A Study to Test the Long-term Safety of BI 655130 in Patients With Atopic Eczema Who Took Part in Study 1368-0032

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04086121
• Collaborator: (none)
• Enrollment: 14
• Locations: 10
• Arm: 1
• Actual Duration (Months): 29
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To assess the long term safety and efficacy of treatment with BI 655130 in patients with AD who have completed and have responded to treatment in the parent study 1368-0032

Condition or Disease	Intervention/Treatment	Phase
Dermatitis, Atopic	Drug: Spesolimab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Extension Study to Assess the Long Term Safety of Treatment With BI 655130 Administered Subcutaneously in Adult Patients With Moderate to Severe Atopic Dermatitis
• Actual Study Start Date: Sep 24, 2019
• Actual Primary Completion Date: Apr 28, 2021
• Actual Study Completion Date: Feb 23, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Spesolimab 600 mg 600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks. All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.	Drug: Spesolimab; Solution for SC injection; Other Names: BI 655130

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Treatment Emergent Adverse Events (AEs) at Week 48 [From first dose until Week 48, up to 48 weeks.]

   Number of patients with treatment emergent adverse events (AEs) at week 48. The treatment emergent adverse event refer to the adverse event with an onset between start of treatment and end of the 16-week residual effect period after the last dose of trial medication.

Secondary Outcome Measures

1. Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 48 [At baseline and at Week 48.]

   The EASI scoring system is used routinely in patients with psoriasis to describe signs and severity of the disease. It assesses the extent of disease at four body sites and measures four clinical signs: erythema, induration/papulation, excoriation, and lichenification (each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe)). The EASI score was obtained by weight-averaging these 4 scores, resulting in the EASI score ranges from 0 (clear) to 72 (very severe), with higher score indicating more severe disease extent and clinical signs. The percent change from baseline in EASI is calculated as: (EASI at week 48 - EASI at baseline) / EASI at baseline * 100%.

2. Percentage of Patients With a 50% Improvement From Baseline in EASI (EASI50) at Week 48 [At baseline and at Week 48.]

   The EASI scoring system is used routinely in patients with psoriasis to describe signs and severity of the disease. It assesses the extent of disease at four body sites and measures four clinical signs: erythema, induration/papulation, excoriation, and lichenification (each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe)). The EASI score was obtained by weight-averaging these 4 scores, resulting in the EASI score ranges from 0 (clear) to 72 (very severe), with higher score indicating more severe disease extent and clinical signs. [(EASI at week 48 - EASI at baseline) / EASI at baseline * 100%] ≥ 50%, then EASI50 = 1.

3. Percentage of Patients With a 75% Improvement From Baseline in EASI (EASI75) at Week 48 [At baseline and at Week 48.]

   The EASI scoring system is used routinely in patients with psoriasis to describe signs and severity of the disease. It assesses the extent of disease at four body sites and measures four clinical signs: erythema, induration/papulation, excoriation, and lichenification (each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe)). The EASI score was obtained by weight-averaging these 4 scores, resulting in the EASI score ranges from 0 (clear) to 72 (very severe), with higher score indicating more severe disease extent and clinical signs. [(EASI at week 48 - EASI at baseline) / EASI at baseline * 100%] ≥ 75%, then EASI75 = 1.

4. Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 48 [At baseline and at Week 48.]

   The SCORing of Atopic Dermatitis (SCORAD) index assesses elements: extent of disease, disease severity and subjective symptoms. The SCORAD consists of three elements: extent of disease, intensity of disease, and subjective symptoms (Pruritus and Sleep Loss). These 3 aspects: extent of disease (A: score range 0-1-2), disease severity (B: score range 0-18), and subjective symptoms (C: score range 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103 for SCORAD score. The SCORAD range from 0 (no disease) to 103 (severe disease). The higher the SCORAD score, the more severe the Atopic Dermatitis is.

5. Percentage of Patients Achieving at Least a 2-grade Reduction From Baseline to Clear (0) or Almost Clear (1) in Investigator Global Assessment (IGA) at Week 48 [At baseline and at Week 48.]

   The IGA scale allows investigators to assess overall disease severity at one given time point, and it consists of a five-point severity scale from clear to very severe disease (0= clear,1 =almost clear, 2 = mild disease, 3 = moderate disease, 4= severe disease). The IGA scale uses clinical characteristics of erythema, infiltration, papulation, oozing and crusting as guidelines for the overall severity assessment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to the start of any screening procedures

• Patients who completed the 1368-0032 trial and did not prematurely discontinue treatment prior to week 16, and; In the 1368-0032 re-allocation period (V7 to V11):

• If an original non-responder from week 16 (V7), attained at least EASI 50 by last infusion (week 28) or by the EOS.

• If an original responder from week 16 (V7) completed the last visit Week 28 (EOS) or dropped to a EASI 50 score prior to Week 28.

• Women of childbearing potential (WOCBP)1 must be ready and able 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 for the duration of the trial and 16 weeks after last study drug administration. A list of contraception methods meeting these criteria is provided in the patient information.

Exclusion Criteria:

• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.

• Any new documented active or suspected malignancy except appropriately treated basal cell carcinoma, squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.

• Use of any restricted medication: or any drug considered likely to interfere with the safe conduct of the study, as assessed by the investigator.

• Active systemic infections during the last two weeks prior to first drug administration.

• Currently enrolled in another investigational device or drug trial, except for 1368-0032.

• Any condition which would prevent the patient continuing on treatment in this trial 1368-0037

• Evidence of a current or previous disease, medical condition (including chronic alcohol or drug abuse or any condition) other than AD, surgical procedure, psychiatric or social problems, medical examination finding (including vital signs and ECG), or laboratory value at the screening outside the reference range that in the opinion of the investigator is clinically significant and would make the study participant unreliable to adhere to the protocol, comply with all study visits/procedures or to complete the trial, compromise the safety of the patient or compromise the quality of the data.

• History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCT Research	Scottsdale	Arizona	United States	85260
2	Clinical Physiology Associates	Fort Myers	Florida	United States	33912
3	Finlay Medical Research Corp	Miami	Florida	United States	33126
4	ForCare Clinical Research, Inc.	Tampa	Florida	United States	33613
5	The Indiana Clinical Trials Center, PC	Plainfield	Indiana	United States	46168
6	Unity Clinical Research	Oklahoma City	Oklahoma	United States	73118
7	Dermatology Treatment and Research Center, PA	Dallas	Texas	United States	75230
8	Innovaderm Research Inc.	Montreal	Quebec	Canada	H2X 2V1
9	Tennocho Ekimae Dermatology and Allergology	Kanagawa, Yokohama		Japan	240-0004
10	Tokyo Medical University Hachioji Medical Center	Tokyo, Hachioji		Japan	193-0998

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 23, 2020
• Statistical Analysis Plan - Dec 20, 2021

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT04086121
• Other Study ID Numbers: 1368-0037
• First Posted: Sep 11, 2019
• Last Update Posted: Jul 19, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis

Study Results

Participant Flow

Recruitment Details	This open label extension clinical trial was planned to offer all patients who completed the clinical trial 1368-0032 (NCT03822832) as planned, the option to continue to receive BI 655130 treatment if they have responded to treatment and meet all criteria for study entry.
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 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks. All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
Period Title: Overall Study
STARTED	14
COMPLETED	0
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Spesolimab 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks. All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
Overall Participants	14
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.2 (14.8)
Sex: Female, Male (Count of Participants)
Female	5 35.7%
Male	9 64.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 14.3%
Not Hispanic or Latino	12 85.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 21.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 28.6%
White	7 50%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Treatment Emergent Adverse Events (AEs) at Week 48
Description	Number of patients with treatment emergent adverse events (AEs) at week 48. The treatment emergent adverse event refer to the adverse event with an onset between start of treatment and end of the 16-week residual effect period after the last dose of trial medication.
Time Frame	From first dose until Week 48, up to 48 weeks.

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF): This patient set includes all randomized patients who received at least one dose of study drug.

Arm/Group Title	Spesolimab 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks. All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
Measure Participants	14
Count of Participants [Participants]	9 64.3%

2. Secondary Outcome

Title	Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 48
Description	The EASI scoring system is used routinely in patients with psoriasis to describe signs and severity of the disease. It assesses the extent of disease at four body sites and measures four clinical signs: erythema, induration/papulation, excoriation, and lichenification (each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe)). The EASI score was obtained by weight-averaging these 4 scores, resulting in the EASI score ranges from 0 (clear) to 72 (very severe), with higher score indicating more severe disease extent and clinical signs. The percent change from baseline in EASI is calculated as: (EASI at week 48 - EASI at baseline) / EASI at baseline * 100%.
Time Frame	At baseline and at Week 48.

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): This patient set includes all patients in the SAF who had a baseline measurement and at least one post-baseline measurement for the secondary endpoint, Eczema Area and Severity Index (EASI) Total Score.

Arm/Group Title	Spesolimab 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks, up to 4 years (204 weeks) of End of Treatment (EOT). All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
Measure Participants	9
Mean (Standard Deviation) [Percent change]	-3.74 (81.99)

3. Secondary Outcome

Title	Percentage of Patients With a 50% Improvement From Baseline in EASI (EASI50) at Week 48
Description	The EASI scoring system is used routinely in patients with psoriasis to describe signs and severity of the disease. It assesses the extent of disease at four body sites and measures four clinical signs: erythema, induration/papulation, excoriation, and lichenification (each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe)). The EASI score was obtained by weight-averaging these 4 scores, resulting in the EASI score ranges from 0 (clear) to 72 (very severe), with higher score indicating more severe disease extent and clinical signs. [(EASI at week 48 - EASI at baseline) / EASI at baseline * 100%] ≥ 50%, then EASI50 = 1.
Time Frame	At baseline and at Week 48.

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): This patient set includes all patients in the SAF who had a baseline measurement and at least one post-baseline measurement for the secondary endpoint, Eczema Area and Severity Index (EASI) Total Score.

Arm/Group Title	Spesolimab 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks, up to 4 years (204 weeks) of End of Treatment (EOT). All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
Measure Participants	9
Number [Percentage of participants]	33.3 237.9%

4. Secondary Outcome

Title	Percentage of Patients With a 75% Improvement From Baseline in EASI (EASI75) at Week 48
Description	The EASI scoring system is used routinely in patients with psoriasis to describe signs and severity of the disease. It assesses the extent of disease at four body sites and measures four clinical signs: erythema, induration/papulation, excoriation, and lichenification (each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe)). The EASI score was obtained by weight-averaging these 4 scores, resulting in the EASI score ranges from 0 (clear) to 72 (very severe), with higher score indicating more severe disease extent and clinical signs. [(EASI at week 48 - EASI at baseline) / EASI at baseline * 100%] ≥ 75%, then EASI75 = 1.
Time Frame	At baseline and at Week 48.

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): This patient set includes all patients in the SAF who had a baseline measurement and at least one post-baseline measurement for the secondary endpoint, Eczema Area and Severity Index (EASI) Total Score.

Arm/Group Title	Spesolimab 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks, up to 4 years (204 weeks) of End of Treatment (EOT). All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
Measure Participants	9
Number [Percentage of participants]	22.2 158.6%

5. Secondary Outcome

Title	Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 48
Description	The SCORing of Atopic Dermatitis (SCORAD) index assesses elements: extent of disease, disease severity and subjective symptoms. The SCORAD consists of three elements: extent of disease, intensity of disease, and subjective symptoms (Pruritus and Sleep Loss). These 3 aspects: extent of disease (A: score range 0-1-2), disease severity (B: score range 0-18), and subjective symptoms (C: score range 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103 for SCORAD score. The SCORAD range from 0 (no disease) to 103 (severe disease). The higher the SCORAD score, the more severe the Atopic Dermatitis is.
Time Frame	At baseline and at Week 48.

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): This patient set includes all patients in the SAF who had a baseline measurement and at least one post-baseline measurement for the secondary endpoint, Eczema Area and Severity Index (EASI) Total Score.

Arm/Group Title	Spesolimab 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks, up to 4 years (204 weeks) of End of Treatment (EOT). All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
Measure Participants	9
Mean (Standard Deviation) [Score on a scale]	-10.07 (66.04)

6. Secondary Outcome

Title	Percentage of Patients Achieving at Least a 2-grade Reduction From Baseline to Clear (0) or Almost Clear (1) in Investigator Global Assessment (IGA) at Week 48
Description	The IGA scale allows investigators to assess overall disease severity at one given time point, and it consists of a five-point severity scale from clear to very severe disease (0= clear,1 =almost clear, 2 = mild disease, 3 = moderate disease, 4= severe disease). The IGA scale uses clinical characteristics of erythema, infiltration, papulation, oozing and crusting as guidelines for the overall severity assessment.
Time Frame	At baseline and at Week 48.

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): This patient set includes all patients in the SAF who had a baseline measurement and at least one post-baseline measurement for the secondary endpoint, Eczema Area and Severity Index (EASI) Total Score.

Arm/Group Title	Spesolimab 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks, up to 4 years (204 weeks) of End of Treatment (EOT). All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
Measure Participants	9
Number [Percentage of participants]	22.2 158.6%

Adverse Events

Time Frame	From first dose until last dose + 16 weeks, up to 765 days.
Adverse Event Reporting Description	Safety analysis set (SAF): This patient set includes all randomized patients who received at least one dose of study drug.
Arm/Group Title	Spesolimab 600 mg
Arm/Group Description	600 milligrams (mg) solution for subcutaneous (SC) injection of BI 655130 (Spesolimab) were to administered subcutaneously every 4 weeks. All patients will return 16 weeks post the last treatment for an End of Study (EOS) visit.
All Cause Mortality
	Spesolimab 600 mg
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Serious Adverse Events
	Spesolimab 600 mg
	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)
Infections and infestations
COVID-19 pneumonia	1/14 (7.1%)
Device related infection	1/14 (7.1%)
Other (Not Including Serious) Adverse Events
	Spesolimab 600 mg
	Affected / at Risk (%)	# Events
Total	11/14 (78.6%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/14 (7.1%)
Neutropenia	1/14 (7.1%)
Cardiac disorders
Atrial fibrillation	1/14 (7.1%)
Immune system disorders
Drug hypersensitivity	1/14 (7.1%)
Infections and infestations
Asymptomatic COVID-19	1/14 (7.1%)
Cellulitis	2/14 (14.3%)
Nasopharyngitis	3/14 (21.4%)
Skin infection	1/14 (7.1%)
Soft tissue infection	1/14 (7.1%)
Tinea pedis	1/14 (7.1%)
Tinea versicolour	1/14 (7.1%)
Upper respiratory tract infection	2/14 (14.3%)
Upper respiratory tract infection bacterial	1/14 (7.1%)
Urinary tract infection	1/14 (7.1%)
Injury, poisoning and procedural complications
Foot fracture	1/14 (7.1%)
Joint injury	1/14 (7.1%)
Skin laceration	1/14 (7.1%)
Splinter	1/14 (7.1%)
Investigations
Vitamin B12 decreased	1/14 (7.1%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/14 (7.1%)
Type 2 diabetes mellitus	3/14 (21.4%)
Musculoskeletal and connective tissue disorders
Arthritis	1/14 (7.1%)
Bursitis	1/14 (7.1%)
Neck pain	1/14 (7.1%)
Nervous system disorders
Cervical radiculopathy	1/14 (7.1%)
Headache	1/14 (7.1%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	4/14 (28.6%)
Dermatitis psoriasiform	1/14 (7.1%)
Diffuse alopecia	1/14 (7.1%)
Dyshidrotic eczema	1/14 (7.1%)

Limitations/Caveats

The study was terminated due to sponsor decision. The planned treatment period of 4 years was not reached.

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.