Trial Outcomes & Findings for Infliximab to Treat Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease (NCT NCT00325078)
NCT ID: NCT00325078
Last Updated: 2015-12-29
Results Overview
Number of Infections from Baseline to 1 year
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
40 participants
Primary outcome timeframe
Baseline to 1 year
Results posted on
2015-12-29
Participant Flow
Participant milestones
| Measure |
Treatment Group
This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.
Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.
|
Observation Group
CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections.
|
Control Volunteer
Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
7
|
25
|
|
Overall Study
COMPLETED
|
3
|
2
|
23
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Infliximab to Treat Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease
Baseline characteristics by cohort
| Measure |
Treatment Group
n=8 Participants
This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.
Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.
|
Observation Group
n=7 Participants
CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections.
|
Control Volunteer
n=25 Participants
Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
36 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
33 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
36 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
29 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline to 1 yearPopulation: The volunteer group includes patients with chronic granulomatous disease as well as healthy normal volunteers as controls. Infection rates only pertain to and are counted in subjects with underlying immunodeficiency (chronic granulomatous disease).
Number of Infections from Baseline to 1 year
Outcome measures
| Measure |
Treatment
n=8 Participants
This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.
Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.
|
Observation
n=7 Participants
Subjects with IBD without TNFa inhibitor treatment
|
Control Volunteers
n=8 Participants
Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
|
|---|---|---|---|
|
Safety of Study Drug
|
5 infections
|
4 infections
|
13 infections
|
PRIMARY outcome
Timeframe: Baseline, 1 yearPopulation: All participants in the Treatment and Observation Arms with collected CDAI data. The CDAI, a tool validated for Crohn's disease is not applicable to healthy donors or CGD patients without IBD, and therefore not measured in the Control participants.
Measured participant Crohn's disease Activity Index (CDAI) values. The CDAI is a tool comprised of clinical and laboratory factors such as stool frequency, consistency, abdominal pain, general well being, weight and blood profile as an objective measure of disease activity. A higher score corresponds to greater severity of inflammatory bowel disease; severe disease conventionally defined as \>450, a remission as \<150, and a response to treatment as a fall of CDAI of \>70 points. Infections and IBD are not expected in healthy control subjects. The greater the score, the more severe the disease, and a score of less than 5 represents clinical remission.
Outcome measures
| Measure |
Treatment
n=5 Participants
This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.
Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.
|
Observation
n=5 Participants
Subjects with IBD without TNFa inhibitor treatment
|
Control Volunteers
Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
|
|---|---|---|---|
|
Efficacy of Treatment With Study Drug
CDAI Value #1 at Baseline
|
114.4 Crohn's disease activity Index
|
17.5 Crohn's disease activity Index
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #2 at Baseline
|
191 Crohn's disease activity Index
|
22.5 Crohn's disease activity Index
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #3 at Baseline
|
329.8 Crohn's disease activity Index
|
53 Crohn's disease activity Index
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #4 at Baseline
|
505.2 Crohn's disease activity Index
|
159 Crohn's disease activity Index
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #5 at Baseline
|
516 Crohn's disease activity Index
|
266.7 Crohn's disease activity Index
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #1 at 1 year
|
95.5 Crohn's disease activity Index
|
NA Crohn's disease activity Index
Only patients who completed the year of study drug treatment got a repeat CDAI
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #2 at 1 year
|
138 Crohn's disease activity Index
|
NA Crohn's disease activity Index
Only patients who completed the year of study drug treatment got a repeat CDAI
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #3 at 1 year
|
185.4 Crohn's disease activity Index
|
NA Crohn's disease activity Index
Only patients who completed the year of study drug treatment got a repeat CDAI
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #4 at 1 year
|
259.2 Crohn's disease activity Index
|
NA Crohn's disease activity Index
Only patients who completed the year of study drug treatment got a repeat CDAI
|
—
|
|
Efficacy of Treatment With Study Drug
CDAI Value #5 at 1 year
|
295.2 Crohn's disease activity Index
|
NA Crohn's disease activity Index
Only patients who completed the year of study drug treatment got a repeat CDAI
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 yearGut Immune cell types and their cytokine profile
Outcome measures
Outcome data not reported
Adverse Events
Treatment Group
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Observation Group
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Control Volunteer
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment Group
n=8 participants at risk
This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.
Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.
|
Observation Group
n=7 participants at risk
CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections.
|
Control Volunteer
n=25 participants at risk
Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
|
|---|---|---|---|
|
Infections and infestations
lung infection
|
12.5%
1/8
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/7
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/25
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
|
Nervous system disorders
Nervous system disorders - drug overdose
|
12.5%
1/8
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/7
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/25
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
Other adverse events
| Measure |
Treatment Group
n=8 participants at risk
This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.
Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.
|
Observation Group
n=7 participants at risk
CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections.
|
Control Volunteer
n=25 participants at risk
Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.
|
|---|---|---|---|
|
Gastrointestinal disorders
diarrhea (clostridium diff)
|
12.5%
1/8
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/7
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/25
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
|
General disorders
Infusion related reaction
|
25.0%
2/8
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/7
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/25
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
|
Surgical and medical procedures
Infections and infestations, IV line infection
|
0.00%
0/8
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
14.3%
1/7
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
0.00%
0/25
The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.
|
Additional Information
De Ravin, SukSee
National Institute of Allergy and Infectious Diseases
Phone: +1 301 496 6772
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place