Pediatric Crohn's Disease
Conditions
Keywords
Infliximab, REMICADE, TA-650, pediatric Crohn's disease
Brief summary
The purpose of this study is to evaluate the efficacy of TA-650 using Pediatric Crohn's Disease Activity Index (PCDAI) in pediatric patients with moderate to severe Crohn's disease after TA-650 administration at a dose of 5 mg/kg at week 0, 2, and 6, then every 8 week after week 14 up to week 46, and at a dose of 10 mg/kg if the effect is attenuated. The safety and pharmacokinetics are also evaluated.
Detailed description
This is an open-label, uncontrolled, multicenter Phase 3 study conducted in Japan.
Interventions
DRUGTA-650
TA-650 will be intravenously infused at 5 mg/kg as an induction regimen at Week 0, 2, 6. For subjects who meet the responder criteria, TA-650 will be administered at 8-week intervals thereafter until week 46. If the criteria for a dosage escalation are met, TA-650 will be administered at a dosage of 10 mg/kg.
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have been diagnosed as Crohn's disease at least 3 months prior to screening. * Have active Crohn's disease despite adequate conventional therapy.
Exclusion criteria
* Patients with severe intestinal strictures (strictures which may affect the number of defecations, etc., or dilation of the colon or strictures in the proximal small bowel observed on barium radiograph, or strictures precluding the insertion of endoscope), a diagnosis of short bowel syndrome, or previous stoma surgery. * Patients who have a history of treatment with infliximab, or biological products (anti-TNFα agents and anti-IL-6 agents, etc.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Who Achieved PCDAI Response | Week 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54 | Crohn's Disease Activity Index(PCDAI) response was defined as a case where PCDAI on the evaluation day was decreased by at least 15 points compared to PCDAI in the screening period and decreased to not more than 30. PCDAI was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PCDAI Score | Week 0, 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54 | Crohn's Disease Activity Index (PCDAI) was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10). |
| Change From Baseline of PCDAI Score | Week 0, 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54 | Crohn's Disease Activity Index (PCDAI) was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10). |
| Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54 and the last time point during the period from administration of the study drug to Week 54 | Crohn's Disease Activity Index(PCDAI)-based remission was defined as a case where PCDAI on the evaluation day was decreased to not more than 10. Patients who satisfied the criterion for PCDAI response at least once in the evaluation at Week 2, 6 and 10 were defined as responders at Week 10. PCDAI was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10). |
| Serum TA-650 Concentration | After dose of Week 0 to 54 or at the timing of discontinuation. On the blood sampling day, before administration of the study drug. Week 0, 22 and 46, before administration and one hour after the administration. Week 14, 30 and 38, before administration. | Median, Min and Max of serum TA-650 concentration at each evaluation point after dose of 5 mg/kg TA-650. |
| The Percent of the Patients Who Experienced an Adverse Event | Until the last time point during the period from administration of the study drug to Week 54 | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TA-650 This group represents patients who received at least one dose of TA-650 5 mg/kg or 10 mg/kg.
TA-650 was intravenously infused at a dose of 5 mg/kg at Week 0, 2, 6 as an induction regimen.
For patients who met the responder criteria at Week 10, TA-650 was administered at 8-week intervals thereafter until week 46 as a maintenance regimen.
If the the criteria for a dose-increasing are met at Week 14, 22, 30, 38 or 46, TA-650 was administered at a dose of 10 mg/kg. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Maintenance Period (Week 14 to 54) | Adverse Event | 1 |
| Maintenance Period (Week 14 to 54) | Lack of Efficacy | 1 |
Baseline characteristics
| Characteristic | TA-650 |
|---|---|
| Age, Continuous | 14.5 years STANDARD_DEVIATION 1.9 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 2 / 14 |
Outcome results
Primary
Percent of Patients Who Achieved PCDAI Response
Crohn's Disease Activity Index(PCDAI) response was defined as a case where PCDAI on the evaluation day was decreased by at least 15 points compared to PCDAI in the screening period and decreased to not more than 30. PCDAI was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10).
Time frame: Week 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54
Population: 2 patients were discontinued because of an adverse event and a lack of efficacy respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 2 | 78.6 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 6 | 100.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 10 | 100.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 14 | 92.9 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 18 | 100.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 22 | 92.9 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 26 | 100.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 30 | 92.9 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 34 | 100.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 38 | 91.7 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 42 | 100.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 46 | 91.7 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 50 | 100.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | Week 54 | 91.7 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI Response | The last time point | 85.7 percentage of participants |
Secondary
Change From Baseline of PCDAI Score
Crohn's Disease Activity Index (PCDAI) was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10).
Time frame: Week 0, 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54
Population: 2 patients were discontinued because of an adverse event and a lack of efficacy respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TA-650 | Change From Baseline of PCDAI Score | Week 2 | -20.71 units on a scale | Standard Deviation 8.57 |
| TA-650 | Change From Baseline of PCDAI Score | Week 6 | -27.68 units on a scale | Standard Deviation 6.24 |
| TA-650 | Change From Baseline of PCDAI Score | Week 10 | -30.00 units on a scale | Standard Deviation 6.35 |
| TA-650 | Change From Baseline of PCDAI Score | Week 14 | -28.57 units on a scale | Standard Deviation 7.05 |
| TA-650 | Change From Baseline of PCDAI Score | Week 18 | -31.07 units on a scale | Standard Deviation 6.63 |
| TA-650 | Change From Baseline of PCDAI Score | Week 22 | -27.32 units on a scale | Standard Deviation 9.01 |
| TA-650 | Change From Baseline of PCDAI Score | Week 26 | -30.18 units on a scale | Standard Deviation 7.37 |
| TA-650 | Change From Baseline of PCDAI Score | Week 30 | -26.07 units on a scale | Standard Deviation 8.86 |
| TA-650 | Change From Baseline of PCDAI Score | Week 34 | -30.21 units on a scale | Standard Deviation 7.11 |
| TA-650 | Change From Baseline of PCDAI Score | Week 38 | -26.25 units on a scale | Standard Deviation 10.03 |
| TA-650 | Change From Baseline of PCDAI Score | Week 42 | -30.42 units on a scale | Standard Deviation 7.37 |
| TA-650 | Change From Baseline of PCDAI Score | Week 46 | -27.08 units on a scale | Standard Deviation 9.99 |
| TA-650 | Change From Baseline of PCDAI Score | Week 50 | -32.50 units on a scale | Standard Deviation 5.84 |
| TA-650 | Change From Baseline of PCDAI Score | Week 54 | -28.33 units on a scale | Standard Deviation 10.08 |
| TA-650 | Change From Baseline of PCDAI Score | The last time point | -26.25 units on a scale | Standard Deviation 10.69 |
Secondary
PCDAI Score
Crohn's Disease Activity Index (PCDAI) was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10).
Time frame: Week 0, 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, and the last time point during the period from administration of the study drug to Week 54
Population: 2 patients were discontinued because of an adverse event and a lack of efficacy respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TA-650 | PCDAI Score | Week 0 | 36.43 units on a scale | Standard Deviation 4.78 |
| TA-650 | PCDAI Score | Week 2 | 15.71 units on a scale | Standard Deviation 9.63 |
| TA-650 | PCDAI Score | Week 6 | 8.75 units on a scale | Standard Deviation 6.56 |
| TA-650 | PCDAI Score | Week 10 | 6.43 units on a scale | Standard Deviation 5.86 |
| TA-650 | PCDAI Score | Week 14 | 7.86 units on a scale | Standard Deviation 8.82 |
| TA-650 | PCDAI Score | Week 18 | 5.36 units on a scale | Standard Deviation 5.87 |
| TA-650 | PCDAI Score | Week 22 | 9.11 units on a scale | Standard Deviation 10.68 |
| TA-650 | PCDAI Score | Week 26 | 6.25 units on a scale | Standard Deviation 6.63 |
| TA-650 | PCDAI Score | Week 30 | 10.36 units on a scale | Standard Deviation 10.14 |
| TA-650 | PCDAI Score | Week 34 | 5.21 units on a scale | Standard Deviation 5.88 |
| TA-650 | PCDAI Score | Week 38 | 9.17 units on a scale | Standard Deviation 8.14 |
| TA-650 | PCDAI Score | Week 42 | 5.00 units on a scale | Standard Deviation 6.03 |
| TA-650 | PCDAI Score | Week 46 | 8.33 units on a scale | Standard Deviation 8.42 |
| TA-650 | PCDAI Score | Week 50 | 2.92 units on a scale | Standard Deviation 4.5 |
| TA-650 | PCDAI Score | Week 54 | 7.08 units on a scale | Standard Deviation 9.16 |
| TA-650 | PCDAI Score | The last time point | 10.18 units on a scale | Standard Deviation 12.03 |
Secondary
Percent of Patients Who Achieved PCDAI-Based Remission Rate.
Crohn's Disease Activity Index(PCDAI)-based remission was defined as a case where PCDAI on the evaluation day was decreased to not more than 10. Patients who satisfied the criterion for PCDAI response at least once in the evaluation at Week 2, 6 and 10 were defined as responders at Week 10. PCDAI was the sum (0 to 100) of the scores of 5 large categories. A larger PCDAI score represented higher disease activity. 5 large categories were as follows, i.e. history score (0 to 30), laboratory score (0 to 20), growth score (0 to 20), physical examination score (0 to 20) and extraintestinal manifestation score (0 to 10).
Time frame: Week 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54 and the last time point during the period from administration of the study drug to Week 54
Population: 2 patients were discontinued because of an adverse event and a lack of efficacy respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 2 | 42.9 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 6 | 78.6 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 10 | 71.4 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 14 | 85.7 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 18 | 85.7 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 22 | 71.4 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 26 | 78.6 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 30 | 64.3 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 34 | 83.3 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 38 | 75.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 42 | 83.3 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 46 | 75.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 50 | 91.7 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | Week 54 | 75.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved PCDAI-Based Remission Rate. | The last time point | 64.3 percentage of participants |
Secondary
Serum TA-650 Concentration
Median, Min and Max of serum TA-650 concentration at each evaluation point after dose of 5 mg/kg TA-650.
Time frame: After dose of Week 0 to 54 or at the timing of discontinuation. On the blood sampling day, before administration of the study drug. Week 0, 22 and 46, before administration and one hour after the administration. Week 14, 30 and 38, before administration.
Population: This table does not include the data after an increased dose of 10 mg/kg. In the case of missing examination values or the case where measurement was impossible due to problems with test samples, the relevant measurement result was treated as a missing value.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TA-650 | Serum TA-650 Concentration | Week 30, before dose | 3.75 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 34 | 11.55 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 0, before dose | 0.0 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 0, 1 hr after end of dose | 91.48 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 2, before dose | 17.47 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 6, before dose | 13.47 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 10 | 16.46 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 14, before dose | 4.54 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 18 | 14.80 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 22, before dose | 3.03 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 22, 1 hr after end of dose | 104.80 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 26 | 10.97 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 38, before dose | 2.04 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 42 | 9.48 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 46, before dose | 1.42 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 46, 1 hr after end of dose | 126.13 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 50 | 12.04 μg/mL |
| TA-650 | Serum TA-650 Concentration | Week 54 | 3.62 μg/mL |
Secondary
The Percent of the Patients Who Experienced an Adverse Event
Time frame: Until the last time point during the period from administration of the study drug to Week 54
Population: The analysis population is overall patients receiving at least one dose of TA-650 5 mg/kg or 10 mg/kg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TA-650 | The Percent of the Patients Who Experienced an Adverse Event | 100 percentage of participants |