A Phase 3, Randomized, Open-label, Parallel-group, Multicenter Trial to Evaluate the Safety and Efficacy of Infliximab (REMICADE®) in Pediatric Subjects with Moderately to Severely Active Ulcerative Colitis

Conditions: lcerative colitis
MedDRA version: 8.1Level: LLTClassification code 10045365Term: Ulcerative colitis

Registration Number: EUCTR2006-000410-20-NL

Lead Sponsor: Centocor BV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

Condensed:
1. Are 6 to 16 years old, inclusive, if enrolled at a site that cannot treat and/or follow subjects once they become 18 years of age.
OR
Are 6 to 17 years old, inclusive, at all other sites.
2. Have moderately to severely active UC, defined as a baseline Mayo score of 6 to 12, inclusive.
3. Had UC diagnosed at least 3 months prior to screening.
4. Must have the diagnosis of UC confirmed by the screening biopsy.
5. Must have moderately to severely active UC confirmed during the screening sigmoidoscopy by a = 2 endoscopy subscore of the Mayo score.
6. Must meet at least 1 of the following criteria:
a. Immunomodulators (6-MP or AZA):
1) Be receiving adequate treatment* with 6-MP or AZA.
OR
2) Have failed to respond to an adequate dose of 6-MP or AZA.
OR
3) Have had medical complications and/or AEs from 6-MP or AZA that preclude the use of these medications at doses adequate to treat UC.
OR
b. Oral Corticosteroids:
1) Be receiving with oral corticosteroids.
OR
2) Have failed to respond to an adequate dose of corticosteroids or to successfully taper corticosteroids.
OR
3) Have had medical complications and/or AEs from corticosteroids that preclude the use of these medications.
7. Must be receiving 6-MP, AZA, or MTX because of the potential of these drugs to prevent the formation of antibodies to infliximab.
8. Must meet concomitant medication stability criteria, as appropriate:
a. 6-MP, AZA, MTX:
1) Must have been receiving 1 of the immunomodulatory agents 6-MP, AZA, or MTX for 8 weeks prior to assessment of the baseline Mayo score.
2) If 6-MP, AZA, or MTX has been recently discontinued, it must have been stopped at least 4 weeks prior to Mayo screening procedures.
b. Corticosteroids:
1) If receiving oral or rectal corticosteroids, the dose must have been stable for at least 2 weeks prior to Mayo screening procedures.
2) If oral or rectal corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to Mayo screening procedures.
c. 5-ASA compounds:
1) If receiving oral or rectal 5-ASA compounds, the dose must have been stable for at least 2 weeks prior to Mayo screening procedures.
2) If oral or rectal 5-ASA compounds have been recently discontinued, they must have been stopped at least 2 weeks prior to Mayo screening procedures.
d. Bulking or stool softening agents: If using bulking or stool softening agents chronically, the dose must have been stable for at least 2 weeks prior to Mayo screening procedures and a stable dose must be maintained until Week 54.
9. If receiving enteral nutrition, must have been on a stable regimen for 2 weeks prior to Mayo screening procedures.
10. Must have discontinued the use of antibiotics for the treatment of UC at least 3 weeks prior to Mayo screening procedures.
11. Must have at least 1 of the following:
a. A well-documented history of chicken pox by medical chart review or careful interview of parents or guardian, OR
b. An uncertain history of chicken pox with a positive varicella antibody titer, OR
c. A history of varicella vaccination with positive varicella antibody titer.
12. If at increased risk for colon cancer must either have had a colonoscopy to assess the presence of dysplasia within 1 year prior to the first infusion at Week 0 or a colonoscopy to assess the presence of malignancy at the screening visit
13. Have screening laboratory tests that meet the following criteria:
a. Hemoglobin = 8.5 g/dL
b. White blood cell count = 3.5 x 10E9/L
c.

Exclusion Criteria

Condensed:
1. Have severe extensive colitis as evidenced by:
a. Investigator judgment that the subject is likely to require colectomy within 12 weeks of baseline.
OR
b. Symptom complex at screening or baseline visits that includes at least 4 of the following:
1) diarrhea with = 6 bowel movements/day with macroscopic blood in stool
2) focal severe or rebound abdominal tenderness
3) persistent fever (= 37.5°C)
4) tachycardia (= 90 beats/minute)
5) anemia (= 8.5 g/dL)
2. Have UC limited to the rectum only or to < 20 cm of the colon.
3. Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.
4. Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.
5. Have had a chest radiograph within 3 months prior to the first administration of
study agent that shows an abnormality suggestive of a malignancy or current
active infection, including TB.
6. Have had a nontuberculous mycobacterial infection or opportunistic infection
within 6 months prior
to screening.
7. Have had a live viral or bacterial vaccination within 3 months prior to screening.
8. Have a positive stool culture for enteric pathogens
9. Have or have had serious infection in the 3 months prior to screening.
10. Have immune deficiency syndrome.
11. Have documented HIV, AIDS-related complex, or AIDS and/or hepatitis B or
hepatitis C.
12. Have signs or symptoms of any other medical condition that might predispose the
subject to significant infection.
13. Receiving total parenteral nutrition within the 2 weeks prior to Mayo screening procedures.
14. Received parenteral corticosteroids within 2 weeks prior to Mayo screening procedures.
15. Require chronic and frequent use of antimotility agents for control of diarrhea
16. Have used laxatives, except for preparation for endoscopy or other procedures,
within 1 week prior to Mayo screening procedures.
17. Were treated with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil
within 8 weeks prior to screening.
18. Have used any investigational drug within 4 weeks prior to screening or within
5 half-lives of the investigational agent, whichever is longer.
19. Have received prior treatment with infliximab or any other TNF antagonist
20. Have known history of allergy to murine proteins or any previous treatment with
murine products.
21. Have ever received natalizumab or other agents that target alpha-4-integrin.
22. Have ever received agents that deplete B cells or T cells.
23. Presence of a stoma.
24. Presence or history of a fistula.
25. Require, or required within the 2 months prior to screening, 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 benefit from infliximab treatment.
26. Have severe, fixed symptomatic stenosis of the large or small intestine.
27. Presence or history of colonic obstruction within the 6 months prior to baseline,
confirmed by objective radiographic or endoscopic evidence of a stricture with
resulting obstruction.
28. History of extensive colonic resection that would prevent adequate evaluation of the effect of infliximab on clinical disease activity.
29. History of colonic mucosal dysplasia.
30. Presence on screening endoscopy of adenomatous colonic polyps, if not removed
prior to study entry, or history of adenomatous colonic polyps that were

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: to evaluate the efficacy of a 3-dose induction regimen of infliximab in inducing a clinical response in pediatric subjects with moderately to severely active UC and to evaluate the safety profile of infliximab during induction and maintenance treatment.;Secondary Objective: 1. To evaluate the efficacy of 2 infliximab maintenance dosing regimens (q8 and q12 weeks) in maintaining clinical remission.<br>2. To evaluate the efficacy of 2 infliximab maintenance dosing regimens (q8 and q12 weeks) in maintaining clinical response.<br>3. To evaluate the efficacy of a 3-dose induction regimen of infliximab in inducing clinical remission.<br>4. To evaluate the efficacy of a 3-dose induction regimen of infliximab in inducing mucosal healing.;Primary end point(s): Clinical response at Week 8

Secondary Outcome Measures

Name	Time	Method

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