Ulcerative Colitis
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of golimumab in maintaining a clinical response in participants with moderate-to-severe ulcerative colitis.
Detailed description
This study consists of a 1 week screening period, a 54 week treatment period, and a 12 week follow-up period, requiring a total of 7 trial site visits: Visit 1(screening visit, Week -1), Visit 2 (enrollment visit, Day 0), Visit 3 (Week 2), Visit 4 (Week 6), Visit 5 (Week 30) and Visit 6 (Week 54) and Visit 7 (follow-up visit, Week 66).
Interventions
DRUGGolimumab
50mg or 100mg solution for injection; subcutaneous injection
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of ulcerative colitis for at least 3 months with moderate-to-severe disease at enrollment. * Has a rectal bleeding subscore of 1 or more at baseline. * No evidence of active, or latent, or inadequately treated infection with Mycobacterium tuberculosis (TB). * Must be eligible to start golimumab treatment according to the summary of product characteristics. * Must be naïve to anti-tumor necrosis factor (anti-TNF) therapy. * Women of childbearing potential or men capable of fathering children must agree to use adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implant, surgical sterilization). * Women of childbearing potential must test negative for pregnancy at screening. * Any prior azathioprine / 6-mercaptopurine use was initiated at least 12 weeks prior to enrollment with either stable dosing or discontinued treatment for the 4 weeks immediately prior to enrollment.
Exclusion criteria
* Clinical signs of ischaemic colitis, fulminant colitis or toxic megacolon. * Has evidence of pathogenic bowel infection. * Has a diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn's disease. * Has had surgery as a treatment for ulcerative colitis, or is likely to require surgery. * Has ulcerative colitis which is confined to a proctitis (distal 15 cm or less). * Has a current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease. * Has a current immunization with any live virus vaccine or history of immunization with any live virus vaccine within 3 months of baseline. * Pregnant or lactating, or planning pregnancy while enrolled in the study. * Has received agents that deplete B or T cells (eg, rituximab or alemtuzumab) within 12 months prior to study inclusion, or continue to manifest depletion of B or T cells more than 12 months after completion of therapy with lymphocyte-depleting agents. * Has received cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 8 weeks prior to study inclusion. * Has used any investigational drugs within 30 days of Screening. * Has a known hypersensitivity to human immunoglobulin proteins or other components of golimumab. * Has received methotrexate within 12 weeks prior to enrollment * Has received rectal corticosteroids or rectal 5-aminosalicylic acid (5-ASA) compounds within 2 weeks prior to enrollment (may be commenced if required after Week 6 in the study)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Meeting Partial Mayo Score Response Criteria Through Week 54 | Baseline (Week 0), Week 6, Week 30, Week 54 | The Partial Mayo Score (Mayo Score without endoscopy) measures severity of ulcerative colitis. Three sub-scores for stool frequency, rectal bleeding, and physician's global assessment are each graded from 0 to 3 with higher scores indicating more severe disease. Individual sub-scores are then summed to provide the total score ranging from 0 (normal or inactive disease) to 9 (severe disease). Clinical response is defined as a decrease in PMS of ≥2 points and ≥30% from baseline, plus either a decrease in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1. In this outcome measure, the percentage of participants starting treatment at the start of the Induction Phase (Baseline) who obtained clinical response by the end of the Induction Phase (i.e., by Week 6) and maintained clinical response through Week 54 (i.e., had positive clinical responses at both Weeks 30 and 54) are estimated. |
Countries
United Kingdom
Participant flow
Pre-assignment details
A total of 225 participants were screened; 205 participants started treatment after meeting eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| Golimumab The first induction dose of SC golimumab 200 mg was administered at Day 0. The second induction dose of SC golimumab 100 mg was administered two weeks later at Week 2. Responders at Week 6 received a maintenance dose of golimumab (50 mg for participants with a body weight \<80 kg or 100 mg for participants with a body weight ≥80 kg) every 4 weeks during the Maintenance Phase for 48 weeks, yielding a total of 54 weeks treatment. | 205 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Induction Phase | Adverse Event | 7 |
| Induction Phase | Lack of Efficacy | 14 |
| Induction Phase | Physician Decision | 4 |
| Induction Phase | Pregnancy | 1 |
| Induction Phase | Relapse/Recurrence | 7 |
| Induction Phase | Withdrawal by Subject | 2 |
| Maintenance Phase & Follow-up | Adverse Event | 22 |
| Maintenance Phase & Follow-up | Lack of Efficacy | 23 |
| Maintenance Phase & Follow-up | Lost to Follow-up | 1 |
| Maintenance Phase & Follow-up | Non-compliance with study drug | 2 |
| Maintenance Phase & Follow-up | Physician Decision | 10 |
| Maintenance Phase & Follow-up | Pregnancy | 1 |
| Maintenance Phase & Follow-up | Protocol Violation | 11 |
| Maintenance Phase & Follow-up | Relapse/recurrence | 29 |
| Maintenance Phase & Follow-up | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Golimumab |
|---|---|
| Age, Continuous | 39.3 years STANDARD_DEVIATION 15.09 |
| Age, Customized Adolescents (12-17 years) | 3 Participants |
| Age, Customized Adults (between 18 and 64 years) | 184 Participants |
| Age, Customized From 65 to 84 years | 18 Participants |
| Partial Mayo Score | 6.4 Units on a scale STANDARD_DEVIATION 1.4 |
| Sex: Female, Male Female | 82 Participants |
| Sex: Female, Male Male | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 82 / 205 |
| serious Total, serious adverse events | 49 / 205 |
Outcome results
Primary
Percentage of Participants Meeting Partial Mayo Score Response Criteria Through Week 54
The Partial Mayo Score (Mayo Score without endoscopy) measures severity of ulcerative colitis. Three sub-scores for stool frequency, rectal bleeding, and physician's global assessment are each graded from 0 to 3 with higher scores indicating more severe disease. Individual sub-scores are then summed to provide the total score ranging from 0 (normal or inactive disease) to 9 (severe disease). Clinical response is defined as a decrease in PMS of ≥2 points and ≥30% from baseline, plus either a decrease in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1. In this outcome measure, the percentage of participants starting treatment at the start of the Induction Phase (Baseline) who obtained clinical response by the end of the Induction Phase (i.e., by Week 6) and maintained clinical response through Week 54 (i.e., had positive clinical responses at both Weeks 30 and 54) are estimated.
Time frame: Baseline (Week 0), Week 6, Week 30, Week 54
Population: The analysis population for the evaluation of efficacy during the maintenance period was the Full Analysis Set (FAS205) consisting of participants who received at least 1 dose of golimumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab | Percentage of Participants Meeting Partial Mayo Score Response Criteria Through Week 54 | 24.9 Percentage of Participants |