Phase III Study of D9421-C 9 mg in Patients With Active Crohn's Disease in Japan

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical efficacy of D9421-C 9 mg once daily compared to Mesalazine 1 g three times a day to patients with mild to moderate active Crohn's disease affecting ileum, ileocecal region and/or ascending colon as defined by a score of 180-400 on the Crohn's Disease Activity Index (CDAI) by assessment of the remission after 8-week treatment defined by a CDAI score of ≤ 150.

Detailed Description
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A multicentre, double-blind, randomised, parallel-group, Phase III study to assess efficacy and safety of D9421-C 9 mg versus Mesalazine 3 g in patients with active Crohn's Disease (CD) in Japan

Official Title
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A Multicentre, Double-blind, Randomised, Parallel-group, Phase III Study to Assess Efficacy and Safety of D9421-C 9 mg Versus Mesalazine 3 g in Patients With Active Crohn's Disease (CD) in Japan

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: D9421-C capsule 3 mg
* Drug: Mesalazine tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 15 years of age or older Main active disease of the ileal, ileocecal region, and/or ascending colon - - If treated with partial nutrition treatment (≤1200 kcal/day) or if treated with azathioprine (≤2.0 mg/kg/day) or 6-mercaptopurine (≤1.2 mg/kg/day), prior to randomisation until the study completion or discontinuation Ability to read, write and to fill a diary card and HRQL questionnaire Having mild to moderate active Crohn's disease, defined as CDAI score of 180-400 at baseline Exclusion Criteria: Patient with CD lesion or status which may affect the evaluation of the efficacy (e.g. lesion only in the upper G-I, active anorectal lesion, abscess formation, stenosis, fistulae, ostomy, short bowel or other uncontrolled concomitant disease) Patient who need any concomitant treatment for CD that may affect the assessment for efficacy of the study drug Patient who need any medication which is prohibited due to suspected influence to metabolism of the study drug Patient who is judged to be inadequate to participate in this study from the safety point of view Patient with well-founded doubt about protocol violation

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D9421-C<br>D9421-C 9 mg once daily | Drug: D9421-C capsule 3 mg<br>* Patients randomised to D9421-C 9 mg will take 3 capsules of D9421-C capsule 3 mg once daily before breakfast and 4 tablets of Mesalazine tablets placebo three times a day after each meal for 8 weeks.<br>|
| Active Comparator: Mesalazine<br>Mesalazine 1 g three times a day | Drug: Mesalazine tablets<br>* Patients randomised to Mesalazine 3 g will take 3 capsules of D9421-C capsule placebo once daily before breakfast and 4 tablets of Mesalazine tablets 250 mg three times a day after each meal for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission After 8-week of Treatment | For the primary efficacy variable Remission after 8 weeks of treatment, Crohn's Disease Activity Index CDAI scores was used to determine the patient's response. Remission for this study is defined as a CDAI score of ≤150. A patient who drops out without any remission before week 8 was considered as a nonresponder (no remission) for this analysis. A patient who drops out before Week 8, but was in remission at the time of dropout, was considered in remission after dropout in this analysis. | 8 Week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission After 2-week of Treatment | For the secondary efficacy variable Remission after 2 weeks of treatment, Crohn's Disease Activity Index CDAI scores was used to determine the patient's response. Remission for this study is defined as a CDAI score of ≤150. | 2 Week | 
| Remission After 4-week of Treatment | For the secondary efficacy variable Remission after 4 weeks of treatment, Crohn's Disease Activity Index CDAI scores was used to determine the patient's response. Remission for this study is defined as a CDAI score of ≤150. | 4 Week | 
| Change in Observed CDAI Scores From Baseline to Weeks 2 | Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are asked to fill the following items in the diary card (from the morning in preceding day to the morning in current day). (1) Number of liquid or very soft stools (2) Abdominal pain rating (none, mild, moderate, severe) (3) General well-being (generally well, slightly under par, poor, very poor, terrible) (4) Body temperature (if a patient feels fever) (5) Intake of loperamide or other opiates for diarrhoea. The data for the calculation of CDAI score in diary card is then transcribed by the investigator(s) into the eCRFs at each clinical visit. | 2 Week | 
| Change in Observed CDAI Scores From Baseline to Weeks 4 | Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are asked to fill the following items in the diary card (from the morning in preceding day to the morning in current day). (1) Number of liquid or very soft stools (2) Abdominal pain rating (none, mild, moderate, severe) (3) General well-being (generally well, slightly under par, poor, very poor, terrible) (4) Body temperature (if a patient feels fever) (5) Intake of loperamide or other opiates for diarrhoea. The data for the calculation of CDAI score in diary card is then transcribed by the investigator(s) into the eCRFs at each clinical visit. | 4 Week | 
| Change in Observed CDAI Scores From Baseline to Weeks 8 | Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are asked to fill the following items in the diary card (from the morning in preceding day to the morning in current day). (1) Number of liquid or very soft stools (2) Abdominal pain rating (none, mild, moderate, severe) (3) General well-being (generally well, slightly under par, poor, very poor, terrible) (4) Body temperature (if a patient feels fever) (5) Intake of loperamide or other opiates for diarrhoea. The data for the calculation of CDAI score in diary card is then transcribed by the investigator(s) into the eCRFs at each clinical visit. | 8 Week | 
| Cumulative Remission Rate at Week 2 | Remission rate is defined as CDAI score of less than or equal to 150. Cumulative remission rate at Week 2 is obtained by Kaplan-Meier (KM) estimates. | 2 Week | 
| Cumulative Remission Rate at Week 4 | Remission rate is defined as CDAI score of less than or equal to 150. Cumulative remission rate at Week 4 is obtained by Kaplan-Meier (KM) estimates. | 4 Week | 
| Cumulative Remission Rate at Week 8 | Remission rate is defined as CDAI score of less than or equal to 150. Cumulative remission rate at Week 8 is obtained by Kaplan-Meier (KM) estimates. | 8 Week | 
| Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 2 | Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points. | 2 Week | 
| Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 4 | Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points. | 4 Week | 
| Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 8 | Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points. | 8 Week | 
| Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 2 | Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points. | 2 Week | 
| Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 4 | Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points. | 4 Week | 
| Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 8 | Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points. | 8 Week | 
| Change in Total IBDQ Scores From Baseline to Weeks 2 | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 2 Week | 
| Change in Total IBDQ Scores From Baseline to Weeks 4 | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 4 Week | 
| Change in Total IBDQ Scores From Baseline to Weeks 8 | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 8 Week | 
| Change in Total IBDQ Scores From Baseline to Weeks 10 | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 10 Week | 
| Change in IBDQ Scores From Baseline to Weeks 2 - Bowel Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 2 Week | 
| Change in IBDQ Scores From Baseline to Weeks 4 - Bowel Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 4 Week | 
| Change in IBDQ Scores From Baseline to Weeks 8 - Bowel Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 8 Week | 
| Change in IBDQ Scores From Baseline to Weeks 10 - Bowel Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 10 Week | 
| Change in IBDQ Scores From Baseline to Weeks 2 - Systemic Symptom | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 2 Week | 
| Change in IBDQ Scores From Baseline to Weeks 4 - Systemic Symptom | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 4 Week | 
| Change in IBDQ Scores From Baseline to Weeks 8 - Systemic Symptom | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 8 Week | 
| Change in IBDQ Scores From Baseline to Weeks 10 - Systemic Symptom | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 10 Week | 
| Change in IBDQ Scores From Baseline to Weeks 2 - Emotional Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 2 Week | 
| Change in IBDQ Scores From Baseline to Weeks 4 - Emotional Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 4 Week | 
| Change in IBDQ Scores From Baseline to Weeks 8 - Emotional Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 8 Week | 
| Change in IBDQ Scores From Baseline to Weeks 10 - Emotional Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 10 Week | 
| Change in IBDQ Scores From Baseline to Weeks 2 - Social Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 2 Week | 
| Change in IBDQ Scores From Baseline to Weeks 4 - Social Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 4 Week | 
| Change in IBDQ Scores From Baseline to Weeks 8 - Social Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 8 Week | 
| Change in IBDQ Scores From Baseline to Weeks 10 - Social Function | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 - 70), systemic symptom score (5 - 35), emotional function score (12 - 84), social function score (5 - 35) and the total score (32 - 224), with higher scores indicating more favorable outcome. | 10 Week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild to moderate active Crohn's disease, affecting ileum, ileocecal region, ascending colon, score of 180-400 on the CDAI