Colitis, Ulcerative
Conditions
Brief summary
To evaluate the long-term safety of BI 655130 (SPESOLIMAB) in patients with moderate to severely active ulcerative colitis, who have completed treatment in previous trials To evaluate the long-term efficacy of BI 655130 (SPESOLIMAB) in patients with moderate to severely active ulcerative colitis, who have completed treatment in previous trials
Interventions
DRUGSpesolimab
Solution
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients, aged ≥18 years * Signed and dated written informed consent for 1368.17, in accordance with GCP and local legislation prior to admission into the trial * Women of childbearing potential (WOCBP) must be ready to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. Note: A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tuba ligation is NOT a method of permanent sterilisation. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. * Have completed treatment and the EOT visit in the previous trial and are willing and able to continue treatment in 1368.17.
Exclusion criteria
* Have experienced study treatment-limiting adverse events during induction treatment with study drug * Have developed any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exposure Adjusted Rate of Participants Reporting a Treatment Emergent Adverse Event (TEAE) | From first maintenance treatment until last maintenance treatment, plus residual effect period (REP) of 112 days, up to 1550 days. | Exposure adjusted rate of participants reporting a treatment emergent adverse event (TEAE). The exposure adjusted incidence rate (per 100 subject years) of a selected treatment emergent adverse event is defined as the number of subjects experiencing the adverse event per treatment group during time at risk divided by the total time of subjects at risk in that treatment group to contribute the event to the analysis multiplied by 100 (per 100 subject years). Only participants receiving maintenance treatment were analysed for this endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Clinical Remission at Week 336 of Maintenance Treatment | Up to 336 weeks | Proportion of patients with clinical remission at Week 336 of maintenance treatment. Clinical remission was defined as rectal bleeding score (RBS) = 0, modified endoscopic subscore \[mESS\] ≤1, stool frequency score (SFS) = 0 or 1 and drop ≥1 from baseline, and modified mayo clinical score ((MCS) ≤2). |
Countries
Austria, Belgium, Canada, Germany, Italy, Japan, Poland, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
An open-label 7-year long-term extension trial in patients with moderate-to-severe ulcerative colitis who completed treatment in previous spesolimab trials 1368-0005 (NCT03482635) Part 1 and 1368-0004 (NCT03100864).
Pre-assignment details
Only subjects that met the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all subjects as required.
Participants by arm
| Arm | Count |
|---|---|
| Spesolimab - All Patients Patients with moderate-to-severe ulcerative colitis who completed treatment in previous spesolimab induction trials. Patients were treated according to their previous trial outcome. Those who completed treatment in the previous trials showing a clinical response (CR) directly received maintenance treatment, consisting of 300 mg solution for injection of spesolimab administered as subcutaneous (s.c.) injection q4w for 336 weeks. Patients who did not achieve a clinical response in the previous trials received multiple active doses of 1200 milligrams (mg) solution for infusion of spesolimab as intravenous (i.v.) infusion every 4 weeks (q4w) for 12 weeks, as re-induction treatment. If participants reached a clinical response at Week 12 of the re-induction treatment, they switched to the maintenance treatment receiving 300 mg solution of injection of spesolimab as subcutaneous (s.c.) injection q4w for up to 336 weeks. | 79 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Maintenance Period Only | Adverse Event | 0 | 4 |
| Maintenance Period Only | Lack of Efficacy | 0 | 18 |
| Maintenance Period Only | Missing | 0 | 1 |
| Maintenance Period Only | Other not listed below | 0 | 4 |
| Maintenance Period Only | Protocol Violation | 0 | 1 |
| Maintenance Period Only | Stopped maintenance treatment due to study stop | 0 | 3 |
| Maintenance Period Only | Withdrawal by Subject | 0 | 3 |
| Re-induction Period Only | Lack of Efficacy | 7 | 0 |
| Re-induction Period Only | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Spesolimab - All Patients |
|---|---|
| Age, Continuous | 43.0 Years STANDARD_DEVIATION 14.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 11 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 65 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 1 / 34 |
| other Total, other adverse events | 14 / 57 | 24 / 34 |
| serious Total, serious adverse events | 3 / 57 | 6 / 34 |
Outcome results
Primary
Exposure Adjusted Rate of Participants Reporting a Treatment Emergent Adverse Event (TEAE)
Exposure adjusted rate of participants reporting a treatment emergent adverse event (TEAE). The exposure adjusted incidence rate (per 100 subject years) of a selected treatment emergent adverse event is defined as the number of subjects experiencing the adverse event per treatment group during time at risk divided by the total time of subjects at risk in that treatment group to contribute the event to the analysis multiplied by 100 (per 100 subject years). Only participants receiving maintenance treatment were analysed for this endpoint.
Time frame: From first maintenance treatment until last maintenance treatment, plus residual effect period (REP) of 112 days, up to 1550 days.
Population: SAF-MT: All participants who received at least one dose of maintenance treatment in this extension trial. Only participants receiving maintenance treatment were analysed for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 mg Spesolimab s.c. Maintenance Treatment [q4w] for 336 Weeks | Exposure Adjusted Rate of Participants Reporting a Treatment Emergent Adverse Event (TEAE) | 260.6 Events per 100 patient-years |
Secondary
Proportion of Patients With Clinical Remission at Week 336 of Maintenance Treatment
Proportion of patients with clinical remission at Week 336 of maintenance treatment. Clinical remission was defined as rectal bleeding score (RBS) = 0, modified endoscopic subscore \[mESS\] ≤1, stool frequency score (SFS) = 0 or 1 and drop ≥1 from baseline, and modified mayo clinical score ((MCS) ≤2).
Time frame: Up to 336 weeks
Population: Since this trial was prematurely ended and no patient achieved the Week 336 visit, no data satisfied the reporting criteria, and the endpoint could not be analysed.