Crohn's Disease
Conditions
Brief summary
The purpose of this study is to characterize the safety, efficacy and dose response of BMS-945429 in subjects with moderate to severe Crohn's disease and who have had an insufficient response to conventional therapy or have failed Anti-Tumor Necrosis Factor (anti-TNF) therapy.
Interventions
BIOLOGICALPlacebo matching with BMS-945429
Injection, Intravenous (IV), 0 mg, Day One Only, One Day
BIOLOGICALBMS-945429
Injection, Intravenous (IV), 600 mg, Day One Only, One Day
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed Crohn's Disease diagnosis via radiology, endoscopy or histology within prior 12 months. Diagnosed for at least 3 months * Active Disease with Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 * Failed conventional therapy or steroid dependent
Exclusion criteria
* Diagnosed/clinical findings of Ulcerative Colitis (UC), indeterminate colitis, non colonic/ileal disease * Stricture/stenosis, Stoma, proctocolectomy, subtotal colectomy, ileorectal anastomosis * History of diverticulitis, or evidence of Gastrointestinal (GI) perforations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Clinical Remission (CDAI<150) as Measured by the Crohn's Disease Activity Index (CDAI) | At 8 weeks during the Induction Period | CDAI scores range from 0 to 600. A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease. A decrease in greater than 100 points indicates a clinically significant improvement in disease activity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 8 and Week 12 | IBDQ consists of 32 questions divided into four dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items) and social function (5 items). Every question has graded responses from 1 (worst situation) to 7 (best situation), and thus the total score is ranging from 32 to 224 with higher scores representing better quality of life. |
| Number of Participants During the Induction Period With Anti-clazakizumab Antibodies | Up to Week 12 | — |
| Percent of Participants With Clinical Response (>100 Point Decrease in CDAI) During Induction Period as Measured by CDAI | At 8 weeks during the Induction Period | CDAI scores range from 0 to 600. A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease. A decrease in greater than 100 points indicates a clinically significant improvement in disease activity |
| Observed Maximum Concentration (Cmax) of Clazakizumab During the Induction Period | Week 0 and Week 4 | — |
| Area Under the Plasma Concentration-time Curve in One Dosing Interval [AUC(TAU)] of Clazakizumab During the Induction Period | Week 0, Week 4, Week 8 | — |
| Steady-state Trough Concentration (Cmin) of Clazakizumab During the Induction Period | Week 4, Week 8 | — |
Countries
Austria, Canada, Czechia, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Mexico, Netherlands, Poland, South Korea, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Intravenous (IV), Day One Only Subcutaneous (SC), Every 4 weeks for 8 weeks | 18 |
| Clazakizumab (150 IV/100 SC) IV, 150 mg, Day One Only SC, 100 mg, Week 8 Only, One Day | 9 |
| Clazakizumab (300 IV/100 SC) IV, 300 mg, Day One Only SC, 100 mg, Week 8 Only, One Day | 9 |
| Clazakizumab (400 SC/200 SC) SC, 400 mg, Day One and Week 4 SC, 200 mg, Week 8 only, One Day | 18 |
| Clazakizumab (600 IV/200 SC) IV, 600 mg, Day One Only SC, 200 mg, Week 8 Only, One Day | 18 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 4 | 2 | 3 | 5 | 5 |
| Overall Study | Adverse Event | 1 | 1 | 2 | 2 | 0 |
| Overall Study | Discontinued study treatment | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 3 | 2 |
| Overall Study | Participant no longer meets study criteria | 0 | 2 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Clazakizumab (150 IV/100 SC) | Clazakizumab (300 IV/100 SC) | Clazakizumab (400 SC/200 SC) | Clazakizumab (600 IV/200 SC) | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 9 Participants | 8 Participants | 18 Participants | 17 Participants | 69 Participants |
| Age, Continuous | 41.1 years STANDARD_DEVIATION 11.7 | 36.3 years STANDARD_DEVIATION 14.79 | 36.2 years STANDARD_DEVIATION 17.29 | 36.3 years STANDARD_DEVIATION 10.96 | 40.9 years STANDARD_DEVIATION 11.48 | 38.6 years STANDARD_DEVIATION 12.53 |
| Sex: Female, Male Female | 14 Participants | 5 Participants | 7 Participants | 10 Participants | 9 Participants | 45 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 2 Participants | 8 Participants | 9 Participants | 27 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 9 | 1 / 9 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 1 / 18 | 2 / 9 | 3 / 9 | 8 / 18 | 2 / 18 |
| serious Total, serious adverse events | 2 / 18 | 2 / 9 | 2 / 9 | 6 / 18 | 4 / 18 |
Outcome results
Primary
Percent of Participants With Clinical Remission (CDAI<150) as Measured by the Crohn's Disease Activity Index (CDAI)
CDAI scores range from 0 to 600. A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease. A decrease in greater than 100 points indicates a clinically significant improvement in disease activity
Time frame: At 8 weeks during the Induction Period
Population: modified Intent-to-Treat (mITT) defined as all randomized and treated subjects who had a chance to reach Day 57 by the date of study termination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With Clinical Remission (CDAI<150) as Measured by the Crohn's Disease Activity Index (CDAI) | 17.6 percentage of participants |
| Clazakizumab (150 IV/100 SC) | Percent of Participants With Clinical Remission (CDAI<150) as Measured by the Crohn's Disease Activity Index (CDAI) | 33.3 percentage of participants |
| Clazakizumab (300 IV/100 SC) | Percent of Participants With Clinical Remission (CDAI<150) as Measured by the Crohn's Disease Activity Index (CDAI) | 0 percentage of participants |
| Clazakizumab (400 SC/200 SC) | Percent of Participants With Clinical Remission (CDAI<150) as Measured by the Crohn's Disease Activity Index (CDAI) | 18.8 percentage of participants |
| Clazakizumab (600 IV/200 SC) | Percent of Participants With Clinical Remission (CDAI<150) as Measured by the Crohn's Disease Activity Index (CDAI) | 12.5 percentage of participants |
Secondary
Area Under the Plasma Concentration-time Curve in One Dosing Interval [AUC(TAU)] of Clazakizumab During the Induction Period
Time frame: Week 0, Week 4, Week 8
Population: The interpretation of the PK analysis is limited for several reasons. First, the concentration data that was collected only allowed for reporting of Cmin concentrations. Second, the sample size was limited.
Secondary
Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score
IBDQ consists of 32 questions divided into four dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items) and social function (5 items). Every question has graded responses from 1 (worst situation) to 7 (best situation), and thus the total score is ranging from 32 to 224 with higher scores representing better quality of life.
Time frame: Week 8 and Week 12
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 8 | 11.8 score on a scale | Standard Deviation 23.01 |
| Placebo | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 12 | 10.0 score on a scale | Standard Deviation 33.65 |
| Clazakizumab (150 IV/100 SC) | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 8 | -2.0 score on a scale | Standard Deviation 28.93 |
| Clazakizumab (150 IV/100 SC) | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 12 | 21.8 score on a scale | Standard Deviation 34.62 |
| Clazakizumab (300 IV/100 SC) | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 8 | 1.9 score on a scale | Standard Deviation 36.46 |
| Clazakizumab (300 IV/100 SC) | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 12 | 1.4 score on a scale | Standard Deviation 61.06 |
| Clazakizumab (400 SC/200 SC) | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 12 | 20.1 score on a scale | Standard Deviation 36.32 |
| Clazakizumab (400 SC/200 SC) | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 8 | 15.5 score on a scale | Standard Deviation 32.01 |
| Clazakizumab (600 IV/200 SC) | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 8 | 14.8 score on a scale | Standard Deviation 33.7 |
| Clazakizumab (600 IV/200 SC) | Change From Baseline at Week 8 and 12 of Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 12 | 18.7 score on a scale | Standard Deviation 35.62 |
Secondary
Number of Participants During the Induction Period With Anti-clazakizumab Antibodies
Time frame: Up to Week 12
Population: mITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants During the Induction Period With Anti-clazakizumab Antibodies | 0 participants |
| Clazakizumab (150 IV/100 SC) | Number of Participants During the Induction Period With Anti-clazakizumab Antibodies | 0 participants |
| Clazakizumab (300 IV/100 SC) | Number of Participants During the Induction Period With Anti-clazakizumab Antibodies | 0 participants |
| Clazakizumab (400 SC/200 SC) | Number of Participants During the Induction Period With Anti-clazakizumab Antibodies | 0 participants |
| Clazakizumab (600 IV/200 SC) | Number of Participants During the Induction Period With Anti-clazakizumab Antibodies | 1 participants |
Secondary
Observed Maximum Concentration (Cmax) of Clazakizumab During the Induction Period
Time frame: Week 0 and Week 4
Population: The interpretation of the PK analysis is limited for several reasons. First, the concentration data that was collected only allowed for reporting of Cmin concentrations. Second, the sample size was limited.
Secondary
Percent of Participants With Clinical Response (>100 Point Decrease in CDAI) During Induction Period as Measured by CDAI
CDAI scores range from 0 to 600. A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease. A decrease in greater than 100 points indicates a clinically significant improvement in disease activity
Time frame: At 8 weeks during the Induction Period
Population: mITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With Clinical Response (>100 Point Decrease in CDAI) During Induction Period as Measured by CDAI | 29.4 percentage of participants |
| Clazakizumab (150 IV/100 SC) | Percent of Participants With Clinical Response (>100 Point Decrease in CDAI) During Induction Period as Measured by CDAI | 33.3 percentage of participants |
| Clazakizumab (300 IV/100 SC) | Percent of Participants With Clinical Response (>100 Point Decrease in CDAI) During Induction Period as Measured by CDAI | 25.0 percentage of participants |
| Clazakizumab (400 SC/200 SC) | Percent of Participants With Clinical Response (>100 Point Decrease in CDAI) During Induction Period as Measured by CDAI | 31.3 percentage of participants |
| Clazakizumab (600 IV/200 SC) | Percent of Participants With Clinical Response (>100 Point Decrease in CDAI) During Induction Period as Measured by CDAI | 12.5 percentage of participants |
Secondary
Steady-state Trough Concentration (Cmin) of Clazakizumab During the Induction Period
Time frame: Week 4, Week 8
Population: Due to early termination of the study, only a limited number of PK samples were collected and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clazakizumab (300 IV/100 SC) | Steady-state Trough Concentration (Cmin) of Clazakizumab During the Induction Period | Week 4 | 21.0816 ug/mL | Standard Deviation 8.19326 |
| Clazakizumab (300 IV/100 SC) | Steady-state Trough Concentration (Cmin) of Clazakizumab During the Induction Period | Week 8 | 36.1026 ug/mL | Standard Deviation 14.49349 |