Clinical Study of TA-650 in Pediatric Patients With Crohn's Disease

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01580670
• Collaborator: (none)
• Enrollment: 14
• Locations: 7
• Arm: 1
• Duration (Months): 36
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pediatric Crohn's Disease	Drug: TA-650	Phase 3

Detailed Description

This is an open-label, uncontrolled, multicenter Phase 3 study conducted in Japan.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of TA-650 in Pediatric Patients With Moderate to Severe Crohn's Disease
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: TA-650 Responder criteria: Case where PCDAI score on the evaluation day was decreased by at least 15 points from that in the screening period and was ≤30. Criteria for dose-increasing: When either of the following 2 items was satisfied after Week 14, the relevant patient would be considered to satisfy the criteria for dose increasing to 10 mg/kg. PCDAI score on the evaluation day was increased by at least 15 points compared to the lowest PCDAI score observed at Week 2, 6 or 10 PCDAI score on the evaluation day exceeds 30

Drug: TA-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.; Other Names: Infliximab

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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).

3. 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).

4. 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.

5. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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.).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational site	Chubu		Japan
2	Investigational site	Hokkaido		Japan
3	Investigational site	Hokuriku		Japan
4	Investigational site	Kanto		Japan
5	Investigational site	Kinki		Japan
6	Investigational site	Kyusyu		Japan
7	Investigational site	Tohoku		Japan

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Director: Toshifumi Hibi, MD, Kitasato University Kitasato Institute Hospital
• Study Director: Kazuoki Kondo, MD, Mitsubihsi Tanabe Pharma Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT01580670
• Other Study ID Numbers: TA-650-20
• First Posted: Apr 19, 2012
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Mitsubishi Tanabe Pharma Corporation: Infliximab; REMICADE; TA-650; pediatric Crohn's disease
• Additional relevant MeSH terms: Crohn Disease; Infliximab

Study Results

Participant Flow

Arm/Group Title	TA-650
Arm/Group Description	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.
Period Title: Induction Period (Week 0 to 14)
STARTED	14
COMPLETED	14
NOT COMPLETED	0
Period Title: Induction Period (Week 0 to 14)
STARTED	14
COMPLETED	12
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	TA-650
Arm/Group Description	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.
Overall Participants	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.5 (1.9)
Sex: Female, Male (Count of Participants)
Female	3 21.4%
Male	11 78.6%

Outcome Measures

1. Primary Outcome

Title	Percent of Patients Who Achieved PCDAI Response
Description	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

Outcome Measure Data

Analysis Population Description

2 patients were discontinued because of an adverse event and a lack of efficacy respectively.

Arm/Group Title	TA-650
Arm/Group Description	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.
Measure Participants	14
Week 2	78.6 561.4%
Week 6	100.0 714.3%
Week 10	100.0 714.3%
Week 14	92.9 663.6%
Week 18	100.0 714.3%
Week 22	92.9 663.6%
Week 26	100.0 714.3%
Week 30	92.9 663.6%
Week 34	100.0 714.3%
Week 38	91.7 655%
Week 42	100.0 714.3%
Week 46	91.7 655%
Week 50	100.0 714.3%
Week 54	91.7 655%
The last time point	85.7 612.1%

2. Secondary Outcome

Title	PCDAI Score
Description	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

Outcome Measure Data

Analysis Population Description

2 patients were discontinued because of an adverse event and a lack of efficacy respectively.

Arm/Group Title	TA-650
Arm/Group Description	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.
Measure Participants	14
Week 0	36.43 (4.78)
Week 2	15.71 (9.63)
Week 6	8.75 (6.56)
Week 10	6.43 (5.86)
Week 14	7.86 (8.82)
Week 18	5.36 (5.87)
Week 22	9.11 (10.68)
Week 26	6.25 (6.63)
Week 30	10.36 (10.14)
Week 34	5.21 (5.88)
Week 38	9.17 (8.14)
Week 42	5.00 (6.03)
Week 46	8.33 (8.42)
Week 50	2.92 (4.50)
Week 54	7.08 (9.16)
The last time point	10.18 (12.03)

3. Secondary Outcome

Title	Change From Baseline of PCDAI Score
Description	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

Outcome Measure Data

Analysis Population Description

2 patients were discontinued because of an adverse event and a lack of efficacy respectively.

Arm/Group Title	TA-650
Arm/Group Description	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.
Measure Participants	14
Week 2	-20.71 (8.57)
Week 6	-27.68 (6.24)
Week 10	-30.00 (6.35)
Week 14	-28.57 (7.05)
Week 18	-31.07 (6.63)
Week 22	-27.32 (9.01)
Week 26	-30.18 (7.37)
Week 30	-26.07 (8.86)
Week 34	-30.21 (7.11)
Week 38	-26.25 (10.03)
Week 42	-30.42 (7.37)
Week 46	-27.08 (9.99)
Week 50	-32.50 (5.84)
Week 54	-28.33 (10.08)
The last time point	-26.25 (10.69)

4. Secondary Outcome

Title	Percent of Patients Who Achieved PCDAI-Based Remission Rate.
Description	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

Outcome Measure Data

Analysis Population Description

2 patients were discontinued because of an adverse event and a lack of efficacy respectively.

Arm/Group Title	TA-650
Arm/Group Description	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.
Measure Participants	14
Week 2	42.9 306.4%
Week 6	78.6 561.4%
Week 10	71.4 510%
Week 14	85.7 612.1%
Week 18	85.7 612.1%
Week 22	71.4 510%
Week 26	78.6 561.4%
Week 30	64.3 459.3%
Week 34	83.3 595%
Week 38	75.0 535.7%
Week 42	83.3 595%
Week 46	75.0 535.7%
Week 50	91.7 655%
Week 54	75.0 535.7%
The last time point	64.3 459.3%

5. Secondary Outcome

Title	Serum TA-650 Concentration
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	TA-650
Arm/Group Description	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.
Measure Participants	14
Week 0, before dose	0.0
Week 0, 1 hr after end of dose	91.48
Week 2, before dose	17.47
Week 6, before dose	13.47
Week 10	16.46
Week 14, before dose	4.54
Week 18	14.80
Week 22, before dose	3.03
Week 22, 1 hr after end of dose	104.80
Week 26	10.97
Week 30, before dose	3.75
Week 34	11.55
Week 38, before dose	2.04
Week 42	9.48
Week 46, before dose	1.42
Week 46, 1 hr after end of dose	126.13
Week 50	12.04
Week 54	3.62

6. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The analysis population is overall patients receiving at least one dose of TA-650 5 mg/kg or 10 mg/kg.

Arm/Group Title	TA-650
Arm/Group Description	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.
Measure Participants	14
Number [percentage of participants]	100 714.3%

Adverse Events

Arm/Group Title	TA-650
Arm/Group Description	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.
All Cause Mortality
	TA-650
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TA-650
	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)
Gastrointestinal disorders
Crohn's disease	1/14 (7.1%)
Small intestinal obstruction	1/14 (7.1%)
Other (Not Including Serious) Adverse Events
	TA-650
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/14 (7.1%)
Cardiac disorders
Atrioventricular dissociation	1/14 (7.1%)
Eye disorders
Blepharitis	1/14 (7.1%)
Conjunctivitis allergic	1/14 (7.1%)
Eyelid oedema	1/14 (7.1%)
Gastrointestinal disorders
Constipation	1/14 (7.1%)
Nausea	1/14 (7.1%)
Stomatitis	1/14 (7.1%)
General disorders
Peripheral swelling	1/14 (7.1%)
Hepatobiliary disorders
Hepatic steatosis	1/14 (7.1%)
Infections and infestations
Acute sinusitis	1/14 (7.1%)
Enteritis infectious	1/14 (7.1%)
Folliculitis	1/14 (7.1%)
Gastroenteritis	3/14 (21.4%)
Impetigo	1/14 (7.1%)
Influenza	2/14 (14.3%)
Nasopharyngitis	3/14 (21.4%)
Skin infection	1/14 (7.1%)
Upper respiratory tract infection	2/14 (14.3%)
Viral infection	1/14 (7.1%)
Injury, poisoning and procedural complications
Arthropod sting	1/14 (7.1%)
Investigations
Amylase increased	1/14 (7.1%)
Antinuclear antibody increased	1/14 (7.1%)
Double stranded DNA antibody positive	7/14 (50%)
Weight increased	1/14 (7.1%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/14 (7.1%)
Nervous system disorders
Dizziness	1/14 (7.1%)
Headache	3/14 (21.4%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	1/14 (7.1%)
Skin and subcutaneous tissue disorders
Acne	1/14 (7.1%)
Dermatitis atopic	1/14 (7.1%)
Dermatitis contact	1/14 (7.1%)
Eczema	2/14 (14.3%)
Eczema asteatotic	1/14 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.