Crohn's Disease
Conditions
Keywords
Interleukin-12, Inflammation, Research study, Ustekinumab, CNTO1275, Interleukin-23
Brief summary
A medical research study in adult patients who have moderate to severe Crohn's disease designed to determine whether or not treatment with an experimental drug called ustekinumab (or CNTO1275) is safe or not and to determine if the treatment will reduce the symptoms of Crohn's disease.
Detailed description
In Crohn's disease there is inflammation (changes in body tissue which normally happen during injury or infection) and or ulceration (open sores) in the intestines.This occurs because the immune system (the part of the body that fights off infection) has an abnormal and overactive response against the intestine and bowel tissues of the body. Crohn's disease is usually treated with medications that either directly decrease inflammation or decrease the general activity of the immune system to improve the diarrhea, abdominal pain, and other symptoms of Crohn's Disease. Ustekinumab antibodies (natural substances made by your immune system to stick to and help remove foreign materials in your body that cause diseases) have been created to stick to and block the activity of two of the immune substances thought to cause abnormal inflammation of Crohn's disease. Patients who are eligible and who have received Remicade, Humira, or Cimzia and failed or been intolerant to one of these drugs will be randomized to either active drug (ustekinumab) or placebo. All patients will be randomized (like flipping a coin) at week 0 to be in one of 4 groups. At week 0 the study drug will be given by IV administration and at weeks 8 and 16 by subcutaneous injection. There will be 11 study visits in total and the study will continue until week 36. Blood and stool samples will be collected and studied, questionnaires to check on how you are doing in terms of your disease will be completed, an Electrocardiogram (EKG) obtained, safety evaluations conducted and diary cards distributed to be completed during the entire study. One of 4 groups: Grp 1-placebo, Grp 2-active drug 1mg/kg IV, Grp 3-active drug 3mg/kg IV, Grp 4-active drug 6mg/kg IV. Based on the clinical response status at Week 6, patients from Grps 2, 3 and 4 will be re-randomized at week 8 to receive either placebo or 90 mg SC at both weeks 8 and 16 and patients from Grp 1 will receive placebo at Week 8 and Week 16 or a 270 mg SC injection at Week 8 and 90 mg SC at Week 16.
Interventions
DRUGUstekinumab 6 mg/kg (IP)
Induction phase (Week 0-8) (IP) - Ustekinumab 6mg/kg IV group
DRUGPlacebo (IP)
Induction phase (Week 0-8) (IP) - Placebo IV group
DRUGUstekinumab 1mg/kg (IP)
Induction phase (Week 0-8) (IP) - Ustekinumab 1 mg/kg IV group
DRUGUstekinumab 3 mg/kg (IP)
Induction phase (Week 0-8) (IP) - Ustekinumab 3mg/kg IV group
DRUGPlacebo IV - Responder - Placebo SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Placebo IV at Week 0 - Responder at week 6 - Receiving Placebo SC at Week 8 and Week 16
DRUGPlacebo IV - Nonresponder - Ustekinumab 270/90 mg SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Placebo IV at Week 0 - Nonresponder at week 6 - Receiving Ustekinumab 270 mg SC at Week 8 and 90 mg at Week 16
DRUGUstekinumab IV - Responder - Placebo SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Responder at week 6 - Receiving Placebo SC at Week 8 and Week 16
DRUGUstekinumab IV - Responder - Ustekinumab 90mg SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Responder at week 6 - Receiving Ustekinumab 90 mg SC at Week 8 and Week 16
DRUGUstekinumab IV - Nonresponder - Placebo SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Nonresponder at week 6 - Receiving Placebo SC at Week 8 and Week 16
DRUGUstekinumab IV - Nonresponder - Ustekinumab 90mg SC (MP)
Maintenance phase (Week 8-36) (MP) - Receiving Ustekinumab IV at Week 0 - Nonresponder at week 6 - Receiving Ustekinumab 90 mg SC at Week 8 and Week 16
Sponsors
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have Crohn's disease or fistulizing Crohn's disease of at least 3 months duration * Must have received Remicade, adalimumab or Cimzia at a dose approved for the treatment of Crohn's disease * Must have failed or been intolerant to Remicade, Humira or Cimzia for treatment of Crohn's disease * Must be 18 years of age or older * Must have active Crohn's disease according to the Crohn's Disease Activity Index (CDAI \> =220 and \< =450).
Exclusion criteria
* Patients who have had any kind of bowel resection, diversions or placement of a stoma within 6 months * Are pregnant, nursing or planning pregnancy (both men and women) while enrolled in the study or within 1 year after receiving study agent * Patients who have received Remicade, Humira or Cimzia \< =8 weeks before the first administration of study drug * Patients with certain complications of Crohn's disease that would make it hard to assess response to study drug * Patients with a history of or ongoing chronic or recurrent infectious disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response at Week 6 | Baseline to Week 6 | As measured by the Crohn's Disease Activity Index (CDAI). CDAI scores range from 0 points (minimal disease activity) to over 600 points (severe disease activity). Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of \< 150 was attained. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response at Week 4 | Baseline to Week 4 | As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of \< 150 was attained. |
| Number of Participants With Clinical Response at Week 8 | Baseline to Week 8 | As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of \< 150 was attained. |
| Number of Participants With Clinical Remission at Week 6 | Baseline to Week 6 | As measured by a CDAI score of \< 150 points. |
| Number of Participants With Clinical Remission at Week 22 (Among Responders From Week 6) | Baseline to Week 22 | As measured by a CDAI score of \< 150 points. |
| Number of Participants With Clinical Response at Week 22 (Among Responders From Week 6) | Baseline to Week 22 | As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of \< 150 was attained. |
| Number of Participants With Clinical Remission at Week 8 | Baseline to Week 8 | As measured by a CDAI score of \< 150 points. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Israel, Netherlands, New Zealand, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (IP) Induction phase (Week 0-8) (IP) - Placebo IV group | 132 |
| Ustekinumab 1 mg/kg (IP) Induction phase (Week 0-8) (IP) - Ustekinumab 1mg/kg IV group | 131 |
| Ustekinumab 3 mg/kg (IP) Induction phase (Week 0-8) (IP) - Ustekinumab 3mg/kg IV group | 132 |
| Ustekinumab 6 mg/kg (IP) Induction phase (Week 0-8) (IP) - Ustekinumab 6mg/kg IV group | 131 |
| Total | 526 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Induction Phase | Adverse Event | 5 | 2 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Phase | Lack of Efficacy | 9 | 2 | 4 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Phase | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Phase | Other | 4 | 6 | 3 | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Phase | Adverse Event | 0 | 0 | 0 | 0 | 1 | 3 | 5 | 1 | 8 | 7 |
| Maintenance Phase | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 | 3 | 3 | 2 | 11 | 7 |
| Maintenance Phase | Other | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 2 | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo (IP) | Ustekinumab 1 mg/kg (IP) | Ustekinumab 3 mg/kg (IP) | Ustekinumab 6 mg/kg (IP) | Total |
|---|---|---|---|---|---|
| Age Continuous | 39.5 years STANDARD_DEVIATION 13.05 | 38.8 years STANDARD_DEVIATION 11.95 | 38.2 years STANDARD_DEVIATION 12.63 | 39.4 years STANDARD_DEVIATION 13.21 | 39 years STANDARD_DEVIATION 12.69 |
| Sex: Female, Male Female | 68 Participants | 83 Participants | 75 Participants | 83 Participants | 309 Participants |
| Sex: Female, Male Male | 64 Participants | 48 Participants | 57 Participants | 48 Participants | 217 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 132 | 51 / 130 | 50 / 133 | 47 / 131 | 18 / 28 | 47 / 85 | 39 / 73 | 39 / 72 | 64 / 110 | 52 / 109 |
| serious Total, serious adverse events | 11 / 132 | 6 / 130 | 8 / 133 | 9 / 131 | 8 / 28 | 16 / 85 | 12 / 73 | 9 / 72 | 21 / 110 | 22 / 109 |
Outcome results
Primary
Number of Participants With Clinical Response at Week 6
As measured by the Crohn's Disease Activity Index (CDAI). CDAI scores range from 0 points (minimal disease activity) to over 600 points (severe disease activity). Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of \< 150 was attained.
Time frame: Baseline to Week 6
Population: All participants who were randomized, regardless of whether they received study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (IP) | Number of Participants With Clinical Response at Week 6 | 31 Participants |
| Ustekinumab 1 mg/kg (IP) | Number of Participants With Clinical Response at Week 6 | 48 Participants |
| Ustekinumab 3 mg/kg (IP) | Number of Participants With Clinical Response at Week 6 | 45 Participants |
| Ustekinumab 6 mg/kg (IP) | Number of Participants With Clinical Response at Week 6 | 52 Participants |
p-value: 0.005Cochran-Mantel-Haenszel
p-value: 0.057Cochran-Mantel-Haenszel
p-value: 0.021Cochran-Mantel-Haenszel
Secondary
Number of Participants With Clinical Remission at Week 22 (Among Responders From Week 6)
As measured by a CDAI score of \< 150 points.
Time frame: Baseline to Week 22
Population: All participants who were randomized, regardless of whether they received study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (IP) | Number of Participants With Clinical Remission at Week 22 (Among Responders From Week 6) | 20 Participants |
| Ustekinumab 1 mg/kg (IP) | Number of Participants With Clinical Remission at Week 22 (Among Responders From Week 6) | 30 Participants |
p-value: 0.029Cochran-Mantel-Haenszel
Secondary
Number of Participants With Clinical Remission at Week 6
As measured by a CDAI score of \< 150 points.
Time frame: Baseline to Week 6
Population: All participants who were randomized, regardless of whether they received study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (IP) | Number of Participants With Clinical Remission at Week 6 | 14 Participants |
| Ustekinumab 1 mg/kg (IP) | Number of Participants With Clinical Remission at Week 6 | 21 Participants |
| Ustekinumab 3 mg/kg (IP) | Number of Participants With Clinical Remission at Week 6 | 21 Participants |
| Ustekinumab 6 mg/kg (IP) | Number of Participants With Clinical Remission at Week 6 | 16 Participants |
p-value: 0.682Cochran-Mantel-Haenszel
p-value: 0.206Cochran-Mantel-Haenszel
p-value: 0.196Cochran-Mantel-Haenszel
Secondary
Number of Participants With Clinical Remission at Week 8
As measured by a CDAI score of \< 150 points.
Time frame: Baseline to Week 8
Population: All participants who were randomized, regardless of whether they received study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (IP) | Number of Participants With Clinical Remission at Week 8 | 14 Participants |
| Ustekinumab 1 mg/kg (IP) | Number of Participants With Clinical Remission at Week 8 | 23 Participants |
| Ustekinumab 3 mg/kg (IP) | Number of Participants With Clinical Remission at Week 8 | 24 Participants |
| Ustekinumab 6 mg/kg (IP) | Number of Participants With Clinical Remission at Week 8 | 24 Participants |
p-value: 0.074Cochran-Mantel-Haenszel
p-value: 0.081Cochran-Mantel-Haenszel
p-value: 0.105Cochran-Mantel-Haenszel
Secondary
Number of Participants With Clinical Response at Week 22 (Among Responders From Week 6)
As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of \< 150 was attained.
Time frame: Baseline to Week 22
Population: All participants who were randomized, regardless of whether they received study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (IP) | Number of Participants With Clinical Response at Week 22 (Among Responders From Week 6) | 31 Participants |
| Ustekinumab 1 mg/kg (IP) | Number of Participants With Clinical Response at Week 22 (Among Responders From Week 6) | 50 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants With Clinical Response at Week 4
As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of \< 150 was attained.
Time frame: Baseline to Week 4
Population: All participants who were randomized, regardless of whether they received study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (IP) | Number of Participants With Clinical Response at Week 4 | 22 Participants |
| Ustekinumab 1 mg/kg (IP) | Number of Participants With Clinical Response at Week 4 | 36 Participants |
| Ustekinumab 3 mg/kg (IP) | Number of Participants With Clinical Response at Week 4 | 49 Participants |
| Ustekinumab 6 mg/kg (IP) | Number of Participants With Clinical Response at Week 4 | 40 Participants |
p-value: 0.008Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.035Cochran-Mantel-Haenszel
Secondary
Number of Participants With Clinical Response at Week 8
As measured by the CDAI. Clinical response was defined as a reduction from baseline of ≥ 100 points. Participants with a baseline CDAI of ≥ 220 to ≤ 248 were considered to be in clinical response if a CDAI score of \< 150 was attained.
Time frame: Baseline to Week 8
Population: All participants who were randomized, regardless of whether they received study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (IP) | Number of Participants With Clinical Response at Week 8 | 23 Participants |
| Ustekinumab 1 mg/kg (IP) | Number of Participants With Clinical Response at Week 8 | 42 Participants |
| Ustekinumab 3 mg/kg (IP) | Number of Participants With Clinical Response at Week 8 | 42 Participants |
| Ustekinumab 6 mg/kg (IP) | Number of Participants With Clinical Response at Week 8 | 57 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.007Cochran-Mantel-Haenszel
p-value: 0.006Cochran-Mantel-Haenszel