This Study Tests How BI 655130 Works in Patients With Active Ulcerative Colitis. The Study Also Tests How Well BI 655130 is Tolerated and Whether it Helps the Patients

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03100864
• Collaborator: (none)
• Enrollment: 8
• Locations: 4
• Arm: 1
• Actual Duration (Months): 29.1
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this trial is to understand the mechanism of action of BI655130 in patients with UC

Secondary objectives are to explore clinical effect, safety and tolerability (including immunogenicity) of BI 655130 treatment

Condition or Disease	Intervention/Treatment	Phase
Colitis, Ulcerative	Drug: Spesolimab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: May 22, 2017
• Actual Primary Completion Date: Aug 5, 2019
• Actual Study Completion Date: Oct 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Spesolimab	Drug: Spesolimab; 12 weeks treatment

Outcome Measures

Primary Outcome Measures

1. 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 [Measurements done at baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12).]

   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.

Secondary Outcome Measures

1. Percent Change in C-reactive Protein (CRP) From Baseline to Week 12 [Measurements done at baseline (day -8 to -6) and week 12 (day 85).]

   Percent change in C-reactive protein (CRP) from baseline to Week 12 (day 85).

2. Percent Change in Faecal Calprotectin From Baseline to Week 12 [Measurements done at baseline (day -8 to -6) and week 12 (day 85).]

   Percent change in faecal calprotectin from baseline to week 12 (day 85).

3. Percent Change in Faecal Lactoferrin From Baseline to Week 12 [Measurements done at baseline (day -8 to -6) and week 12 (day 85).]

   Percent change in faecal lactoferrin from baseline to week 12 (day 85).

4. Number of Participants With Clinical Remission (Defined as Mayo Score ≤2 Points, and All Subscores ≤1 Point) at Week 12 [Week 12 (day 85) following start of treatment.]

   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.

5. Number of Patients With Drug Related Adverse Events (AEs) [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.]

   Number of patients with drug related adverse events (AEs) during the on-treatment period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 - 75 years at screening

• Diagnosis of UC >= 3 months prior to screening.

• Moderately to severely active UC as confirmed by Mayo Score ≥6

• Receiving conventional, non-biologic therapy for UC.

• Negative colon cancer screening

• Further inclusion criteria apply

Exclusion Criteria:

• Prior use of any biological treatment in the past (e.g.integrin inhibitors, IL12/23 or IL23 inhibitors, any investigational biological drugs)

• Extensive colonic resection

• Evidence of infection with C. difficile or other intestinal pathogen < 30 days prior to screening

• Active or latent tuberculosis

• Further exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UZ Leuven	Leuven		Belgium	3000
2	Asklepios Kliniken Westklinikum Hamburg	Hamburg		Germany	22559
3	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel		Germany	24105
4	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 3, 2019
• Statistical Analysis Plan - Dec 6, 2019

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03100864
• Other Study ID Numbers: 1368-0004; 2017-000100-20
• First Posted: Apr 4, 2017
• Last Update Posted: Dec 22, 2020
• Last Verified: Nov 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer

Study Results

Participant Flow

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.
Pre-assignment Detail	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.

Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.1 (19.1)
Sex: Female, Male (Count of Participants)
Female	3 37.5%
Male	5 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	8 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

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
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.
Time Frame	Measurements done at baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12).

Outcome Measure Data

Analysis Population Description

Completers analysis set: 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.

Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
Measure Participants	5
Change from baseline to Day 1	3
Change from baseline to Day 4	5
Change from baseline to Day 15 (week 2)	2
Change from baseline to Day 57 (week 8)	7
Change from baseline to Day 85 (week 12)	9

2. Secondary Outcome

Title	Percent Change in C-reactive Protein (CRP) From Baseline to Week 12
Description	Percent change in C-reactive protein (CRP) from baseline to Week 12 (day 85).
Time Frame	Measurements done at baseline (day -8 to -6) and week 12 (day 85).

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.

Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
Measure Participants	5
Median (Full Range) [percentage change (%)]	-79.6

3. Secondary Outcome

Title	Percent Change in Faecal Calprotectin From Baseline to Week 12
Description	Percent change in faecal calprotectin from baseline to week 12 (day 85).
Time Frame	Measurements done at baseline (day -8 to -6) and week 12 (day 85).

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.

Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
Measure Participants	5
Median (Full Range) [percentage change (%)]	13.0

4. Secondary Outcome

Title	Percent Change in Faecal Lactoferrin From Baseline to Week 12
Description	Percent change in faecal lactoferrin from baseline to week 12 (day 85).
Time Frame	Measurements done at baseline (day -8 to -6) and week 12 (day 85).

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.

Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
Measure Participants	5
Median (Full Range) [percentage change (%)]	0.4

5. Secondary Outcome

Title	Number of Participants With Clinical Remission (Defined as Mayo Score ≤2 Points, and All Subscores ≤1 Point) at Week 12
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.
Time Frame	Week 12 (day 85) following start of treatment.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
Measure Participants	5
Number (95% Confidence Interval) [Participants]	0 0%

6. Secondary Outcome

Title	Number of Patients With Drug Related Adverse Events (AEs)
Description	Number of patients with drug related adverse events (AEs) during the on-treatment period.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.

Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
Measure Participants	8
Number of patients with drug related AEs	6 75%

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
Arm/Group Title	Spesolimab 1200 mg Intravenous (i.v.)
Arm/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).
All Cause Mortality
	Spesolimab 1200 mg Intravenous (i.v.)
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Spesolimab 1200 mg Intravenous (i.v.)
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
Gastrointestinal disorders
Colitis	1/8 (12.5%)
Infections and infestations
Diverticulitis	1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	Spesolimab 1200 mg Intravenous (i.v.)
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/8 (12.5%)
Eye disorders
Conjunctival haemorrhage	1/8 (12.5%)
Eye inflammation	2/8 (25%)
Gastrointestinal disorders
Abdominal pain upper	1/8 (12.5%)
Colitis ulcerative	1/8 (12.5%)
Dyspepsia	1/8 (12.5%)
General disorders
Fatigue	1/8 (12.5%)
Infections and infestations
Gastrointestinal infection	1/8 (12.5%)
Nasopharyngitis	4/8 (50%)
Tonsillitis	1/8 (12.5%)
Investigations
Amylase increased	1/8 (12.5%)
Lipase increased	1/8 (12.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/8 (12.5%)
Back pain	1/8 (12.5%)
Musculoskeletal pain	1/8 (12.5%)
Myalgia	1/8 (12.5%)
Pain in extremity	1/8 (12.5%)
Nervous system disorders
Headache	2/8 (25%)
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)
Oropharyngeal pain	1/8 (12.5%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/8 (12.5%)
Rash macular	1/8 (12.5%)
Vascular disorders
Orthostatic hypotension	1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.