A Study of the Safety and Efficacy of Infliximab(REMICADE ) in Pediatric Patients With Moderately to SeverelyActive Ulcerative Colitis

• Sponsor: Centocor, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00336492
• Collaborator: (none)
• Enrollment: 60
• Locations: 27
• Arms: 2
• Duration (Months): 43
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the effectiveness and safety of infliximab (Remicade) in children with moderately to severely active ulcerative colitis.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Biological: infliximab; Biological: infliximab; Biological: infliximab; Biological: infliximab	Phase 3

Detailed Description

Ulcerative Colitis (UC) is a disorder involving the lining of the colon. A substance called "tumor necrosis factor" (TNF) naturally occurs in the body. TNF is thought to play an important role in the development of ulcerative colitis by causing some of the damage that is seen in the colon. "Antibodies" are normally made in the body and help fight off infection. Infliximab is an antibody that is made in a scientific laboratory, using parts of both mouse and human antibodies. It has been designed to attach to TNF, making it difficult for TNF to do any damage. This study will be done at centers in North America and Europe. Each child will first have a clinic visit (screening visit) to have some tests done to make sure the child is the type of patient who should be in this study. At the 2nd visit (week 0), the child will have the first treatment with infliximab. All children in the study will receive 5 mg/kg infliximab 3 times (at weeks 0, 2 and 6) over the first 6 weeks of the study. If the child's symptoms do not improve by the 8th week, the child will receive no further infusions, but will return for safety evaluations. If the child's symptoms do improve, the child will be randomly assigned (like the flip of a coin) to either 5 mg/kg infliximab every 8 weeks through week 46 or 5 mg/kg infliximab every 12 weeks through week 42. If the child gets worse after being randomly assigned, the amount of infliximab may be increased or the infliximab may be given more frequently. A final infusion will be given at either week 42 or week 46. There will be a safety evaluation at week 54 and a visit at week 62 to get a blood sample. Patients will receive 5 mg/kg of infliximab at weeks 0, 2 and 6 and then 5mg/kg infliximab either every 8 weeks or 12 weeks until weeks 42 or 46. Infliximab is given as an intravenous infusion over 2 hours.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 002 infliximab infusion of 5mg/kg at weeks 0, 2, 6 followed by every 12 wks through week 42; infliximab - Could receive infusion of 10mg/kg every 8 weeks up to week 42; infliximab - Could receive infusion of 5mg/kg every 8 weeks up to week 42	Biological: infliximab; infusion of 5mg/kg at weeks 0, 2, 6 followed by every 12 wks through week 42; infliximab - Could receive infusion of 10mg/kg every 8 weeks up to week 42; infliximab - Could receive infusion of 5mg/kg every 8 weeks up to week 42; Biological: infliximab; infliximab - Could receive infusion of 10 mg/kg every 8 weeks up to week 42
Experimental: 001 infliximab infusion of 5mg/kg at weeks 0, 2, 6 followed by every 8 wks through week 46; infliximab - Could receive infusion of 10mg/kg every 8 weeks up to week 46	Biological: infliximab; infusion of 5mg/kg at weeks 0, 2, 6 followed by every 8 wks through week 46; infliximab - Could receive infusion of 10mg/kg every 8 weeks up to week 46; Biological: infliximab; infusion of 5mg/kg at weeks 0, 2, 6, then every 12 wks through week 42

Outcome Measures

Primary Outcome Measures

1. The Number of Participants With Clinical Response at Week 8 [Week 8]

   Range is 0 to 12 points, where 0 is the least disease activity, and 12 is the most disease activity. Clinical response at Week 8 is defined as a decrease from baseline in the Mayo score(based on symptoms of ulcerative colitis) by >=30% and >= 3 points, with a decrease in the rectal bleeding subscore >=1 or a rectal bleeding subscore of 0 or 1. Treatment failure rules (patients who discontinued study agent due to lack of therapeutic effect, had a colectomy or ostomy, or had protocol-prohibited medication changes) were applied to determine the final clinical response status for each patient.

Secondary Outcome Measures

1. The Number of Participants With Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission at Week 54 [Week 54]

   Range is 0 to 85 points, where 0 is the least disease activity, and 85 is the most disease activity. Remission is a score <10. In addition to the PUCAI remission status, treatment failure rules (patients who discontinued study agent due to lack of therapeutic effect, had a colectomy or ostomy, had protocol-prohibited medication changes, or stepped up) were applied to determine the final PUCAI.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have moderately to severely active ulcerative colitis

• Diagnosed with ulcerative colitis for 2 weeks before screening

• Male patients who are sexually active and female patients who are sexually active or of childbearing potential must use adequate birth control while participation in the study and for 6 months after the last infusion.

Exclusion Criteria:

• History of latent or active TB

• Have had a live viral or bacterial vaccination within 3 months before screening

• Have or have had serious infections within 3 months before screening

• Prior treatment with infliximab

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Phoenix	Arizona	United States
3		Los Angeles	California	United States
4		Denver	Colorado	United States
5		Hartford	Connecticut	United States
6		Orlando	Florida	United States
7		Atlanta	Georgia	United States
8		Chicago	Illinois	United States
9		Indianapolis	Indiana	United States
10		Boston	Massachusetts	United States
11		Rochester	Minnesota	United States
12		New Hyde Park	New York	United States
13		Durham	North Carolina	United States
14		Cleveland	Ohio	United States
15		Columbus	Ohio	United States
16		Dayton	Ohio	United States
17		Providence	Rhode Island	United States
18		Milwaukee	Wisconsin	United States
19		Antwerpen		Belgium
20		Leuven		Belgium
21		Vancouver N/A	British Columbia	Canada
22		Hamilton	Ontario	Canada
23		Toronto	Ontario	Canada
24		Edmonton		Canada
25		Halifax		Canada
26		Hvidovre N/A		Denmark
27		Rotterdam		Netherlands

Sponsors and Collaborators

• Centocor, Inc.

Investigators

• Study Director: Centocor, Inc. Clinical Trial, Centocor, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Study of the Safety and Efficacy of Infliximab(REMICADE ) in Pediatric Subjects with Moderately to SeverelyActive Ulcerative Colitis

Publications

None provided.

• Responsible Party: Centocor, Inc.
• ClinicalTrials.gov Identifier: NCT00336492
• Other Study ID Numbers: CR012388; C0168T72
• First Posted: Jun 13, 2006
• Last Update Posted: Jul 30, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Centocor, Inc.: Ulcerative colitis; inflammatory bowel disease; children
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Infliximab

Study Results

Participant Flow

Arm/Group Title	Not Randomized Group	5 mg/kg Infliximab Every 8 Wks	5 mg/kg Infliximab Every 12 Wks
Arm/Group Description	Participants who were not randomized at Week 8	Participants who were clinical responders at Week 8 who were randomized to 5 mg/kg Infliximab every 8 wks	Participants who were clinical responders at Week 8 who were randomized to 5 mg/kg Infliximab every 12 wks
Period Title: Overall Study
STARTED	15	22	23
COMPLETED	0	18	12
NOT COMPLETED	15	4	11

Baseline Characteristics

Arm/Group Title	Not Randomized Group	5 mg/kg Infliximab Every 8 Wks	5 mg/kg Infliximab Every 12 Wks	Total
Arm/Group Description	Participants who were not randomized at Week 8	Participants who were clinical responders at Week 8 who were randomized to 5 mg/kg Infliximab every 8 wks	Participants who were clinical responders at Week 8 who were randomized to 5 mg/kg Infliximab every 12 wks	Total of all reporting groups
Overall Participants	15	22	23	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.9 (2.64)	13.7 (3.20)	14.2 (3.03)	13.4 (3.10)
Sex: Female, Male (Count of Participants)
Female	7 46.7%	12 54.5%	13 56.5%	32 53.3%
Male	8 53.3%	10 45.5%	10 43.5%	28 46.7%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants With Clinical Response at Week 8
Description	Range is 0 to 12 points, where 0 is the least disease activity, and 12 is the most disease activity. Clinical response at Week 8 is defined as a decrease from baseline in the Mayo score(based on symptoms of ulcerative colitis) by >=30% and >= 3 points, with a decrease in the rectal bleeding subscore >=1 or a rectal bleeding subscore of 0 or 1. Treatment failure rules (patients who discontinued study agent due to lack of therapeutic effect, had a colectomy or ostomy, or had protocol-prohibited medication changes) were applied to determine the final clinical response status for each patient.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

The primary efficacy endpoint analysis was based on all treated participants.

Arm/Group Title	Infliximab 5 mg/kg
Arm/Group Description	Infliximab 5 mg/kg group
Measure Participants	60
Number [Participants]	44 293.3%

2. Secondary Outcome

Title	The Number of Participants With Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission at Week 54
Description	Range is 0 to 85 points, where 0 is the least disease activity, and 85 is the most disease activity. Remission is a score <10. In addition to the PUCAI remission status, treatment failure rules (patients who discontinued study agent due to lack of therapeutic effect, had a colectomy or ostomy, had protocol-prohibited medication changes, or stepped up) were applied to determine the final PUCAI.
Time Frame	Week 54

Outcome Measure Data

Analysis Population Description

PUCAI remission at Week 54 analysis was based on all participants randomized at Week 8 who were evaluable for PUCAI. Fifteen participants discontinued Infliximab treatment.

Arm/Group Title	5 mg/kg Infliximab Every 8 Wks	5 mg/kg Infliximab Every 12 Wks
Arm/Group Description	Participants who were clinical responders at Week 8 who were randomized to 5 mg/kg Infliximab every 8 wks	Participants who were clinical responders at Week 8 who were randomized to 5 mg/kg Infliximab every 12 wks
Measure Participants	21	22
Number [Participants]	8 53.3%	4 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Infliximab 5 mg/kg, 5 mg/kg Infliximab Every 12 Wks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.146
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Adverse Event Reporting Description	Data for subjects who stepped up are included according to the regimen received before step-up.
Arm/Group Title	Not Randomized Group		5 mg/kg Infliximab Every 8 Wks		5 mg/kg Infliximab Every 12 Wks
Arm/Group Description	Participants who were not randomized at Week 8		Participants who were clinical responders at Week 8 who were randomized to 5 mg/kg Infliximab every 8 wks		Participants who were clinical responders at Week 8 who were randomized to 5 mg/kg Infliximab every 12 wks
All Cause Mortality
	Not Randomized Group		5 mg/kg Infliximab Every 8 Wks		5 mg/kg Infliximab Every 12 Wks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Not Randomized Group		5 mg/kg Infliximab Every 8 Wks		5 mg/kg Infliximab Every 12 Wks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/15 (33.3%)		4/22 (18.2%)		5/23 (21.7%)
Blood and lymphatic system disorders
Anemia	0/15 (0%)		1/22 (4.5%)		0/23 (0%)
Neutropenia	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Gastrointestinal disorders
Colitis Ulcerative	4/15 (26.7%)		2/22 (9.1%)		3/23 (13%)
Pancreatitis	0/15 (0%)		1/22 (4.5%)		0/23 (0%)
Infections and infestations
Cellulitis	0/15 (0%)		1/22 (4.5%)		0/23 (0%)
Infection	0/15 (0%)		1/22 (4.5%)		0/23 (0%)
Infection Viral	0/15 (0%)		1/22 (4.5%)		0/23 (0%)
Renal and urinary disorders
Urinary Tract Infection	0/15 (0%)		0/22 (0%)		1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Pharyngitis	0/15 (0%)		0/22 (0%)		1/23 (4.3%)
Pneumonia Lobar	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Not Randomized Group		5 mg/kg Infliximab Every 8 Wks		5 mg/kg Infliximab Every 12 Wks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/15 (66.7%)		19/22 (86.4%)		22/23 (95.7%)
Blood and lymphatic system disorders
Anemia	0/15 (0%)		4/22 (18.2%)		2/23 (8.7%)
Thrombocythemia	0/15 (0%)		0/22 (0%)		2/23 (8.7%)
Gastrointestinal disorders
Abdominal Pain	3/15 (20%)		3/22 (13.6%)		2/23 (8.7%)
Blood in Stool	1/15 (6.7%)		0/22 (0%)		1/23 (4.3%)
Colitis Ulcerative	1/15 (6.7%)		7/22 (31.8%)		15/23 (65.2%)
Nausea	0/15 (0%)		2/22 (9.1%)		1/23 (4.3%)
Stomatitis Ulcerative	0/15 (0%)		2/22 (9.1%)		0/23 (0%)
Vomiting	1/15 (6.7%)		1/22 (4.5%)		2/23 (8.7%)
General disorders
Chest Pain	1/15 (6.7%)		0/22 (0%)		1/23 (4.3%)
Chills	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Pain	1/15 (6.7%)		0/22 (0%)		4/23 (17.4%)
Hepatobiliary disorders
Hepatic Enzymes Increased	0/15 (0%)		0/22 (0%)		2/23 (8.7%)
Infections and infestations
Fever	1/15 (6.7%)		6/22 (27.3%)		1/23 (4.3%)
Infection Bacterial	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Inflammation	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Influenza	0/15 (0%)		1/22 (4.5%)		2/23 (8.7%)
Influenza-Like Symptoms	0/15 (0%)		0/22 (0%)		2/23 (8.7%)
Metabolism and nutrition disorders
Hypokalemia	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Malnutrition	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Nervous system disorders
Headache	2/15 (13.3%)		3/22 (13.6%)		3/23 (13%)
Psychiatric disorders
Anxiety	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Thinking Abnormal	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Renal and urinary disorders
Urinary Tract Infection	0/15 (0%)		1/22 (4.5%)		2/23 (8.7%)
Respiratory, thoracic and mediastinal disorders
Bronchitis	0/15 (0%)		2/22 (9.1%)		0/23 (0%)
Coughing	1/15 (6.7%)		2/22 (9.1%)		3/23 (13%)
Dyspnea	0/15 (0%)		2/22 (9.1%)		1/23 (4.3%)
Pharyngitis	3/15 (20%)		4/22 (18.2%)		4/23 (17.4%)
Sinusitis	1/15 (6.7%)		2/22 (9.1%)		0/23 (0%)
Throat Tightness	1/15 (6.7%)		0/22 (0%)		0/23 (0%)
Upper Respiratory Tract Infection	1/15 (6.7%)		7/22 (31.8%)		6/23 (26.1%)
Skin and subcutaneous tissue disorders
Eczema	0/15 (0%)		2/22 (9.1%)		0/23 (0%)
Rash	0/15 (0%)		2/22 (9.1%)		1/23 (4.3%)
Vascular disorders
Hemorrhoids	1/15 (6.7%)		0/22 (0%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.