Pediatric Ulcerative Colitis
Conditions
Keywords
Infliximab, REMICADE, TA-650
Brief summary
The purpose of this study is to evaluate the the efficacy of TA-650 using Clinical activity index (CAI) score and other evaluation indicators in pediatric patients with moderate to severe ulcerative colitis after TA-650 administration of at a dose of 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks at weeks 14 and 22. The safety and pharmacokinetics are also evaluated.
Interventions
DRUGTA-650
TA-650 will be intravenously infused at 5 mg/kg as an induction regimen at Weeks 0, 2, 6. For subjects who meet the responder criteria, TA-650 will be administered at 8-week intervals thereafter until week 22.
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 ulcerative colitis at least 3 months prior to screening. * Have active ulcerative colitis despite adequate conventional therapy.
Exclusion criteria
* Patients who have severe pancolitis. * Patients who have undergone surgery for ulcerative colitis within 8 weeks before enrollment or who were judged to require surgery for ulcerative colitis at enrollment. * Patients who have a history of treatment with infliximab or other biologic products (anti-TNFα agents, anti-IL-6 agents, etc.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Who Achieved CAI Remission | Weeks 2, 6, 8, 10, 14, 18, 22, 26, 30, and the last time point during the period from administration of the study drug to Week 30 | Clinical activity index (CAI) remission was defined as a case where a CAI score was not more than 4 on the evaluation day. CAI score was an activity index to evaluate disease activity, which is calculated as the sum (0 to 29 points) of subscores for 7 clinical conditions, consisting of the number of stools per week, blood in stools (based on weekly average), investigator's global assessment of the symptomatic state, abdominal pain/cramps, temperature elevation due to ulcerative colitis, extraintestinal manifestations, and laboratory findings (hemoglobin or ESR). A higher score indicates greater disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAI Score | Baseline,Weeks 2, 6, 8, 10, 14, 18, 22, 26, 30, and the last time point during the period from administration of the study drug to Week 30 | CAI score was an activity index to evaluate disease activity, which is calculated as the sum (0 to 29 points) of subscores for 7 clinical conditions, consisting of the number of stools per week, blood in stools (based on weekly average), investigator's global assessment of the symptomatic state, abdominal pain/cramps, temperature elevation due to ulcerative colitis, extraintestinal manifestations, and laboratory findings (hemoglobin or ESR). A higher score indicates greater disease activity. |
| Partial Mayo Score | Baseline,Weeks 2, 6, 8, 10, 14, 18, 22, 26, 30, and the last time point during the period from administration of the study drug to Week 30 | Mayo score consists of four subscores (stool frequency, rectal bleeding, physician's global assessment and findings of endoscopy), each of which was assessed according to a four-level rating scale (0 to 3 points), and was determined from a total of the four subscores (0 to 12 points). In addition, the sum of the subscores (0 to 9 points) for stool frequency, rectal bleeding and physician's global assessment was used as a partial Mayo score. A higher score indicates greater disease activity. |
| Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Baseline,Weeks 2, 6, 8, 10, 14, 18, 22, 26, 30, and the last time point during the period from administration of the study drug to Week 30 | PUCAI score was determined as a total of the subscores for each of the six evaluation items (0 to 85), including abdominal pain, rectal bleeding, stool consistency of most stools, number of stools per 24 hours, nocturnal stools and activity level. A higher score indicates greater disease activity. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TA-650 TA-650 is administered at a dose of 5 mg/kg at Weeks 0, 2 and 6, followed by administration at 8-week intervals at Weeks 14 and 22, based on the evaluation index such as CAI score. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Worsening ulcerative colitis | 2 |
Baseline characteristics
| Characteristic | TA-650 |
|---|---|
| Age, Continuous | 13.7 years STANDARD_DEVIATION 2.1 |
| Sex: Female, Male Female | 10 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 | 19 / 21 |
| serious Total, serious adverse events | 3 / 21 |
Outcome results
Primary
Percent of Patients Who Achieved CAI Remission
Clinical activity index (CAI) remission was defined as a case where a CAI score was not more than 4 on the evaluation day. CAI score was an activity index to evaluate disease activity, which is calculated as the sum (0 to 29 points) of subscores for 7 clinical conditions, consisting of the number of stools per week, blood in stools (based on weekly average), investigator's global assessment of the symptomatic state, abdominal pain/cramps, temperature elevation due to ulcerative colitis, extraintestinal manifestations, and laboratory findings (hemoglobin or ESR). A higher score indicates greater disease activity.
Time frame: Weeks 2, 6, 8, 10, 14, 18, 22, 26, 30, and the last time point during the period from administration of the study drug to Week 30
Population: Five patients were discontinued. The reasons for discontinuation were adverse event in 1 patient, lack of efficacy in 2 patients, and worsening ulcerative colitis in 2 patients. Two non-responders were observed, and both of them completed the efficacy evaluation at Week 8.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 2 | 60.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 6 | 80.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 8 | 80.0 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 10 | 77.8 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 14 | 87.5 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 18 | 87.5 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 22 | 64.3 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 26 | 85.7 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | Weeks 30 | 64.3 percentage of participants |
| TA-650 | Percent of Patients Who Achieved CAI Remission | The last time point | 42.9 percentage of participants |
Secondary
CAI Score
CAI score was an activity index to evaluate disease activity, which is calculated as the sum (0 to 29 points) of subscores for 7 clinical conditions, consisting of the number of stools per week, blood in stools (based on weekly average), investigator's global assessment of the symptomatic state, abdominal pain/cramps, temperature elevation due to ulcerative colitis, extraintestinal manifestations, and laboratory findings (hemoglobin or ESR). A higher score indicates greater disease activity.
Time frame: Baseline,Weeks 2, 6, 8, 10, 14, 18, 22, 26, 30, and the last time point during the period from administration of the study drug to Week 30
Population: Five patients were discontinued. The reasons for discontinuation were adverse event in 1 patient, lack of efficacy in 2 patients, and worsening ulcerative colitis in 2 patients. Two non-responders were observed, and both of them completed the efficacy evaluation at Week 8.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TA-650 | CAI Score | The last time point | 5.6 units on a scale | Standard Deviation 3.8 |
| TA-650 | CAI Score | Baseline | 9.7 units on a scale | Standard Deviation 2.7 |
| TA-650 | CAI Score | Weeks 2 | 4.0 units on a scale | Standard Deviation 3.2 |
| TA-650 | CAI Score | Weeks 6 | 3.5 units on a scale | Standard Deviation 3.5 |
| TA-650 | CAI Score | Weeks 8 | 3.2 units on a scale | Standard Deviation 3.5 |
| TA-650 | CAI Score | Weeks 10 | 2.7 units on a scale | Standard Deviation 2.9 |
| TA-650 | CAI Score | Weeks 14 | 2.7 units on a scale | Standard Deviation 3 |
| TA-650 | CAI Score | Weeks 18 | 2.6 units on a scale | Standard Deviation 2.6 |
| TA-650 | CAI Score | Weeks 22 | 3.3 units on a scale | Standard Deviation 3.1 |
| TA-650 | CAI Score | Weeks 26 | 2.5 units on a scale | Standard Deviation 2.3 |
| TA-650 | CAI Score | Weeks 30 | 3.5 units on a scale | Standard Deviation 2.2 |
Secondary
Partial Mayo Score
Mayo score consists of four subscores (stool frequency, rectal bleeding, physician's global assessment and findings of endoscopy), each of which was assessed according to a four-level rating scale (0 to 3 points), and was determined from a total of the four subscores (0 to 12 points). In addition, the sum of the subscores (0 to 9 points) for stool frequency, rectal bleeding and physician's global assessment was used as a partial Mayo score. A higher score indicates greater disease activity.
Time frame: Baseline,Weeks 2, 6, 8, 10, 14, 18, 22, 26, 30, and the last time point during the period from administration of the study drug to Week 30
Population: Five patients were discontinued. The reasons for discontinuation were adverse event in 1 patient, lack of efficacy in 2 patients, and worsening ulcerative colitis in 2 patients. Two non-responders were observed, and both of them completed the efficacy evaluation at Week 8.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TA-650 | Partial Mayo Score | Baseline | 5.6 units on a scale | Standard Deviation 1.6 |
| TA-650 | Partial Mayo Score | Weeks 2 | 2.6 units on a scale | Standard Deviation 2.3 |
| TA-650 | Partial Mayo Score | Weeks 6 | 2.2 units on a scale | Standard Deviation 2 |
| TA-650 | Partial Mayo Score | Weeks 8 | 1.7 units on a scale | Standard Deviation 1.7 |
| TA-650 | Partial Mayo Score | Weeks 10 | 2.2 units on a scale | Standard Deviation 2.1 |
| TA-650 | Partial Mayo Score | Weeks 14 | 1.9 units on a scale | Standard Deviation 1.9 |
| TA-650 | Partial Mayo Score | Weeks 18 | 2.1 units on a scale | Standard Deviation 1.8 |
| TA-650 | Partial Mayo Score | Weeks 22 | 2.4 units on a scale | Standard Deviation 2.1 |
| TA-650 | Partial Mayo Score | Weeks 26 | 1.8 units on a scale | Standard Deviation 1.7 |
| TA-650 | Partial Mayo Score | Weeks 30 | 2.8 units on a scale | Standard Deviation 1.9 |
| TA-650 | Partial Mayo Score | The last time point | 3.7 units on a scale | Standard Deviation 2.2 |
Secondary
Pediatric Ulcerative Colitis Activity Index (PUCAI) Score
PUCAI score was determined as a total of the subscores for each of the six evaluation items (0 to 85), including abdominal pain, rectal bleeding, stool consistency of most stools, number of stools per 24 hours, nocturnal stools and activity level. A higher score indicates greater disease activity.
Time frame: Baseline,Weeks 2, 6, 8, 10, 14, 18, 22, 26, 30, and the last time point during the period from administration of the study drug to Week 30
Population: Five patients were discontinued. The reasons for discontinuation were adverse event in 1 patient, lack of efficacy in 2 patients, and worsening ulcerative colitis in 2 patients. Two non-responders were observed, and both of them completed the efficacy evaluation at Week 8.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Baseline | 47.1 units on a scale | Standard Deviation 15.2 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 2 | 20.3 units on a scale | Standard Deviation 16.3 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 6 | 17.3 units on a scale | Standard Deviation 17.5 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 8 | 12.5 units on a scale | Standard Deviation 13.5 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 10 | 14.7 units on a scale | Standard Deviation 16.9 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 14 | 12.2 units on a scale | Standard Deviation 12 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 18 | 14.4 units on a scale | Standard Deviation 16.8 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 22 | 18.2 units on a scale | Standard Deviation 15.6 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 26 | 13.2 units on a scale | Standard Deviation 14 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | Weeks 30 | 19.3 units on a scale | Standard Deviation 18.8 |
| TA-650 | Pediatric Ulcerative Colitis Activity Index (PUCAI) Score | The last time point | 28.8 units on a scale | Standard Deviation 22.5 |