Clinical Trial Results:
Exploratory trial to assess mechanism of action, clinical effect, safety and tolerability of 12 weeks of treatment with BI 655130 in patients with active ulcerative colitis (UC)
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Summary
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EudraCT number |
2017-000100-20 |
Trial protocol |
DE GB BE |
Global end of trial date |
24 Oct 2019
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Results information
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Results version number |
v3(current) |
This version publication date |
24 Sep 2021
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First version publication date |
07 Nov 2020
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Other versions |
v1 , v2 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
1368-0004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03100864 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Boehringer Ingelheim
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Sponsor organisation address |
Binger Strasse 173, Ingelheim am Rhein, Germany,
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Public contact |
Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com
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Scientific contact |
Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Mar 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Oct 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to understand the mode of action of spesolimab in patients with active ulcerative colitis.
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Protection of trial subjects |
Only subjects that met all 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 patients as required.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Jun 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 4
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Country: Number of subjects enrolled |
Germany: 11
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Country: Number of subjects enrolled |
United Kingdom: 2
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Worldwide total number of subjects |
17
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EEA total number of subjects |
15
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
15
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
This was an Phase IIa multi-centre, non-randomised, uncontrolled single arm, open-label, exploratory trial to assess biomarker changes in response to Interleukin-36 signalling blockade induced by treatment with spesolimab in patients with moderate to severe active Ulcerative colitis. | ||||||
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Pre-assignment
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Screening details |
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
This was an open-label, single-arm trial.
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Arms
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Arm title
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Spesolimab 1200 mg Intravenous (i.v.) | ||||||
Arm description |
1200 milligram Spesolimab (infusion solution, BI 655130) was given for 12 weeks intravenously with a concentration of 20 milligram/milliliter every four weeks (on Day 1, Week 4, and Week 8). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Spesolimab
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Investigational medicinal product code |
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Other name |
BI 655130
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1200 milligram Spesolimab (infusion solution, BI 655130) was given for 12 weeks intravenously with a concentration of 20 milligram/milliliter every four weeks (on Day 1, Week 4, and Week 8).
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Out of the enrolled subjects, 8 were treated |
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Baseline characteristics reporting groups
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Reporting group title |
Spesolimab 1200 mg Intravenous (i.v.)
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Reporting group description |
1200 milligram Spesolimab (infusion solution, BI 655130) was given for 12 weeks intravenously with a concentration of 20 milligram/milliliter every four weeks (on Day 1, Week 4, and Week 8). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Spesolimab 1200 mg Intravenous (i.v.)
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Reporting group description |
1200 milligram Spesolimab (infusion solution, BI 655130) was given for 12 weeks intravenously with a concentration of 20 milligram/milliliter every four weeks (on Day 1, Week 4, and Week 8). | ||
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End point title |
The total number of deregulated genes comparing baseline to post treatment, analysed by gene expression of mucosal biopsies via RNA sequencing, per time point up to Week 12 [1] | ||||||||||||||||
End point description |
The total number of deregulated genes comparing baseline to post treatment, analysed by gene expression of mucosal biopsies via RNA sequencing, per time point up to Week 12. A total of 60,675 genes were evaluated, 40,586 genes were included in the differential expression analyses. Based on the raw read count values the DESeq2 method, one of the standard methods to analyse RNAseq data, was used for the gene expression analysis and to identify deregulated genes. A gene was considered deregulated with a FDR (false discovery rate) adjusted p-value < 0.01 and a fold change ≤ -1.3 or ≥ 1.3.
Completers analysis set (CAS): completed the trial medication through to end of trial visit, had a baseline and at least 1 post baseline measurement for any clinical efficacy or biomarker endpoint without any Important protocol deviation flagged for exclusion or rescue use on or after Visit 1b but prior to administration of the first dose of spesolimab.
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End point type |
Primary
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End point timeframe |
Measurements done at baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
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| Notes [2] - CAS |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percent change in C-reactive protein (CRP) from baseline to Week 12 | ||||||||
End point description |
Percent change in C-reactive protein (CRP) from baseline to Week 12 (day 85).
Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Measurements done at baseline (day -8 to -6) and week 12 (day 85).
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| Notes [3] - SAF |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent change in faecal calprotectin from baseline to Week 12 | ||||||||
End point description |
Percent change in faecal calprotectin from baseline to week 12 (day 85).
Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Measurements done at baseline (day -8 to -6) and week 12 (day 85).
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| Notes [4] - SAF |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent change in faecal lactoferrin from baseline to Week 12 | ||||||||
End point description |
Percent change in faecal lactoferrin from baseline to week 12 (day 85).
Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Measurements done at baseline (day -8 to -6) and week 12 (day 85).
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| Notes [5] - SAF |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of participants with clinical remission (defined as Mayo score ≤2 points, and all subscores ≤1 point) at Week 12 | ||||||||
End point description |
Number of participants with clinical remission (defined as Mayo score ≤2 points, and all subscores ≤1 point) at Week 12. The Mayo score is a composite disease activity score consisting of 4 items or subscores: stool frequency (relative to normal), rectal bleeding, physician’s global assessment (PGA), and endoscopic appearance. The overall range of the Mayo score was 0 to 12 (higher scores being worse) and each subscore had a range of 0 to 3.
Full analysis set (FAS): patients who received at least 1 dose of study drug, who had a baseline and at least 1 post baseline measurement for any clinical efficacy or biomarker endpoint without any Important protocol deviation flagged for exclusion or rescue use on or after Visit 1b but prior to administration of the first dose of spesolimab.
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End point type |
Secondary
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End point timeframe |
Week 12 (day 85) following start of treatment.
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| Notes [6] - FAS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of patients with drug related adverse events (AEs) | ||||||||
End point description |
Number of patients with drug related adverse events (AEs) during the on-treatment period.
Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Date of start of infusion of first study drug (Day 1) till the date of end of infusion of last study drug (day 57) + 140 days at 11:59 p.m., up to 197 days.
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| Notes [7] - SAF |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Date of start of infusion of first study drug (Day 1) till the date of end of infusion of last study drug (day 57) + 140 days at 11:59 p.m., up to 197 days.
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Adverse event reporting additional description |
Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
Spesolimab 1200 mg Intravenous (i.v.)
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Reporting group description |
1200 milligram Spesolimab (infusion solution, BI 655130) was given for 12 weeks intravenously with a concentration of 20 milligram/milliliter every four weeks (on Day 1, Week 4, and Week 8). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Jan 2018 |
Global Amendment 1:
- Safety information and PK modelling were updated with data from trials 1368.1 and
1368.2. As a result of these changes, the lower body weight limit of 60 kg was deleted as
it was no longer required
- Sigmoidoscopy at 4 hours after the first i.v. infusion was deleted to reduce the overall
number of sigmoidoscopies in the trial. All biopsy samples had to be obtained prior to
trial treatment administration
- The trial design was updated to add the option of long-term treatment in trial 1368-0017
for patients who completed 12 weeks of treatment in this exploratory trial
- The trial population was extended to patients who had been previously treated with TNF
antagonist(s) but who did not stop that treatment due to primary non-response or lack of
response. This change was made to facilitate recruitment. The last dose of TNF
antagonist(s) had to be at least 8 weeks or 3 half-lives (whichever was longer) from
screening
- Further guidance to investigators was added regarding infusion reactions, CRS and
infections
- Infusion reactions including anaphylactic reactions, CRS and opportunistic and
Mycobacterium tuberculosis infections were added to AESIs for consistency across the
spesolimab programme
- The section on equivalent doses of corticosteroids was updated to add budesonide and to
remove 16-methylprednisolone |
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18 May 2018 |
Global Amendment 2: - Following feedback from experts, the deletion of sigmoidoscopy with biopsy sample
collection and blood sampling for gene expression and methylation pattern analysis at
4 hours after the first i.v. infusion (Amendment 1) was reversed and was re-included in
the trial - Additional study sites were planned to be included |
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03 Apr 2019 |
Global Amendment 3: - The upper age limit was increased from 65 years to 75 years to facilitate recruitment and
for consistency with more recent trials in the programme |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
