Colitis, Ulcerative
Conditions
Brief summary
The purpose of this study is to evaluate the clinical efficacy and safety of combination therapy with guselkumab and golimumab in participants with moderately to severely active ulcerative colitis (UC).
Interventions
Guselkumab Dose 1 will be administered as IV infusion.
Guselkumab Dose 2 will be administered as SC injection.
DRUGGolimumab Dose 1
Golimumab Dose 1 will be administered as SC injection.
DRUGGolimumab Dose 2
Golimumab Dose 2 will be administered as SC injection.
DRUGPlacebo
Placebo will be administered.
Sponsors
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed clinical diagnosis of ulcerative colitis (UC) at least 3 months before screening * Moderately to severely active UC as defined by Mayo score * History of inadequate response to or failure to tolerate conventional therapy * Has screening laboratory test results within the study protocol defined parameters * A woman of childbearing potential must have a negative highly sensitive serum (beta human chorionic gonadotropin) pregnancy test result at screening and a negative urine pregnancy test result at Week 0
Exclusion criteria
* Has severe extensive colitis as defined in the study protocol * Has UC limited to the rectum only or to less than (\<) 20 centimeter (cm) of the colon * Has a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, before screening * Has any known malignancy or has a history of malignancy (with the exception of basal cell carcinoma; squamous cell carcinoma in situ of the skin; or cervical carcinoma in situ that has been treated with no evidence of recurrence; or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years before screening) * Has known allergies, hypersensitivity, or intolerance to guselkumab or golimumab or their excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combination Phase: Percentage of Participants Who Achieved Clinical Response at Week 12 | Week 12 | Clinical response was defined as a decrease from baseline in the Mayo score greater than or equal to (\>=) 30 percent (%) and \>=3 points with either a decrease from baseline in the rectal bleeding subscore (RBS) \>=1 or a RBS of 0 or 1. The Mayo score was calculated as the sum of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings - each with score range of 0 (normal activity) to 3 (severe activity) and a total score range of 0 to 12 points. A score of 3 to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 12 points indicates severely active disease. Higher scores indicate more severity. This outcome measure was analyzed for combination phase only as preplanned in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combination Phase: Percentage of Participants Who Achieved Clinical Remission at Week 12 | Week 12 | Clinical remission was defined as the Mayo score less than or equal to (\<=) 2 with no individual subscore greater than (\>) 1. The Mayo score was calculated as the sum of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each with score range of 0 (normal activity) to 3 (severe activity) and a total score range of 0 to 12 points. A score of 3 to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 12 points indicates severely active disease. Higher scores indicate more severity. This outcome measure was analyzed for combination phase only as preplanned in the protocol. |
Countries
Argentina, Australia, Brazil, Germany, Mexico, Poland, Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Golimumab Monotherapy Participants received golimumab 200 milligrams (mg) as subcutaneous (SC) injection at Week 0 followed by golimumab 100 mg as SC injection at Weeks 2, 6, 10, 14, 18, 22, 26, 30 and 34. Participants received placebo as intravenous (IV) infusion as Weeks 0, 4, 8 and as SC injection at Weeks 16, 24, 32 to maintain the blind. Participants were then followed up for safety from Week 38 to Week 50 (end of study \[EOS\]). | 72 |
| Guselkumab Monotherapy Participants received guselkumab 200 mg as IV infusion at Weeks 0, 4 and 8 followed by guselkumab 100 mg as SC injection at Weeks 16, 24 and 32. Participants received placebo as SC injection at Weeks 0, 2, 6, 10, 14, 18, 22, 26, 30, and 34 to maintain the blind. Participants were then followed up for safety from Week 38 to Week 50 (EOS). | 71 |
| Combination Therapy Participants received guselkumab 200 mg as IV infusion followed by golimumab 200 mg as SC injection at Weeks 0. Participants received guselkumab 200 mg as IV infusion at Weeks 4 and 8, golimumab 100 mg as SC injection at Weeks 2, 6 and 10 and placebo as SC injection at Weeks 14, 18, 22, 26, 30, and 34 to maintain the blind. Participants were then followed up for safety from Week 38 to Week 50 (EOS). | 71 |
| Total | 214 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Combination Phase ( Week 0- Week 12) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Combination Phase ( Week 0- Week 12) | COVID-19 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Combination Phase ( Week 0- Week 12) | Other | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Combination Phase ( Week 0- Week 12) | Withdrawal by Subject | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monotherapy Phase (Week 12-Week 38) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Monotherapy Phase (Week 12-Week 38) | Death | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Monotherapy Phase (Week 12-Week 38) | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Monotherapy Phase (Week 12-Week 38) | Other | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 |
| Monotherapy Phase (Week 12-Week 38) | Withdrawal by Subject | 0 | 0 | 0 | 4 | 1 | 1 | 0 | 0 | 0 |
| Safety Follow-up (Week 38- Week 50) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Safety Follow-up (Week 38- Week 50) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Safety Follow-up (Week 38- Week 50) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 6 | 2 |
| Safety Follow-up (Week 38- Week 50) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Combination Therapy | Total | Golimumab Monotherapy | Guselkumab Monotherapy |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 213 Participants | 72 Participants | 70 Participants |
| Age, Continuous | 37.8 years STANDARD_DEVIATION 11.69 | 38.4 years STANDARD_DEVIATION 11.96 | 38.1 years STANDARD_DEVIATION 10.47 | 39.1 years STANDARD_DEVIATION 13.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 15 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 66 Participants | 199 Participants | 68 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 70 Participants | 208 Participants | 67 Participants | 71 Participants |
| Region of Enrollment ARGENTINA | 3 Participants | 4 Participants | 0 Participants | 1 Participants |
| Region of Enrollment AUSTRALIA | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Region of Enrollment BRAZIL | 4 Participants | 9 Participants | 2 Participants | 3 Participants |
| Region of Enrollment GERMANY | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Region of Enrollment MEXICO | 0 Participants | 4 Participants | 2 Participants | 2 Participants |
| Region of Enrollment POLAND | 14 Participants | 40 Participants | 15 Participants | 11 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 30 Participants | 71 Participants | 19 Participants | 22 Participants |
| Region of Enrollment UKRAINE | 16 Participants | 68 Participants | 27 Participants | 25 Participants |
| Region of Enrollment UNITED STATES | 2 Participants | 12 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 37 Participants | 98 Participants | 30 Participants | 31 Participants |
| Sex: Female, Male Male | 34 Participants | 116 Participants | 42 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 71 | 0 / 71 | 0 / 67 | 0 / 70 | 1 / 71 | 0 / 58 | 1 / 65 | 0 / 60 |
| other Total, other adverse events | 19 / 72 | 16 / 71 | 14 / 71 | 12 / 67 | 16 / 70 | 14 / 71 | 3 / 58 | 2 / 65 | 0 / 60 |
| serious Total, serious adverse events | 1 / 72 | 2 / 71 | 1 / 71 | 3 / 67 | 1 / 70 | 3 / 71 | 0 / 58 | 2 / 65 | 0 / 60 |
Outcome results
Primary
Combination Phase: Percentage of Participants Who Achieved Clinical Response at Week 12
Clinical response was defined as a decrease from baseline in the Mayo score greater than or equal to (\>=) 30 percent (%) and \>=3 points with either a decrease from baseline in the rectal bleeding subscore (RBS) \>=1 or a RBS of 0 or 1. The Mayo score was calculated as the sum of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings - each with score range of 0 (normal activity) to 3 (severe activity) and a total score range of 0 to 12 points. A score of 3 to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 12 points indicates severely active disease. Higher scores indicate more severity. This outcome measure was analyzed for combination phase only as preplanned in the protocol.
Time frame: Week 12
Population: Efficacy analyses were based on the full analysis set (FAS), which included all randomized participants who received at least 1 (partial or complete) dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Phase: Golimumab Monotherapy | Combination Phase: Percentage of Participants Who Achieved Clinical Response at Week 12 | 61.1 Percentage of participants |
| Combination Phase: Guselkumab Monotherapy | Combination Phase: Percentage of Participants Who Achieved Clinical Response at Week 12 | 74.6 Percentage of participants |
| Combination Phase: Combination Therapy | Combination Phase: Percentage of Participants Who Achieved Clinical Response at Week 12 | 83.1 Percentage of participants |
Secondary
Combination Phase: Percentage of Participants Who Achieved Clinical Remission at Week 12
Clinical remission was defined as the Mayo score less than or equal to (\<=) 2 with no individual subscore greater than (\>) 1. The Mayo score was calculated as the sum of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each with score range of 0 (normal activity) to 3 (severe activity) and a total score range of 0 to 12 points. A score of 3 to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 12 points indicates severely active disease. Higher scores indicate more severity. This outcome measure was analyzed for combination phase only as preplanned in the protocol.
Time frame: Week 12
Population: Efficacy analyses were based on the FAS, which included all randomized participants who received at least 1 (partial or complete) dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Phase: Golimumab Monotherapy | Combination Phase: Percentage of Participants Who Achieved Clinical Remission at Week 12 | 22.2 Percentage of participants |
| Combination Phase: Guselkumab Monotherapy | Combination Phase: Percentage of Participants Who Achieved Clinical Remission at Week 12 | 21.1 Percentage of participants |
| Combination Phase: Combination Therapy | Combination Phase: Percentage of Participants Who Achieved Clinical Remission at Week 12 | 36.6 Percentage of participants |