A Safety and Effectiveness Study of Golimumab in Japanese Patients With Moderately to Severely Active Ulcerative Colitis.

• Sponsor: Janssen Pharmaceutical K.K. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01863771
• Collaborator: (none)
• Enrollment: 144
• Locations: 38
• Arms: 2
• Actual Duration (Months): 34.5
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate safety and effectiveness of golimumab in Japanese participants with moderately to severely active ulcerative colitis.

Condition or Disease	Intervention/Treatment	Phase
Colitis, Ulcerative	Drug: Golimumab; Other: Placebo	Phase 3

Detailed Description

This is a double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (study in which an inactive substance is given to one group of participants, while the study medication is given to another group), multicenter (study conducted at multiple sites), 2-arm (two groups), parallel-group (each group of participants will be treated at the same time), randomized-withdrawal (participants receiving study medication for a specified time will be later randomized to receive either study medication or placebo.) study, including an open-label (all people know the identity of the intervention) induction phase. Approximately 200 participants will participate in this study. This study will consist of an induction phase, a maintenance phase, and a follow-up phase. During the induction phase (lasting 6 weeks) participants will receive 200 mg subcutaneous (SC) (under the skin) golimumab at Week 0 and 100 mg SC golimumab at Week 2. During the maintenance phase (up to Week 52) all participants who show a clinical response (measure of therapeutic effect of study medication) to golimumab during the induction phase will be randomly allocated in a 1:1 ratio to receive either SC administration of placebo (Group 1) or 100 mg golimumab (Group 2) every 4 weeks from Week 0 to Week 52. Participants who do not show clinical response to golimumab will also receive 100 mg SC administration of golimumab until Week 4 and if, by Week 8 of the maintenance phase, these participant's disease activity does not appear to be improving, participants will be discontinued from further study medication administration and will be followed up for safety evaluations 16 weeks after the last administration of study medication. However, if disease activity of these participants improves at Week 8, they will continue to receive golimumab (100 mg every 4 weeks) through Week 52 of the maintenance phase. The follow-up phase will be of 16 weeks duration. During this study, any participant who have a clinical response during the induction phase but lose clinical response at any time will be eligible for dose adjustment only once as follows: 1) participants receiving placebo (Group 1) will receive golimumab 100 mg; 2) participants receiving golimumab 100 mg (Group 2) will continue to receive golimumab 100 mg. Safety evaluations will include assessment of adverse events, laboratory measurements, antinuclear antibodies/anti-double-stranded deoxyribonucleic acid antibodies, and vital signs. The maximum study duration for a participant will be 68 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Multicenter, Placebo-controlled, Double-blind, Randomized-withdrawal Study to Evaluate the Safety and Efficacy of Golimumab Maintenance Therapy, Administered Subcutaneously, in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
• Actual Study Start Date: Mar 15, 2013
• Actual Primary Completion Date: Jan 29, 2016
• Actual Study Completion Date: Jan 29, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Golimumab	Drug: Golimumab; Participants will receive 200 mg golimumab at Week 0 and 100 mg golimumab at Week 2 as a subcutaneous (SC) (under the skin) injection in the induction phase. Participants who have a clinical response in the induction phase and are randomly allocated to golimumab in the maintenance phase will receive 100 mg SC every 4 weeks through Week 52. Participants who do not have a clinical response in the induction phase will receive 100 mg of golimumab SC at Week 4 and will continue with 100 mg of golimumab SC every 4 weeks through Week 52 only if a response is obtained by Week 8.
Placebo Comparator: Placebo	Other: Placebo; Participants who have a clinical response to golimumab in the induction phase and are randomly allocated to placebo in the maintenance phase will receive SC placebo every 4 weeks through Week 52. However, participants receiving placebo and who will lose clinical response any time during the study will be eligible to receive 100 mg golimumab SC every 4 weeks through Week 52.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved Clinical Response Through Maintenance-Week 54 Measured Using the Mayo Score [Up to Week 54]

   Clinical response was defined as a decrease from Induction-Week 0 in the Mayo score by greater than or equal to (>=) 30 percent and >=3 points, with a decrease in the rectal bleeding subscore of >= 1 or a rectal bleeding subscore of 0 or 1. The Mayo score is the primary tool for assessing ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, findings of endoscopy, and physician's global assessment) which range from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease.

Secondary Outcome Measures

1. Number of Participants Who Achieved Clinical Remission at Both Maintenance-Week 30 and Week 54 [Weeks 30 and 54]

   Clinical remission (as measured by the Mayo score) was defined as a Mayo score of less than or equal to (<=) 2 points, with no individual sub-score greater than (>) 1.

2. Number of Participants With Mucosal Healing at Both Maintenance-Week 30 and Week 54 [Weeks 30 and 54]

   Mucosal healing is defined as an endoscopy subscore of 0 or 1, where 0 indicates normal or inactive disease and 1 indicates mild disease (erythema, decreased vascular pattern, mild friability). Endoscopy subscore is one of the 4 subscores of the Mayo score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with ulcerative colitis diagnosed prior to screening

• Participants should have current treatment for ulcerative colitis with at least one of the following therapies: oral 5-aminosalicylates (5-ASAs), oral corticosteroids, 6-mercaptopurine (6-MP), or azathioprine (AZA)

• Participants must have a history of failure to respond to, or tolerate, at least 1 of the following therapies: oral 5-ASAs, oral corticosteroids, 6-MP, or AZA

• Participants must be ambulatory and have moderately to severely active ulcerative colitis confirmed during the screening sigmoidoscopy by a greater than or equal to 2 using the endoscopy subscore of the Mayo score

• Participants must have moderately to severely active ulcerative colitis, defined as a baseline Mayo score of 6 to 12, inclusive

Exclusion Criteria:

• Participants with ulcerative colitis limited to the rectum only or to less than 20 cm of the colon

• Participants with stoma

• Participants with fistula or history of fistula

• Participants who require, or required within the 2 months prior to screening, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from study agent treatment

• Participants with symptomatic colonic or small bowel obstruction, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Abiko		Japan
2		Chiba		Japan
3		Chikushinoshi		Japan
4		Fujiidera		Japan
5		Fukuoka		Japan
6		Fushimi		Japan
7		Hamamatsu		Japan
8		Hirosaki		Japan
9		Hiroshima		Japan
10		Ikeda		Japan
11		Izumiotsu		Japan
12		Izumo		Japan
13		Kagoshima		Japan
14		Kahoku		Japan
15		Kanazawa		Japan
16		Kochi		Japan
17		Kurume		Japan
18		Maebashi		Japan
19		Miyazaki		Japan
20		Nagasaki		Japan
21		Nagoya		Japan
22		Nishinomiya		Japan
23		Oita		Japan
24		Osaka		Japan
25		Saga		Japan
26		Sakura		Japan
27		Sapporo		Japan
28		Sendai		Japan
29		Suita		Japan
30		Sunto		Japan
31		Tokushima		Japan
32		Tokyo		Japan
33		Toyota		Japan
34		Tsukuba		Japan
35		Tsu		Japan
36		Wakayama		Japan
37		Yokkaichi		Japan
38		Yokohama		Japan

Sponsors and Collaborators

• Janssen Pharmaceutical K.K.

Investigators

• Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Pharmaceutical K.K.
• ClinicalTrials.gov Identifier: NCT01863771
• Other Study ID Numbers: CR100937; CNTO148UCO3001
• First Posted: May 29, 2013
• Last Update Posted: Apr 5, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Janssen Pharmaceutical K.K.: Ulcerative Colitis; Japanese; Subcutaneous; Golimumab
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Golimumab

Study Results

Participant Flow

Arm/Group Title	Group1: Golimumab [Induction]	Group 2: Golimumab 100 mg [Maintenance]	Group 3: Placebo [Maintenance]	Group 4: Golimumab 100 mg [Maintenance]
Arm/Group Description	Participants received golimumab 200 milligram (mg) once at Week 0 and golimumab 100 mg once at Week 2 subcutaneously (SC).	Participants who responded to golimumab induction treatment received golimumab 100 mg SC every 4 weeks (q4w) through Week 52.	Participants who responded to golimumab induction treatment received placebo SC every 4 weeks (q4w) through Week 52.	Participants who not responded to golimumab induction dosing received golimumab 100 mg SC once at Week 0 and once at Week 4, and based on clinical response every 4 weeks through Week 52.
Period Title: Induction Phase
STARTED	144	0	0	0
COMPLETED	123	0	0	0
NOT COMPLETED	21	0	0	0
Period Title: Induction Phase
STARTED	0	32	31	60
COMPLETED	0	27	19	17
NOT COMPLETED	0	5	12	43

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants who received golimumab 200 milligram (mg) once at Week 0 and golimumab 100 mg once at Week 2 subcutaneously (SC) in the induction phase.
Overall Participants	144
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.4 (14.74)
Sex: Female, Male (Count of Participants)
Female	46 31.9%
Male	98 68.1%
Region of Enrollment (Count of Participants)
Japan	144 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieved Clinical Response Through Maintenance-Week 54 Measured Using the Mayo Score
Description	Clinical response was defined as a decrease from Induction-Week 0 in the Mayo score by greater than or equal to (>=) 30 percent and >=3 points, with a decrease in the rectal bleeding subscore of >= 1 or a rectal bleeding subscore of 0 or 1. The Mayo score is the primary tool for assessing ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, findings of endoscopy, and physician's global assessment) which range from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease.
Time Frame	Up to Week 54

Outcome Measure Data

Analysis Population Description

Efficacy full analysis set for maintenance phase included all participants who responded to golimumab induction treatment and subsequently randomized at Week 0 in maintenance phase. Data for this outcome was not planned to be analyzed for participants who had not responded to golimumab induction dosing, as pre-specified in protocol.

Arm/Group Title	Placebo	Golimumab
Arm/Group Description	Participants who responded to golimumab induction treatment received placebo subcutaneously (SC) every 4 weeks (q4w) through Week 52 in the maintenance phase.	Participants received golimumab 200 mg (once at Week 0) and golimumab 100 mg (once at Week 2) SC in induction phase. Participants who responded to golimumab induction treatment received golimumab 100 mg SC, q4w through Week 52 and participants who not responded to golimumab induction treatment received golimumab 100 mg SC at Weeks 0 and 4, and based on clinical response every 4 weeks through Week 52 in maintenance phase.
Measure Participants	31	32
Number [participants]	6 4.2%	18 NaN

2. Secondary Outcome

Title	Number of Participants Who Achieved Clinical Remission at Both Maintenance-Week 30 and Week 54
Description	Clinical remission (as measured by the Mayo score) was defined as a Mayo score of less than or equal to (<=) 2 points, with no individual sub-score greater than (>) 1.
Time Frame	Weeks 30 and 54

Outcome Measure Data

Analysis Population Description

Efficacy full analysis set for maintenance phase included all participants who responded to golimumab induction treatment and subsequently randomized at Week 0 in maintenance phase. Data for this outcome was not planned to be analyzed for participants who had not responded to golimumab induction dosing, as pre-specified in protocol.

Arm/Group Title	Placebo	Golimumab
Arm/Group Description	Participants who responded to golimumab induction treatment received placebo subcutaneously (SC) every 4 weeks (q4w) through Week 52 in the maintenance phase.	Participants received golimumab 200 mg (once at Week 0) and golimumab 100 mg (once at Week 2) SC in induction phase. Participants who responded to golimumab induction treatment received golimumab 100 mg SC, q4w through Week 52 and participants who not responded to golimumab induction treatment received golimumab 100 mg SC at Weeks 0 and 4, and based on clinical response every 4 weeks through Week 52 in maintenance phase.
Measure Participants	31	32
Number [participants]	2 1.4%	16 NaN

3. Secondary Outcome

Title	Number of Participants With Mucosal Healing at Both Maintenance-Week 30 and Week 54
Description	Mucosal healing is defined as an endoscopy subscore of 0 or 1, where 0 indicates normal or inactive disease and 1 indicates mild disease (erythema, decreased vascular pattern, mild friability). Endoscopy subscore is one of the 4 subscores of the Mayo score.
Time Frame	Weeks 30 and 54

Outcome Measure Data

Analysis Population Description

Efficacy full analysis set for maintenance phase included all participants who responded to golimumab induction treatment and subsequently randomized at Week 0 in maintenance phase. Data for this outcome was not planned to be analyzed for participants who had not responded to golimumab induction dosing, as pre-specified in protocol.

Arm/Group Title	Placebo	Golimumab
Arm/Group Description	Participants who responded to golimumab induction treatment received placebo subcutaneously (SC) every 4 weeks (q4w) through Week 52 in the maintenance phase.	Participants received golimumab 200 mg (once at Week 0) and golimumab 100 mg (once at Week 2) SC in induction phase. Participants who responded to golimumab induction treatment received golimumab 100 mg SC, q4w through Week 52 and participants who not responded to golimumab induction treatment received golimumab 100 mg SC at Weeks 0 and 4, and based on clinical response every 4 weeks through Week 52 in maintenance phase.
Measure Participants	31	32
Number [participants]	5 3.5%	19 NaN

Adverse Events

Adverse Event Reporting Description	Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Arm/Group Title	Group1: Golimumab [Induction]		Group 2: Golimumab 100 mg [Maintenance]		Group 3: Placebo [Maintenance]		Group 4: Golimumab 100 mg [Maintenance]
Arm/Group Description	Participants received golimumab 200 milligram (mg) once at Week 0 and golimumab 100 mg once at Week 2 subcutaneously (SC).		Participants who responded to golimumab induction treatment received golimumab 100 mg SC every 4 weeks (q4w) through Week 52.		Participants who responded to golimumab induction treatment received placebo SC every 4 weeks (q4w) through Week 52.		Participants who not responded to golimumab induction dosing received golimumab 100 mg SC once at Week 0 and once at Week 4, and based on clinical response every 4 week through Week 52.
All Cause Mortality
	Group1: Golimumab [Induction]		Group 2: Golimumab 100 mg [Maintenance]		Group 3: Placebo [Maintenance]		Group 4: Golimumab 100 mg [Maintenance]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group1: Golimumab [Induction]		Group 2: Golimumab 100 mg [Maintenance]		Group 3: Placebo [Maintenance]		Group 4: Golimumab 100 mg [Maintenance]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/144 (3.5%)		1/32 (3.1%)		4/31 (12.9%)		6/60 (10%)
Gastrointestinal disorders
Colitis Ulcerative	4/144 (2.8%)		0/32 (0%)		1/31 (3.2%)		5/60 (8.3%)
Infections and infestations
Cytomegalovirus Colitis	1/144 (0.7%)		0/32 (0%)		0/31 (0%)		0/60 (0%)
Herpes Zoster	0/144 (0%)		0/32 (0%)		0/31 (0%)		2/60 (3.3%)
Pharyngitis	0/144 (0%)		0/32 (0%)		0/31 (0%)		1/60 (1.7%)
Injury, poisoning and procedural complications
Hand Fracture	0/144 (0%)		0/32 (0%)		1/31 (3.2%)		0/60 (0%)
Joint Dislocation	0/144 (0%)		0/32 (0%)		1/31 (3.2%)		0/60 (0%)
Nervous system disorders
Cerebral Infarction	0/144 (0%)		0/32 (0%)		1/31 (3.2%)		0/60 (0%)
Vascular disorders
Takayasu's Arteritis	0/144 (0%)		1/32 (3.1%)		0/31 (0%)		0/60 (0%)
Other (Not Including Serious) Adverse Events
	Group1: Golimumab [Induction]		Group 2: Golimumab 100 mg [Maintenance]		Group 3: Placebo [Maintenance]		Group 4: Golimumab 100 mg [Maintenance]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/144 (25%)		26/32 (81.3%)		15/31 (48.4%)		31/60 (51.7%)
Blood and lymphatic system disorders
Anaemia	1/144 (0.7%)		0/32 (0%)		0/31 (0%)		3/60 (5%)
Gastrointestinal disorders
Abdominal Pain Upper	0/144 (0%)		2/32 (6.3%)		1/31 (3.2%)		1/60 (1.7%)
Colitis Ulcerative	7/144 (4.9%)		0/32 (0%)		2/31 (6.5%)		4/60 (6.7%)
General disorders
Injection Site Erythema	5/144 (3.5%)		5/32 (15.6%)		0/31 (0%)		1/60 (1.7%)
Injection Site Pain	0/144 (0%)		2/32 (6.3%)		0/31 (0%)		0/60 (0%)
Pyrexia	2/144 (1.4%)		2/32 (6.3%)		0/31 (0%)		2/60 (3.3%)
Infections and infestations
Gastroenteritis	0/144 (0%)		0/32 (0%)		0/31 (0%)		3/60 (5%)
Herpes Zoster	1/144 (0.7%)		0/32 (0%)		0/31 (0%)		3/60 (5%)
Influenza	0/144 (0%)		4/32 (12.5%)		1/31 (3.2%)		3/60 (5%)
Nasopharyngitis	17/144 (11.8%)		17/32 (53.1%)		7/31 (22.6%)		14/60 (23.3%)
Oral Herpes	0/144 (0%)		1/32 (3.1%)		3/31 (9.7%)		2/60 (3.3%)
Investigations
White Blood Cell Count Decreased	1/144 (0.7%)		2/32 (6.3%)		0/31 (0%)		0/60 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/144 (0.7%)		2/32 (6.3%)		1/31 (3.2%)		2/60 (3.3%)
Nervous system disorders
Headache	3/144 (2.1%)		1/32 (3.1%)		2/31 (6.5%)		1/60 (1.7%)
Psychiatric disorders
Insomnia	0/144 (0%)		0/32 (0%)		1/31 (3.2%)		3/60 (5%)
Respiratory, thoracic and mediastinal disorders
Cough	1/144 (0.7%)		2/32 (6.3%)		1/31 (3.2%)		2/60 (3.3%)
Upper Respiratory Tract Inflammation	0/144 (0%)		1/32 (3.1%)		0/31 (0%)		4/60 (6.7%)
Skin and subcutaneous tissue disorders
Eczema	0/144 (0%)		2/32 (6.3%)		2/31 (6.5%)		0/60 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.