Crohn's Disease
Conditions
Brief summary
The purpose of this study is to demonstrate the efficacy and safety of adalimumab for the induction of clinical remission in Japanese subjects with Crohn's disease.
Interventions
BIOLOGICALadalimumab
160 mg at Week 0, 80 mg at Week 2
BIOLOGICALplacebo
Placebo at Week 0 and Week 2
Sponsors
Abbott Japan Co.,Ltd
Eisai Co., Ltd.
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Crohn's Disease Activity Index (CDAI) score of \>= 220 and \<= 450 * If subjects have previously been administered infliximab, subjects who discontinued use due to a loss of response or intolerance to infliximab therapy
Exclusion criteria
* Ulcerative colitis or indeterminate colitis * History of cancer, lymphoma, leukemia or lymphoproliferative disease, active tuberculosis (TB), or Human immunodeficiency virus (HIV) * Body weight is below 30 kg * Surgical bowel resections within the past 6 months * Females who are pregnant or breast-feeding or considering becoming pregnant during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Subjects With a Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) at Week 4 | 4 Weeks | CDAI is used to quantify the symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score above 450 indicates severe disease. Comparison of the number of subjects with a clinical remission (CDAI \< 150) in the adalimumab 160 mg (Week 0)/ 80 mg (Week 2) and adalimumab 80 mg (Week 0)/ 40 mg (Week 2) groups at Week 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission (CDAI < 150) at Week 2 | Week 2 | Number of subjects in each treatment group in clinical remission (CDAI \< 150) in Full Analysis Set (FAS) using non-responder Imputation (NRI) at Week 2. |
| Clinical Response (CR-70 and CR-100) in Period A | Weeks 2 and Week 4 | The number of subjects in each treatment group with a clinical response 70 (CDAI decrease of \>=70 compared to Baseline) and 100 (CDAI decrease of \>=100 compared to Baseline) at Week 2 and Week 4. |
| Clinical Response (CR-70 and CR-100) in Period B | Week 6 and Week 8 | The Number of subjects in each treatment group with a CR-70 (CDAI decrease of \>= 70 compared to Baseline) and 100 (CDAI decrease of \>= 100 compared to Baseline) in subjects who were non-responders at Week 4 at Week 6 and Week 8. |
| Clinical Remission (CDAI <150) at Week 6 and Week 8 | Week 6 and Week 8 | The number of subjects with clinical remission (CDAI \< 150) in the subjects who were non-responders at Week 4 calculated with non-responder imputation (NRI) at Week 6 and Week 8 |
Countries
Japan
Participant flow
Recruitment details
Subjects with moderate to severe Crohn's Disease (Crohn's Disease Activity Index \[CDAI\] \>= 220 and \<= 450) were enrolled into study. The period from the first dose of study drug to the evaluation at Week 4 is Period A. The period from the study drug injection at Week 4 to the evaluation at Week 8 is Period B.
Pre-assignment details
All subjects were evaluated at Week 4. If responders (CDAI decrease \>= 70 points compared to Baseline), rolled over to a maintenance study. If non-responders (CDAI decrease of \< 70 points compared to Baseline), continued in study and received: adalimumab 160/80 mg + 40/40 mg, or adalimumab 80/40 mg + 40/40 mg or placebo + adalimumab 160/80 mg.
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab 160 mg/80 mg Adalimumab 160 mg at Week 0, 80 mg at Week 2 | 33 |
| Adalimumab 80 mg/40 mg Adalimumab 80 mg at Week 0, 40 mg at Week 2 | 34 |
| Placebo Placebo at Week 0, placebo Week 2 | 23 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period A - Week 0 - Week 4 | Adverse Event | 1 | 2 | 0 | 0 |
| Period B - Week 4 - Week 8 | Adverse Event | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Adalimumab 160 mg/80 mg | Adalimumab 80 mg/40 mg | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 32.0 years STANDARD_DEVIATION 9.6 | 30.6 years STANDARD_DEVIATION 9.26 | 30.4 years STANDARD_DEVIATION 6.93 | 31.1 years STANDARD_DEVIATION 8.8 |
| Region of Enrollment Japan | 33 participants | 34 participants | 23 participants | 90 participants |
| Sex: Female, Male Female | 13 Participants | 18 Participants | 7 Participants | 38 Participants |
| Sex: Female, Male Male | 20 Participants | 16 Participants | 16 Participants | 52 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / — | 15 / — | 8 / — | 5 / — | 9 / — | 8 / — |
| serious Total, serious adverse events | 1 / — | 3 / — | 2 / — | 1 / — | 1 / — | 0 / — |
Outcome results
Primary
The Number of Subjects With a Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) at Week 4
CDAI is used to quantify the symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score above 450 indicates severe disease. Comparison of the number of subjects with a clinical remission (CDAI \< 150) in the adalimumab 160 mg (Week 0)/ 80 mg (Week 2) and adalimumab 80 mg (Week 0)/ 40 mg (Week 2) groups at Week 4.
Time frame: 4 Weeks
Population: The primary analysis will be performed on the full analysis set (randomized subjects who received at least one dose of study drug) using the non-responder imputation for missing remission observations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab 160 mg/80 mg | The Number of Subjects With a Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) at Week 4 | 11 Particpants |
| Adalimumab 80 mg/40 mg | The Number of Subjects With a Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) at Week 4 | 6 Particpants |
| Placebo | The Number of Subjects With a Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) at Week 4 | 3 Particpants |
Secondary
Clinical Remission (CDAI < 150) at Week 2
Number of subjects in each treatment group in clinical remission (CDAI \< 150) in Full Analysis Set (FAS) using non-responder Imputation (NRI) at Week 2.
Time frame: Week 2
Population: Subjects with a clinical remission (CDAI \<= 150) in the adalimumab 160 mg (Week 0/80 mg (Week 2) and adalimumab 80 mg (Week 0)/40 mg (Week 2) in full analysis set using Non-responder Imputation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab 160 mg/80 mg | Clinical Remission (CDAI < 150) at Week 2 | Week 2 | 6 Participants |
| Adalimumab 80 mg/40 mg | Clinical Remission (CDAI < 150) at Week 2 | Week 2 | 5 Participants |
| Placebo | Clinical Remission (CDAI < 150) at Week 2 | Week 2 | 1 Participants |
Secondary
Clinical Remission (CDAI <150) at Week 6 and Week 8
The number of subjects with clinical remission (CDAI \< 150) in the subjects who were non-responders at Week 4 calculated with non-responder imputation (NRI) at Week 6 and Week 8
Time frame: Week 6 and Week 8
Population: Subjects who were rated as non-responders (CDAI reduction \< 70) in the evaluation of clinical remission (CDAI\<150) at Week 4. For Week 6 and Week 8 descriptive statistics performed only for non-responders at Week 4 in the three treatment groups: adalimumab 160/80 mg + 40/40 mg, adalimumab 80/40 mg + 40/40 mg, and placebo + adalimumab 160/80 mg.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab 160 mg/80 mg | Clinical Remission (CDAI <150) at Week 6 and Week 8 | Clinical Remission at Week 6 | 0 Participants |
| Adalimumab 160 mg/80 mg | Clinical Remission (CDAI <150) at Week 6 and Week 8 | Clinical Remission at Week 8 | 0 Participants |
| Adalimumab 80 mg/40 mg | Clinical Remission (CDAI <150) at Week 6 and Week 8 | Clinical Remission at Week 6 | 1 Participants |
| Adalimumab 80 mg/40 mg | Clinical Remission (CDAI <150) at Week 6 and Week 8 | Clinical Remission at Week 8 | 1 Participants |
| Placebo | Clinical Remission (CDAI <150) at Week 6 and Week 8 | Clinical Remission at Week 6 | 2 Participants |
| Placebo | Clinical Remission (CDAI <150) at Week 6 and Week 8 | Clinical Remission at Week 8 | 2 Participants |
Secondary
Clinical Response (CR-70 and CR-100) in Period A
The number of subjects in each treatment group with a clinical response 70 (CDAI decrease of \>=70 compared to Baseline) and 100 (CDAI decrease of \>=100 compared to Baseline) at Week 2 and Week 4.
Time frame: Weeks 2 and Week 4
Population: The secondary efficacy analysis was performed using descriptive statistics in randomized subjects who received at least one dose of study drug (full analysis set) in the three treatment groups: Adalimumab 160 mg/80 mg, adalimumab 80mg/40 mg, and placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab 160 mg/80 mg | Clinical Response (CR-70 and CR-100) in Period A | CR-70 at Week 2 | 15 participants |
| Adalimumab 160 mg/80 mg | Clinical Response (CR-70 and CR-100) in Period A | CR-70 at Week 4 | 23 participants |
| Adalimumab 160 mg/80 mg | Clinical Response (CR-70 and CR-100) in Period A | CR-100 at Week 2 | 10 participants |
| Adalimumab 160 mg/80 mg | Clinical Response (CR-70 and CR-100) in Period A | CR-100 at Week 4 | 15 participants |
| Adalimumab 80 mg/40 mg | Clinical Response (CR-70 and CR-100) in Period A | CR-100 at Week 4 | 17 participants |
| Adalimumab 80 mg/40 mg | Clinical Response (CR-70 and CR-100) in Period A | CR-70 at Week 2 | 17 participants |
| Adalimumab 80 mg/40 mg | Clinical Response (CR-70 and CR-100) in Period A | CR-100 at Week 2 | 11 participants |
| Adalimumab 80 mg/40 mg | Clinical Response (CR-70 and CR-100) in Period A | CR-70 at Week 4 | 20 participants |
| Placebo | Clinical Response (CR-70 and CR-100) in Period A | CR-100 at Week 4 | 4 participants |
| Placebo | Clinical Response (CR-70 and CR-100) in Period A | CR-70 at Week 4 | 7 participants |
| Placebo | Clinical Response (CR-70 and CR-100) in Period A | CR-100 at Week 2 | 2 participants |
| Placebo | Clinical Response (CR-70 and CR-100) in Period A | CR-70 at Week 2 | 4 participants |
Secondary
Clinical Response (CR-70 and CR-100) in Period B
The Number of subjects in each treatment group with a CR-70 (CDAI decrease of \>= 70 compared to Baseline) and 100 (CDAI decrease of \>= 100 compared to Baseline) in subjects who were non-responders at Week 4 at Week 6 and Week 8.
Time frame: Week 6 and Week 8
Population: Full analysis set - subjects rated as non-responders (did not attain CDAI reduction \>= 70) in the evaluation of CR-70 and CR-100 at Week 4. For Week 6 and Week 8 descriptive statistics performed only for non-responders at Week 4 in the three treatment groups: adalimumab 160/80 mg + 40/40 mg, adalimumab 80/40 mg + 40/40 mg, and placebo + 160/80 mg.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab 160 mg/80 mg | Clinical Response (CR-70 and CR-100) in Period B | CR-70 at Week 6 | 1 Participants |
| Adalimumab 160 mg/80 mg | Clinical Response (CR-70 and CR-100) in Period B | CR-70 at Week 8 | 3 Participants |
| Adalimumab 160 mg/80 mg | Clinical Response (CR-70 and CR-100) in Period B | CR-100 at Week 6 | 0 Participants |
| Adalimumab 160 mg/80 mg | Clinical Response (CR-70 and CR-100) in Period B | CR-100 at Week 8 | 0 Participants |
| Adalimumab 80 mg/40 mg | Clinical Response (CR-70 and CR-100) in Period B | CR-100 at Week 8 | 2 Participants |
| Adalimumab 80 mg/40 mg | Clinical Response (CR-70 and CR-100) in Period B | CR-70 at Week 6 | 4 Participants |
| Adalimumab 80 mg/40 mg | Clinical Response (CR-70 and CR-100) in Period B | CR-100 at Week 6 | 1 Participants |
| Adalimumab 80 mg/40 mg | Clinical Response (CR-70 and CR-100) in Period B | CR-70 at Week 8 | 5 Participants |
| Placebo | Clinical Response (CR-70 and CR-100) in Period B | CR-100 at Week 8 | 7 Participants |
| Placebo | Clinical Response (CR-70 and CR-100) in Period B | CR-70 at Week 8 | 12 Participants |
| Placebo | Clinical Response (CR-70 and CR-100) in Period B | CR-100 at Week 6 | 3 Participants |
| Placebo | Clinical Response (CR-70 and CR-100) in Period B | CR-70 at Week 6 | 9 Participants |