Crohn's Disease
Conditions
Brief summary
This study investigates safety and efficacy of CP-690,550 in adult patients with moderate to severe Crohn's disease. The study hypothesis is that at least one of the dose levels to be tested will be more effective than placebo (inactive drug).
Interventions
DRUGCP-690,550
administration via oral route twice daily
DRUGPlacebo
administration via oral route twice daily
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be at least 18 years of age at screening * Males and females with clinical evidence of Crohn's disease for at least 3 months duration at screening * Subjects with moderate to severe Crohn's Disease at baseline, as defined by a Crohn's Disease Activity Index (CDAI) score of 220-450 inclusive
Exclusion criteria
* Subjects currently receiving immunosuppressants, interferon, anti-TNFa * Subjects with evidence of hematopoietic disorders * Subjects with evidence of active or latent TB
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response 70 at Week 4 | Week 4 | Clinical response 70: defined as a reduction in Crohn's Disease Activity Index (CDAI) score from baseline of at least 70 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Clinical Remission at Week 4 | Week 4 | Clinical remission=CDAI at Week 4 less than (\<) 150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. |
| Number of Participants With Clinical Response 100 at Week 4 | Week 4 | Clinical response 100: defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. |
| Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 1, 2 | Clinical response 70: defined as a reduction in CDAI score from baseline of at least 70 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. |
| Time to First Response 70 | Week 1 through Week 4 | Clinical response 70: defined as a reduction in CDAI score from baseline of at least 70 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 , higher score indicates higher disease activity. |
| Time to First Response 100 | Week 1 through Week 4 | Clinical response 100: defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. |
| Time to First Clinical Remission | Week 1 through Week 4 | Clinical remission=CDAI \<150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. |
Countries
Belgium, Czechia, France, Hungary, Italy, Netherlands, Poland, Slovakia, South Africa, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablet matched to CP-690550 orally twice daily for 4 weeks. | 34 |
| CP-690550 1 mg CP-690550 1 milligram (mg) tablet orally twice daily for 4 weeks. | 36 |
| CP-690550 5 mg CP-690550 5 mg tablet orally twice daily for 4 weeks. | 34 |
| CP-690550 15 mg CP-690550 15 mg tablet orally twice daily for 4 weeks. | 35 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | CP-690550 1 mg | CP-690550 5 mg | CP-690550 15 mg | Total |
|---|---|---|---|---|---|
| Age Continuous | 35.7 years STANDARD_DEVIATION 12.7 | 36.6 years STANDARD_DEVIATION 12.2 | 38.7 years STANDARD_DEVIATION 10.2 | 38.1 years STANDARD_DEVIATION 11.7 | 37.3 years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 22 Participants | 11 Participants | 20 Participants | 17 Participants | 70 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 14 Participants | 18 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 34 | 18 / 36 | 19 / 34 | 22 / 35 |
| serious Total, serious adverse events | 5 / 34 | 4 / 36 | 4 / 34 | 1 / 35 |
Outcome results
Primary
Number of Participants With Clinical Response 70 at Week 4
Clinical response 70: defined as a reduction in Crohn's Disease Activity Index (CDAI) score from baseline of at least 70 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.
Time frame: Week 4
Population: Full Analysis Set (FAS): all randomized participants who had either withdrawn as treatment failure or completed at least 1 week of dosing and had at least 1 valid CDAI score during the active double-blind phase. Number of participants analyzed excluded those with missing data or who fell outside the visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinical Response 70 at Week 4 | 14 participants |
| CP-690550 1 mg | Number of Participants With Clinical Response 70 at Week 4 | 13 participants |
| CP-690550 5 mg | Number of Participants With Clinical Response 70 at Week 4 | 18 participants |
| CP-690550 15 mg | Number of Participants With Clinical Response 70 at Week 4 | 16 participants |
Secondary
Number of Participants Achieving Clinical Remission at Week 4
Clinical remission=CDAI at Week 4 less than (\<) 150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.
Time frame: Week 4
Population: FAS: all randomized participants who had either withdrawn as treatment failure or completed at least 1 week of dosing and had at least 1 valid CDAI score during the active double-blind phase. Number of participants analyzed excluded those with missing data or who fell outside the visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Achieving Clinical Remission at Week 4 | 7 participants |
| CP-690550 1 mg | Number of Participants Achieving Clinical Remission at Week 4 | 11 participants |
| CP-690550 5 mg | Number of Participants Achieving Clinical Remission at Week 4 | 8 participants |
| CP-690550 15 mg | Number of Participants Achieving Clinical Remission at Week 4 | 5 participants |
Secondary
Number of Participants With Clinical Response 100 at Week 4
Clinical response 100: defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.
Time frame: Week 4
Population: FAS: all randomized participants who had either withdrawn as treatment failure or completed at least 1 week of dosing and had at least 1 valid CDAI score during the active double-blind phase. Number of participants analyzed excluded those with missing data or who fell outside the visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinical Response 100 at Week 4 | 9 participants |
| CP-690550 1 mg | Number of Participants With Clinical Response 100 at Week 4 | 11 participants |
| CP-690550 5 mg | Number of Participants With Clinical Response 100 at Week 4 | 14 participants |
| CP-690550 15 mg | Number of Participants With Clinical Response 100 at Week 4 | 13 participants |
Secondary
Number of Participants With Clinical Response 70 at Week 1 and 2
Clinical response 70: defined as a reduction in CDAI score from baseline of at least 70 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.
Time frame: Week 1, 2
Population: FAS: all randomized participants who had either withdrawn as treatment failure or completed at least (\>=)1 week of dosing and had \>=1 valid CDAI score during active double-blind phase. Number of participants analyzed excluded those with missing data or who fell outside visit window. 'n'=participants evaluable at given time point for each group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 1 (n=34,36,32,35) | 12 participants |
| Placebo | Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 2 (n=31,36,31,35) | 10 participants |
| CP-690550 1 mg | Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 2 (n=31,36,31,35) | 15 participants |
| CP-690550 1 mg | Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 1 (n=34,36,32,35) | 9 participants |
| CP-690550 5 mg | Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 1 (n=34,36,32,35) | 11 participants |
| CP-690550 5 mg | Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 2 (n=31,36,31,35) | 13 participants |
| CP-690550 15 mg | Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 1 (n=34,36,32,35) | 9 participants |
| CP-690550 15 mg | Number of Participants With Clinical Response 70 at Week 1 and 2 | Week 2 (n=31,36,31,35) | 16 participants |
Secondary
Time to First Clinical Remission
Clinical remission=CDAI \<150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.
Time frame: Week 1 through Week 4
Population: FAS population: included all randomized participants who had either withdrawn as treatment failure or completed at least 1 week of dosing and had at least 1 valid CDAI score during the active double-blind phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Clinical Remission | NA days |
| CP-690550 1 mg | Time to First Clinical Remission | NA days |
| CP-690550 5 mg | Time to First Clinical Remission | 30.0 days |
| CP-690550 15 mg | Time to First Clinical Remission | NA days |
Secondary
Time to First Response 100
Clinical response 100: defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.
Time frame: Week 1 through Week 4
Population: FAS population: included all randomized participants who had either withdrawn as treatment failure or completed at least 1 week of dosing and had at least 1 valid CDAI score during the active double-blind phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Response 100 | NA days |
| CP-690550 1 mg | Time to First Response 100 | 30.0 days |
| CP-690550 5 mg | Time to First Response 100 | 30.0 days |
| CP-690550 15 mg | Time to First Response 100 | NA days |
Secondary
Time to First Response 70
Clinical response 70: defined as a reduction in CDAI score from baseline of at least 70 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 , higher score indicates higher disease activity.
Time frame: Week 1 through Week 4
Population: FAS population: included all randomized participants who had either withdrawn as treatment failure or completed at least 1 week of dosing and had at least 1 valid CDAI score during the active double-blind phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Response 70 | 29.0 days |
| CP-690550 1 mg | Time to First Response 70 | 30.0 days |
| CP-690550 5 mg | Time to First Response 70 | 21.0 days |
| CP-690550 15 mg | Time to First Response 70 | 29.0 days |