
INN or Proposed INN: azathioprine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Part 1 of this study are:
- To compare the proportion of subjects with moderate to severe active UC who achieve remission at Wk 16 on infliximab monotherapy versus AZA monotherapy.
- To compare the proportion of subjects with moderate to severe active UC who achieve remission at Wk 16 on IFX/AZA combination therapy versus IFX monotherapy.
Secondary objectives for Part 2 are:
- To assess the long-term safety and efficacy of maintenance versus intermittent therapy with 5 mg/kg IFX in a moderate to severe active UC population.
-To assess mucosal healing
- To determine the number of colectomies.
- To determine the number of hospitalizations and unscheduled physician visits and surgeries due to UC.
- To determine the number and outcome of surgical procedures due to UC.
- To determine antibody formation to IFX in subjects who receive IFX monotherapy or IFX/AZA combination therapy as intermittent or maintenance IFX treatment in Part 2.

Main Objective: There are 2 parts. The primary objective of Part 1 of this study is to compare the proportion of subjects with moderate to severe active UC who achieve remission at Wk 16 on IFX/AZA combination therapy versus AZA monotherapy. Clinical remission at Wk 16 is defined as a total Mayo score of 2 points or lower, with no individual subscore exceeding one point, without the use of corticosteroids. The primary objective of Part 2 of this study is to determine whether remission in UC is better sustained by maintenance (q8w) or intermittent (upon relapse) infliximab treatment.

Primary end point(s): The primary efficacy endpoint for Part 1 of the study is the proportion of subjects in remission at Wk 16 (ie, total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point, without the use of corticosteroids).The primary efficacy endpoint for Part 2 is the average remission rate over duration of treatment.

Secondary ID(s)

P04807

2006-002670-22-DE

N/A

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 28/04/2016
• Date Completed: 16/02/2010
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-002670-22/results