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 active ulcerative colitis (UC) (sores in the colon).
Detailed description
This is a randomized (study medication assigned by chance), double-blind (neither the Physician nor the participant know about the study medication), placebo-controlled (an inactive substance; a pretend treatment \[with no drug in it\] that is compared in a clinical trial with a drug to test if the drug has a real effect), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different interventions \[treatments\]) study to evaluate an appropriate intravenous (through a vein in the arm) golimumab induction dose and to demonstrate the safety and efficacy of intravenous induction dosing with golimumab in participants with moderately to severely active UC. 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 at Week 16. The duration of study will be 6 weeks for participants who enter the 1-year golimumab maintenance study and 16 weeks for participant who do not enter the 1-year golimumab maintenance study.There are 2 parts in this study. Part 1 is Phase 2 dose-ranging portion of study. Participants enrolled in Part 1, will receive a single intravenous infusion of either matching placebo for golimumab or 1 milligram (mg) per kilogram(kg), 2 mg per kg or 4 mg per kg of golimumab. Part 2 of the study is called dose-confirming and newly enrolled participants will receive same doses studied in Part 1, until the doses for Part 2 are selected and Phase 3 begins. At the time that the final doses are selected, all newly enrolled participants will receive 1 of the selected doses or matching placebo; this is the start of the Phase 3 portion of the study. Participants will primarily be assessed using Mayo Score (it is a score developed for measuring disease activity). Participants' safety and quality of life will also be monitored throughout the study.
Interventions
OTHERPlacebo
Matching placebo for golimumab, intravenous infusion administered at Week 0
DRUGGolimumab 1 mg per kg
Golimumab 1 mg per kg intravenous (IV) infusion administered at Week 0
DRUGGolimumab 2 mg per kg
Golimumab 2 mg per kg intravenous (IV) infusion administered at Week 0
DRUGGolimumab 4 mg per kg
Golimumab 4 mg per kg intravenous (IV) infusion at Week 0
Sponsors
Merck Sharp & Dohme LLC
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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 (5-ASAs), oral corticosteroids, 6-mercaptopurine (6-MP) and azathioprine (AZA) * 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 TB
Exclusion criteria
* Participants with previous 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 (cm) 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 | 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 a 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 | 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 a 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. |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, France, Germany, Hungary, India, Israel, Latvia, Lithuania, Netherlands, New Zealand, Poland, Romania, Russia, Serbia, Slovakia, Sweden, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo for golimumab, intravenous (IV) (through a vein in the arm) infusion administered at Week 0. | 77 |
| Golimumab 1 mg Per kg Golimumab 1 mg per kg intavenous infusion was administered at Week 0. | 62 |
| Golimumab 2 mg Per kg Golimumab 2 mg per kg intravenous infusion was administered at Week 0. | 75 |
| Golimumab 4 mg Per kg Golimumab 4 mg per kg intavenous infusion was administered at Week 0. | 77 |
| Total | 291 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 |
| Overall Study | Other | 6 | 3 | 2 | 2 |
| Overall Study | Withdrawal of consent | 2 | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Golimumab 1 mg Per kg | Golimumab 2 mg Per kg | Golimumab 4 mg Per kg |
|---|---|---|---|---|---|
| Age Continuous | 41 Years STANDARD_DEVIATION 13.74 | 40.9 Years STANDARD_DEVIATION 12.58 | 40.7 Years STANDARD_DEVIATION 15.51 | 42.3 Years STANDARD_DEVIATION 13.14 | 39.9 Years STANDARD_DEVIATION 14.07 |
| Sex: Female, Male Female | 117 Participants | 30 Participants | 21 Participants | 39 Participants | 27 Participants |
| Sex: Female, Male Male | 174 Participants | 47 Participants | 41 Participants | 36 Participants | 50 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 | 15 / 77 | 13 / 63 | 15 / 74 | 9 / 76 |
| serious Total, serious adverse events | 3 / 77 | 2 / 63 | 3 / 74 | 3 / 76 |
Outcome results
Primary
Number of Participants With Clinical Response
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 a 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: The efficay analysis population included all the participants who were randomly assigned to receive study medication. Here 'N' signifies participants who were evaluated for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinical Response | 22 Participants |
| Golimumab 1 mg Per kg | Number of Participants With Clinical Response | 22 Participants |
| Golimumab 2 mg Per kg | Number of Participants With Clinical Response | 33 Participants |
| Golimumab 4 mg Per kg | Number of Participants With Clinical Response | 32 Participants |
p-value: 0.467Chi-squared
p-value: 0.081Chi-squared
p-value: 0.145Chi-squared
Secondary
Number of Participants With Clinical Remission
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 a 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: The efficay analysis population included all the participants who were randomly assigned to receive study medication. Here 'N' signifies participants who were evaluated for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinical Remission | 8 Participants |
| Golimumab 1 mg Per kg | Number of Participants With Clinical Remission | 6 Participants |
| Golimumab 2 mg Per kg | Number of Participants With Clinical Remission | 12 Participants |
| Golimumab 4 mg Per kg | Number of Participants With Clinical Remission | 10 Participants |
p-value: 0.832Chi-squared
p-value: 0.37Chi-squared
p-value: 0.702Chi-squared