Efficacy and Safety of Increased Dose of TA-650 (Infliximab) in Patients With Crohn's Disease (CD)

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00805766
• Collaborator: (none)
• Enrollment: 39
• Locations: 4
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Study to Assess the Efficacy and Safety of Increased Dose of TA-650 in Patients With Crohn's Disease (CD)
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: TA-650

Drug: TA-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.; Other Names: Infliximab

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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]

5. Antibody to TA-650 Determination [Screening Period (Week 0 to Week 16), Increased Dose Period (Week 0 to Week 40)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational site	Hokkaido		Japan
2	Investigational site	Kansai		Japan
3	Investigational site	Kanto		Japan
4	Investigational site	Kyushu		Japan

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Chair: Toshifumi Hibi, Professor, Department of Internal Medicine, Keio University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT00805766
• Other Study ID Numbers: TA-650-19
• First Posted: Dec 10, 2008
• Last Update Posted: Feb 9, 2018
• Last Verified: Jan 1, 2018

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

Study Results

Participant Flow

Arm/Group Title	TA-650
Arm/Group Description	Screening period: From the beginning of TA-650 5 mg/kg administration to the beginning of TA-650 10 mg/kg administration in the increased dose period in order to confirm that the effects of treatment with TA-650 5 mg/kg at 8-week intervals were insufficient. The screening period was to be up to 16 weeks. Patients who did not satisfy the dose-increasing criteria discontinued study treatment.Patients who discontinued study treatment during the screening period were to be evaluated until withdrawal. Increased dose period: From the beginning of administration of TA-650 10 mg/kg to evaluation at week 40. Patients who discontinued study treatment during the increased dose period were to be evaluated until withdrawal.
Period Title: Screening Period
STARTED	45
COMPLETED	39
NOT COMPLETED	6
Period Title: Screening Period
STARTED	39
COMPLETED	26
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	TA-650
Arm/Group Description
Overall Participants	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.5 (7.3)
Sex: Female, Male (Count of Participants)
Female	14 31.1%
Male	31 68.9%

Outcome Measures

1. Primary Outcome

Title	Median Crohn's Disease Activity Index (CDAI) Change From Week 0 to Week 8 in the Increased Dose Period
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TA-650
Arm/Group Description
Measure Participants	33
Median (95% Confidence Interval) [units on a scale]	95.0

2. Secondary Outcome

Title	CDAI at Each Evaluation Time Point in the Increased Dose Period
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	TA-650
Arm/Group Description
Measure Participants	38
Week 0	296.5
Week 4	119.0
Week 8	194.0
Week 12	126.0
Week 16	182.0
Week 20	121.0
Week 24	197.5
Week 28	105.0
Week 32	163.0
Week 36	141.0
Week 40	148.5
Week 40 (the last time point)	210.5

3. Secondary Outcome

Title	CDAI Remission Rates at Each Evaluation Time Point in the Increased Dose Period
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	TA-650
Arm/Group Description
Measure Participants	39
Week 4	59.5 132.2%
Week 8	39.4 87.6%
Week 12	70.0 155.6%
Week 16	31.0 68.9%
Week 20	58.6 130.2%
Week 24	28.6 63.6%
Week 28	60.7 134.9%
Week 32	37.0 82.2%
Week 36	59.3 131.8%
Week 40	50.0 111.1%
Week 40 (the last time point)	41.0 91.1%

4. Secondary Outcome

Title	CDAI Change at Each Evaluation Time Point in the Increased Dose Period
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	TA-650
Arm/Group Description
Measure Participants	38
Week 0 to Week 4	163.0
Week 0 to Week 8	95.0
Week 0 to Week 12	161.0
Week 0 to Week 16	95.0
Week 0 to Week 20	164.0
Week 0 to Week 24	100.0
Week 0 to Week 28	156.5
Week 0 to Week 32	110.0
Week 0 to Week 36	139.0
Week 0 to Week 40	95.0
Week 0 to 40(last measurable time point)	87.0

5. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TA-650
Arm/Group Description
Measure Participants	39
Screening Period (SP), Week 0 (pre-dose)	1.12
SP, 1 hr after treatment end for week 0	97.74
SP, Week 4	4.93
SP, Week 8	0.30
SP, Week 12	5.25
SP, Week 16	0.79
Increased dose Period(IP), Week0 (pre-dose)	0.30
IP, 1 hr after treatment end for week 0	191.24
IP, Week 4	9.93
IP, Week 8	1.29
IP, Week 12	11.20
IP, Week 16 (pre-dose)	1.31
IP, 1hr after administration at week 16	203.16
IP, Week 20	8.71
IP, Week 24	1.83
IP, Week 28	9.97
IP, Week 32	1.60
IP, Week 36	12.72
IP, Week 40	2.18

6. Secondary Outcome

Title	Antibody to TA-650 Determination
Time Frame	Screening Period (Week 0 to Week 16), Increased Dose Period (Week 0 to Week 40)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Screening Period	Increased Dose Period
Arm/Group Description
Measure Participants	39	39
Negative	23.1 51.3%	17.9 NaN
Positive	5.1 11.3%	5.1 NaN
Inconclusive	71.8 159.6%	76.9 NaN

Adverse Events

Arm/Group Title	Entire Evaluation Period		Screening Period		Increased Dose Period
Arm/Group Description	Screening Period + Increased Dose Period
All Cause Mortality
	Entire Evaluation Period		Screening Period		Increased Dose Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Entire Evaluation Period		Screening Period		Increased Dose Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/45 (20%)		2/45 (4.4%)		8/39 (20.5%)
Gastrointestinal disorders
Crohn's disease	6/45 (13.3%)		1/45 (2.2%)		5/39 (12.8%)
Melaena	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Peritonitis	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Infections and infestations
Bronchitis	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Cytomegalovirus infection	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Injury, poisoning and procedural complications
Upper limb fracture	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Nervous system disorders
Chronic inflammatory demyelinating polyradiculoneuropathy	1/45 (2.2%)		1/45 (2.2%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Entire Evaluation Period		Screening Period		Increased Dose Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/45 (82.2%)		25/45 (55.6%)		29/39 (74.4%)
Blood and lymphatic system disorders
Anaemia	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Iron deficiency anaemia	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Gastrointestinal disorders
Periodontitis	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
General disorders
Pyrexia	2/45 (4.4%)		1/45 (2.2%)		1/39 (2.6%)
Oedema peripheral	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Infections and infestations
Nasopharyngitis	12/45 (26.7%)		3/45 (6.7%)		11/39 (28.2%)
Influenza	3/45 (6.7%)		1/45 (2.2%)		2/39 (5.1%)
Gastroenteritis	2/45 (4.4%)		0/45 (0%)		2/39 (5.1%)
Pharyngitis	2/45 (4.4%)		0/45 (0%)		2/39 (5.1%)
Bronchitis	1/45 (2.2%)		1/45 (2.2%)		0/39 (0%)
Folliculitis	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Otitis externa	1/45 (2.2%)		1/45 (2.2%)		0/39 (0%)
Otitis media	1/45 (2.2%)		1/45 (2.2%)		0/39 (0%)
Vulvovaginal candidiasis	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Anal fistula infection	1/45 (2.2%)		1/45 (2.2%)		0/39 (0%)
Injury, poisoning and procedural complications
Injury	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Contusion	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Investigations
DNA antibody positive	18/45 (40%)		15/45 (33.3%)		4/39 (10.3%)
Blood urine present	2/45 (4.4%)		2/45 (4.4%)		1/39 (2.6%)
Liver function test abnormal	2/45 (4.4%)		0/45 (0%)		2/39 (5.1%)
Protein urine present	2/45 (4.4%)		2/45 (4.4%)		0/39 (0%)
Blood alkaline phosphatase increased	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Chest X-ray abnormal	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/45 (2.2%)		1/45 (2.2%)		1/39 (2.6%)
Musculoskeletal stiffness	1/45 (2.2%)		1/45 (2.2%)		1/39 (2.6%)
Musculoskeletal pain	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Nervous system disorders
Headache	3/45 (6.7%)		2/45 (4.4%)		2/39 (5.1%)
Dizziness	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Somnolence	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Renal and urinary disorders
Renal mass	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Reproductive system and breast disorders
Haematospermia	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	5/45 (11.1%)		2/45 (4.4%)		3/39 (7.7%)
Dyspnoea	2/45 (4.4%)		1/45 (2.2%)		1/39 (2.6%)
Upper respiratory tract inflammation	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Cough	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Epistaxis	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Rhinitis allergic	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Skin and subcutaneous tissue disorders
Eczema	3/45 (6.7%)		2/45 (4.4%)		1/39 (2.6%)
Acne	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Alopecia	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Polymorphic light eruption	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Pruritus	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)
Vascular disorders
Hot flush	1/45 (2.2%)		0/45 (0%)		1/39 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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