Colitis, Ulcerative
Conditions
Keywords
Ulcerative Colitis, Japanese, Subcutaneous, Golimumab
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.
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.
Interventions
DRUGGolimumab
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.
OTHERPlacebo
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.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants 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. | 144 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Induction Phase | Adverse Event | 9 | 0 | 0 | 0 |
| Induction Phase | Lack of Efficacy | 10 | 0 | 0 | 0 |
| Induction Phase | Withdrawal by Subject | 2 | 0 | 0 | 0 |
| Maintenance Phase | Adverse Event | 0 | 0 | 1 | 1 |
| Maintenance Phase | Lack of Efficacy | 0 | 3 | 7 | 38 |
| Maintenance Phase | Physician Decision | 0 | 0 | 2 | 1 |
| Maintenance Phase | Pregnancy | 0 | 1 | 0 | 0 |
| Maintenance Phase | Withdrawal by Subject | 0 | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 14.74 |
| Region of Enrollment Japan | 144 Participants |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 144 | 26 / 32 | 15 / 31 | 31 / 60 |
| serious Total, serious adverse events | 5 / 144 | 1 / 32 | 4 / 31 | 6 / 60 |
Outcome results
Primary
Number of Participants Who Achieved Clinical Response Through Maintenance-Week 54 Measured Using the Mayo Score
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Achieved Clinical Response Through Maintenance-Week 54 Measured Using the Mayo Score | 6 participants |
| Golimumab | Number of Participants Who Achieved Clinical Response Through Maintenance-Week 54 Measured Using the Mayo Score | 18 participants |
Secondary
Number of Participants Who Achieved Clinical Remission at Both Maintenance-Week 30 and Week 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.
Time frame: Weeks 30 and 54
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Achieved Clinical Remission at Both Maintenance-Week 30 and Week 54 | 2 participants |
| Golimumab | Number of Participants Who Achieved Clinical Remission at Both Maintenance-Week 30 and Week 54 | 16 participants |
Secondary
Number of Participants With Mucosal Healing at Both Maintenance-Week 30 and Week 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.
Time frame: Weeks 30 and 54
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Mucosal Healing at Both Maintenance-Week 30 and Week 54 | 5 participants |
| Golimumab | Number of Participants With Mucosal Healing at Both Maintenance-Week 30 and Week 54 | 19 participants |