Colitis, Ulcerative
Conditions
Keywords
Colitis, Ulcerative, Golimumab, CNTO 148
Brief summary
The purpose of this study is to assess the effects (good and bad) of golimumab (CNTO 148) therapy in participants with ulcerative colitis (UC).
Detailed description
This is a multi-center (conducted in more than one center), randomized (study medication assigned by chance), double-blind (neither the physician nor the participant know about the study medication), placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different interventions) study to evaluate the safety and efficacy of golimumab in participants with moderately to severely active UC. There are 2 parts in this study. Part 1 is Phase 2 dose-ranging portion of study. Participants enrolled in Part 1, will receive subcutaneous (under the skin by way of a needle) injections of placebo, golimumab 100 milligram (mg), 200 mg, or 400 mg at Week 0, followed by subcutaneous injections of placebo, golimumab 50 mg, 100 mg, or 200 mg respectively at Week 2. Part 2 is Phase 3 dose-confirming portion of study and newly enrolled participants will receive same doses studied in Part 1, until the doses for Part 2 are selected. At the time that the final doses are selected, all newly enrolled participants will receive 1 of the selected doses or matching placebo. At Week 6, participants will be asked to participate in an additional 1-year maintenance study. Participants not entering the 1-year golimumab maintenance study will be evaluated for safety 16 weeks after last administration of study agent. The duration of study will be 6 weeks for participants who enter the 1-year golimumab maintenance study and 16 weeks after last administration of study agent for participants who do not enter the 1-year golimumab maintenance study. Efficacy of the participants will primarily be evaluated by clinical response at Week 6. Participants' safety will be monitored throughout the study.
Interventions
BIOLOGICALPlacebo
Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2.
BIOLOGICALGolimumab 100 mg
Golimumab 100 mg subcutaneous injection administered at Week 0 for Golimumab 100 mg -\> 50 mg arm group and at Week 2 for Golimumab 200 mg -\> 100 mg arm group.
BIOLOGICALGolimumab 200 mg
Golimumab 200 mg subcutaneous injection administered at Week 0 for Golimumab 200 mg -\> 100 mg arm group and at Week 2 for Golimumab 400 mg -\> 200 mg arm group.
BIOLOGICALGolimumab 400 mg
Golimumab 400 mg subcutaneous injection administered at Week 0 for Golimumab 400 mg -\> 200 mg arm group.
BIOLOGICALGolimumab 50 mg
Golimumab 50 mg subcutaneous injection administered at Week 2 for Golimumab 100 mg -\> 50 mg arm group.
Sponsors
Merck Sharp & Dohme LLC
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants diagnosed with moderately to severely active ulcerative colitis (UC) defined by a Mayo score of 6 to 12 inclusive at Baseline (Week 0), including an endoscopic (examination of an internal part of the body with a lighted tube; looking at a part of the body with a lighted tube) subscore of greater than or equal to 2 * Participants must have biopsy results (collected at the screening endoscopy (procedure or obtained within the last year) consistent with the diagnosis of UC * Participants either currently receiving treatment with, or have a history of failure to respond to, or tolerate, at least 1 of the following therapies: oral 5-aminosalicylate, oral corticosteroids, 6-mercaptopurine and azathioprine * Participants with current dependency or with a history of corticosteroid dependency (i.e., an inability to successfully taper corticosteroids without a return of the symptoms of UC) * Not have a diagnosis of active tuberculosis * Participants with negative stool test for enteric (by way of the intestines) pathogens
Exclusion criteria
* Participants with prior exposure to biologic anti-tumor necrosis factor (TNF) agents * Participants with severe extensive UC that is likely to require a colectomy (surgery to remove part or all of the colon) within 12 weeks of study entry * Participants having UC limited to the rectum only or to less than 20 centimeter of the colon * Presence of a stoma (an artificial permanent opening especially in the abdominal wall made in surgical procedures) or presence of a fistula * Participants with a history of extensive colonic resection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response at Week 6 | Baseline, Week 6 | Clinical response is defined as decrease from baseline in Mayo score by greater than or equal to 30 percent and greater than or equal to 3, with either a decrease from baseline in rectal bleeding sub-score of greater than or equal to 1 or a rectal bleeding sub-score of 0 or 1. The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings, and physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Remission at Week 6 | Week 6 | Clinical remission is defined as a Mayo score of less than or equal to 2, with no individual sub-score greater than 1. The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings, and physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12. |
| Number of Participants With Mucosal Healing at Week 6 | Week 6 | Mucosal healing is determined from the endoscopy sub-score of the Mayo score. Mucosal healing is defined as an endoscopy sub-score of 0 or 1. Higher score indicates higher severity of disease. Endoscopy sub-score ranges from 0 (normal or inactive disease) to 3 (severe disease; spontaneous bleeding and ulceration). |
| Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | Baseline to Week 6 | The IBDQ is used to measure disease specific quality of life on a 32 Likert-scaled items questionnaire. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function and social function with scores ranging from 10 to 70, 5 to 35, 12 to 84 and 5 to 35 respectively and the total score ranges from 32 to 224. Higher scores indicate better health related quality of life. |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Hungary, India, Israel, Japan, Lithuania, Netherlands, New Zealand, Poland, Romania, Russia, Serbia, Slovakia, South Africa, Sweden, Ukraine, United States
Participant flow
Pre-assignment details
Participants were assigned to Placebo, Golimumab 100 mg-\>50 mg, Golimumab 200 mg-\>100 mg and Golimumab 400 mg-\>200 mg groups for dose selection. Efficacy results were reported for only newly enrolled participants assigned to Placebo, Golimumab 200 mg-\>100 mg and Golimumab 400 mg-\>200 mg groups after dose-selection as per planned analysis.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo subcutaneous injection (given under the skin by way of a needle) matched to golimumab administered at Week 0 and Week 2. | 331 |
| Golimumab 100 mg -> 50 mg Golimumab 100 milligram (mg) subcutaneous injection was administered at Week 0 and dose was decreased to 50 mg at Week 2. | 72 |
| Golimumab 200 mg -> 100 mg Golimumab 200 mg subcutaneous injection was administered at Week 0 and dose was decreased to 100 mg at Week 2. | 331 |
| Golimumab 400 mg -> 200 mg Golimumab 400 mg subcutaneous injection was administered at Week 0 and dose was decreased to 200 mg at Week 2. | 331 |
| Total | 1,065 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 1 | 1 |
| Overall Study | Other | 3 | 1 | 2 | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Golimumab 100 mg -> 50 mg | Golimumab 200 mg -> 100 mg | Golimumab 400 mg -> 200 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39 Years STANDARD_DEVIATION 13.04 | 40.9 Years STANDARD_DEVIATION 12.19 | 40 Years STANDARD_DEVIATION 13.54 | 40.7 Years STANDARD_DEVIATION 13.75 | 40 Years STANDARD_DEVIATION 13.37 |
| Sex: Female, Male Female | 156 Participants | 32 Participants | 151 Participants | 130 Participants | 469 Participants |
| Sex: Female, Male Male | 175 Participants | 40 Participants | 180 Participants | 201 Participants | 596 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 | 61 / 330 | 18 / 71 | 54 / 331 | 55 / 332 |
| serious Total, serious adverse events | 20 / 330 | 3 / 71 | 10 / 331 | 15 / 332 |
Outcome results
Primary
Number of Participants With Clinical Response at Week 6
Clinical response is defined as decrease from baseline in Mayo score by greater than or equal to 30 percent and greater than or equal to 3, with either a decrease from baseline in rectal bleeding sub-score of greater than or equal to 1 or a rectal bleeding sub-score of 0 or 1. The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings, and physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12.
Time frame: Baseline, Week 6
Population: Efficacy analysis population included all the participants who were randomly assigned to the study after the dose selection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinical Response at Week 6 | 76 Participants |
| Golimumab 200 mg -> 100 mg | Number of Participants With Clinical Response at Week 6 | 129 Participants |
| Golimumab 400 mg -> 200 mg | Number of Participants With Clinical Response at Week 6 | 141 Participants |
p-value: <0.0001Chi-squared
p-value: <0.0001Chi-squared
Secondary
Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6
The IBDQ is used to measure disease specific quality of life on a 32 Likert-scaled items questionnaire. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function and social function with scores ranging from 10 to 70, 5 to 35, 12 to 84 and 5 to 35 respectively and the total score ranges from 32 to 224. Higher scores indicate better health related quality of life.
Time frame: Baseline to Week 6
Population: Efficacy analysis population included all the participants who were randomly assigned to the study after the dose selection. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | Baseline | 129.6 Units on a Scale | Standard Deviation 32.61 |
| Placebo | Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | Change at Week 6 | 14.8 Units on a Scale | Standard Deviation 31.25 |
| Golimumab 200 mg -> 100 mg | Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | Baseline | 131.7 Units on a Scale | Standard Deviation 33.93 |
| Golimumab 200 mg -> 100 mg | Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | Change at Week 6 | 27.0 Units on a Scale | Standard Deviation 33.72 |
| Golimumab 400 mg -> 200 mg | Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | Baseline | 127.2 Units on a Scale | Standard Deviation 33.9 |
| Golimumab 400 mg -> 200 mg | Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | Change at Week 6 | 26.9 Units on a Scale | Standard Deviation 34.28 |
p-value: <0.0001ANOVA
p-value: <0.0001ANOVA
Secondary
Number of Participants With Clinical Remission at Week 6
Clinical remission is defined as a Mayo score of less than or equal to 2, with no individual sub-score greater than 1. The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings, and physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12.
Time frame: Week 6
Population: Efficacy analysis population included all the participants who were randomly assigned to the study after the dose selection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinical Remission at Week 6 | 16 Participants |
| Golimumab 200 mg -> 100 mg | Number of Participants With Clinical Remission at Week 6 | 45 Participants |
| Golimumab 400 mg -> 200 mg | Number of Participants With Clinical Remission at Week 6 | 46 Participants |
p-value: <0.0001Chi-squared
p-value: <0.0001Chi-squared
Secondary
Number of Participants With Mucosal Healing at Week 6
Mucosal healing is determined from the endoscopy sub-score of the Mayo score. Mucosal healing is defined as an endoscopy sub-score of 0 or 1. Higher score indicates higher severity of disease. Endoscopy sub-score ranges from 0 (normal or inactive disease) to 3 (severe disease; spontaneous bleeding and ulceration).
Time frame: Week 6
Population: Efficacy analysis population included all the participants who were randomly assigned to the study after the dose selection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Mucosal Healing at Week 6 | 72 Participants |
| Golimumab 200 mg -> 100 mg | Number of Participants With Mucosal Healing at Week 6 | 107 Participants |
| Golimumab 400 mg -> 200 mg | Number of Participants With Mucosal Healing at Week 6 | 116 Participants |
p-value: 0.0014Chi-squared
p-value: 0.0001Chi-squared