Crohn's Disease
Conditions
Keywords
Infliximab, REMICADE, Crohn's disease
Brief summary
The purpose of this study is to assess the efficacy, safety and pharmacokinetics after administration of 10mg/kg TA-650 every 8 weeks to patients with Crohn's disease showing an insufficient response to previous treatment with 5 mg/kg of REMICADE every 8 weeks.
Interventions
DRUGTA-650
(1) Screening Period: 5 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at week 0. If patients do not meet the Eligibility Criteria at week 8, they will be administered 5 mg/kg of TA-650 at week 8. (2) Increased Dose Period: 10 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours every 8 weeks for 32 weeks.
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with Crohn's disease * Patients who have relapsed with symptoms associated with Crohn's disease within 8 weeks in spite of maintenance treatment with 5mg/kg REMICADE every 8 weeks, and who are judged to be showing an insufficient response to the previous treatment by their physician
Exclusion criteria
* Severe intestinal strictures (which may have an effect on the number of loose stools or diarrhea or dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy), a diagnosis of short bowel syndrome, or previous stoma surgery * The presence of significant internal fistula (possibility that surgery might be needed, etc.) is confirmed * A history of a serious infusion reaction to REMICADE * Pregnant, lactating, and probably pregnant women * Patients who have participated in other trials and have been administered other investigational products within 12 weeks before consent * Patients judged to be inadequate to participate in this study by their physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Crohn's Disease Activity Index (CDAI) Change From Week 0 to Week 8 in the Increased Dose Period | Increased Dose Period (Week 0 to Week 8) | To confirm the decrease in median CDAI at week 8 by ≥ 50 points compared to the CDAI score at week 0 in the increased dose period. In the indication of CDAI change, decrease in CDAI was expressed by positive numbers. CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. CDAI scores generally range from 0 to 600 points. Clinical remission = CDAI \< 150 points. Moderate disease = CDAI 220 - 450 points. Severe disease = CDAI \> 450 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CDAI at Each Evaluation Time Point in the Increased Dose Period | Increased Dose Period (every 4 weeks for up to 40 weeks) | CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. CDAI scores generally range from 0 to 600 points. Clinical remission = CDAI \< 150 points. Moderate disease = CDAI 220 - 450 points. Severe disease = CDAI \> 450 points. |
| CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Increased Dose Period (every 4 weeks for up to 40 weeks) | CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. CDAI scores generally range from 0 to 600 points. Clinical remission = CDAI \< 150 points. Moderate disease = CDAI 220 - 450 points. Severe disease = CDAI \> 450 points. |
| CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Increased Dose Period (every 4 weeks for up to 40 weeks) | To confirm the decrease in median CDAI at week 8 by ≥ 50 points compared to the CDAI score at week 0 in the increased dose period. In the indication of CDAI change, decrease in CDAI was expressed by positive numbers. CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. CDAI scores generally range from 0 to 600 points. Clinical remission = CDAI \< 150 points. Moderate disease = CDAI 220 - 450 points. Severe disease = CDAI \> 450 points. |
| Serum Concentration of TA-650 at Each Time Point | Screening Period (every 4 weeks for up to 16 weeks), Increased Dose Period (every 4 weeks for up to 40 weeks), a total of 56 weeks | — |
| Antibody to TA-650 Determination | Screening Period (Week 0 to Week 16), Increased Dose Period (Week 0 to Week 40) | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TA-650 | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Increased Dose Period | Adverse Event | 4 |
| Increased Dose Period | Lack of Efficacy | 7 |
| Increased Dose Period | Pregnancy | 1 |
| Increased Dose Period | Withdrawal by Subject | 1 |
| Screening Period | Adverse Event | 1 |
| Screening Period | Lack of Efficacy | 2 |
| Screening Period | Pregnancy | 1 |
| Screening Period | Responder | 2 |
Baseline characteristics
| Characteristic | TA-650 |
|---|---|
| Age, Continuous | 29.5 years STANDARD_DEVIATION 7.3 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 45 | 25 / 45 | 29 / 39 |
| serious Total, serious adverse events | 9 / 45 | 2 / 45 | 8 / 39 |
Outcome results
Primary
Median Crohn's Disease Activity Index (CDAI) Change From Week 0 to Week 8 in the Increased Dose Period
To confirm the decrease in median CDAI at week 8 by ≥ 50 points compared to the CDAI score at week 0 in the increased dose period. In the indication of CDAI change, decrease in CDAI was expressed by positive numbers. CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. CDAI scores generally range from 0 to 600 points. Clinical remission = CDAI \< 150 points. Moderate disease = CDAI 220 - 450 points. Severe disease = CDAI \> 450 points.
Time frame: Increased Dose Period (Week 0 to Week 8)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TA-650 | Median Crohn's Disease Activity Index (CDAI) Change From Week 0 to Week 8 in the Increased Dose Period | 95.0 units on a scale |
Secondary
Antibody to TA-650 Determination
Time frame: Screening Period (Week 0 to Week 16), Increased Dose Period (Week 0 to Week 40)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TA-650 | Antibody to TA-650 Determination | Negative | 23.1 percentage of participants |
| TA-650 | Antibody to TA-650 Determination | Positive | 5.1 percentage of participants |
| TA-650 | Antibody to TA-650 Determination | Inconclusive | 71.8 percentage of participants |
| Increased Dose Period | Antibody to TA-650 Determination | Negative | 17.9 percentage of participants |
| Increased Dose Period | Antibody to TA-650 Determination | Positive | 5.1 percentage of participants |
| Increased Dose Period | Antibody to TA-650 Determination | Inconclusive | 76.9 percentage of participants |
Secondary
CDAI at Each Evaluation Time Point in the Increased Dose Period
CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. CDAI scores generally range from 0 to 600 points. Clinical remission = CDAI \< 150 points. Moderate disease = CDAI 220 - 450 points. Severe disease = CDAI \> 450 points.
Time frame: Increased Dose Period (every 4 weeks for up to 40 weeks)
Population: One patient whose data after week 4 in the increased dose period was missing was excluded from the analysis. Patients whose the outcome measure were not assessed at a time point due to dropout were excluded from the analysis of the time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 0 | 296.5 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 4 | 119.0 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 8 | 194.0 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 12 | 126.0 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 16 | 182.0 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 20 | 121.0 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 24 | 197.5 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 28 | 105.0 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 32 | 163.0 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 36 | 141.0 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 40 | 148.5 units on a scale |
| TA-650 | CDAI at Each Evaluation Time Point in the Increased Dose Period | Week 40 (the last time point) | 210.5 units on a scale |
Secondary
CDAI Change at Each Evaluation Time Point in the Increased Dose Period
To confirm the decrease in median CDAI at week 8 by ≥ 50 points compared to the CDAI score at week 0 in the increased dose period. In the indication of CDAI change, decrease in CDAI was expressed by positive numbers. CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. CDAI scores generally range from 0 to 600 points. Clinical remission = CDAI \< 150 points. Moderate disease = CDAI 220 - 450 points. Severe disease = CDAI \> 450 points.
Time frame: Increased Dose Period (every 4 weeks for up to 40 weeks)
Population: One patient whose data after week 4 in the increased dose period was missing was excluded from the analysis. Patients whose the outcome measure were not assessed at a time point due to dropout were excluded from the analysis of the time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 4 | 163.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 8 | 95.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 12 | 161.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 16 | 95.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 20 | 164.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 24 | 100.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 28 | 156.5 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 32 | 110.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 36 | 139.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to Week 40 | 95.0 units on a scale |
| TA-650 | CDAI Change at Each Evaluation Time Point in the Increased Dose Period | Week 0 to 40(last measurable time point) | 87.0 units on a scale |
Secondary
CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period
CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. CDAI scores generally range from 0 to 600 points. Clinical remission = CDAI \< 150 points. Moderate disease = CDAI 220 - 450 points. Severe disease = CDAI \> 450 points.
Time frame: Increased Dose Period (every 4 weeks for up to 40 weeks)
Population: Patients whose the outcome measure were not assessed at a time point due to dropout were excluded from the analysis of the time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 4 | 59.5 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 8 | 39.4 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 12 | 70.0 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 16 | 31.0 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 20 | 58.6 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 24 | 28.6 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 28 | 60.7 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 32 | 37.0 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 36 | 59.3 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 40 | 50.0 percentage of participants |
| TA-650 | CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period | Week 40 (the last time point) | 41.0 percentage of participants |
Secondary
Serum Concentration of TA-650 at Each Time Point
Time frame: Screening Period (every 4 weeks for up to 16 weeks), Increased Dose Period (every 4 weeks for up to 40 weeks), a total of 56 weeks
Population: Patients whose the outcome measure were not assessed at a time point due to dropout were excluded from the analysis of the time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 8 | 1.29 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | Screening Period (SP), Week 0 (pre-dose) | 1.12 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | SP, 1 hr after treatment end for week 0 | 97.74 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | SP, Week 4 | 4.93 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | SP, Week 8 | 0.30 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | SP, Week 12 | 5.25 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | SP, Week 16 | 0.79 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | Increased dose Period(IP), Week0 (pre-dose) | 0.30 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, 1 hr after treatment end for week 0 | 191.24 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 4 | 9.93 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 12 | 11.20 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 16 (pre-dose) | 1.31 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, 1hr after administration at week 16 | 203.16 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 20 | 8.71 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 24 | 1.83 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 28 | 9.97 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 32 | 1.60 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 36 | 12.72 μg/mL |
| TA-650 | Serum Concentration of TA-650 at Each Time Point | IP, Week 40 | 2.18 μg/mL |