A Study to Test How Effective and Safe Different Doses of BI 655130 Are in Patients With a Moderate to Severe Form of the Skin Disease Palmoplantar Pustulosis

Palmoplantar Pustulosis (PPP) Clinical Trial

Official title:

Multi-center, Double-blind, Randomised, Placebo-controlled, Phase IIb Dose-finding Study to Evaluate Safety and Efficacy of Different Subcutaneous Doses of BI 655130 in Patients With Moderate to Severe Palmoplantar Pustulosis (PPP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04015518
• Other study ID #: 1368-0016
• Secondary ID: 2018-003078-28
• Status: Completed
• Phase: Phase 2
• Start date: July 31, 2019
• Est. completion date: July 28, 2021

Study information

• Verified date: June 2022
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to provide dose-ranging data for 4 dose regimens of BI 655130 compared to placebo on the primary endpoint of percentage change from baseline in PPP ASI at Week 16. The target dose(s) will be estimated from the model by incorporating information on the minimum clinically relevant effect and accounting for safety. Supportive dose-ranging assessments will also be done on pre-specified secondary endpoints.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: July 28, 2021
• Est. primary completion date: August 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18 to 75 years of legal age (according to local legislation) at screening.
• Diagnosis of Palmoplantar Pustulosis defined as presence of primary, persistent (>3 months duration), sterile, macroscopically visible pustules on the palms and/or soles, without or with plaque psoriasis elsewhere on the body.
• PPP PGA of at least moderate severity (=3) at screening and baseline.
• A minimum PPP ASI score of 12 at screening and baseline.
• Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2).
• Signed and dated written informed consent in accordance with ICH GCP and local legislation prior to admission to the trial.
• Further criteria apply.

Exclusion Criteria:

• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
• Severe, progressive, or uncontrolled condition such as renal, hepatic, haematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof.
• Presence or known history of anti-TNF-induced PPP-like disease.
• Patient with a transplanted organ (with exception of a corneal transplant >12 weeks Prior to screening) or who have ever received stem cell therapy (e.g., Prochymal).
• Known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
• Further criteria apply.

Related Conditions & MeSH terms

• Palmoplantar Pustulosis (PPP)
• Psoriasis

Intervention

Drug:
• Spesolimab
Subcutaneous injections of Spesolimab starting at week 16, for a total treatment time until week 52.
• Placebo
Subcutaneous injections of placebo matching Spesolimab from week 0 to 16.
• Spesolimab
Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks.
• Spesolimab
Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks.
• Spesolimab
Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks.
• Spesolimab
Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.

Locations

Country	Name	City	State
Australia	Skin Health Institute Inc	Carlton	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Woden Dermatology	Phillip	Australian Capital Territory
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Veracity Clinical Research	Wooloongabba	Queensland
Belgium	Brussels - UNIV Saint-Luc	Bruxelles
Belgium	UZ Leuven	Leuven
Canada	SimcoDerm Medical and Surgical Dermatology Centre	Barrie	Ontario
Canada	Dr. Irina Turchin PC Inc.	Fredericton	New Brunswick
Canada	The Guenther Dermatology Research Centre	London	Ontario
Canada	Innovaderm Research Inc.	Montreal	Quebec
Canada	CARe Clinic	Red Deer	Alberta
Canada	York Dermatology Clinic and Research Centre	Richmond Hill	Ontario
Canada	K. Papp Clinical Research Inc.	Waterloo	Ontario
Czechia	CCBR Czech a.s.	Pardubice
Czechia	Sanatorium Prof. Arenebergera	Prague
Czechia	CCBR Czech Prague s.r.o.	Prague 3
France	HOP l'Archet	Nice
France	HOP Saint-Louis	Paris
France	HOP Larrey	Toulouse
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum Frankfurt	Frankfurt am Main
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Hungary	CRU Hungary Ltd, Private Practice, Miskolc	Miskolc
Hungary	University of Pecs	Pecs
Hungary	Markusovszky University Teaching Hospital	Szombathely
Hungary	Veszprem County Csolnoky Ferenc Hospital	Veszprem
Japan	Nagoya City University Hospital	Aichi, Nagoya
Japan	Fujita Health University Hospital	Aichi, Toyoake
Japan	Tokyo Dental College Ichikawa General Hospital	Chiba, Ichikawa
Japan	Ehime University Hospital	Ehime, Toon
Japan	Fukuoka University Hospital	Fukuoka, Fukuoka
Japan	Gifu University Hospital	Gifu, Gifu
Japan	Asahikawa Kosei General Hospital	Hokkaido, Asahikawa
Japan	Asahikawa Medical University Hospital	Hokkaido, Asahikawa
Japan	Takagi Dermatological Clinic	Hokkaido, Obihiro
Japan	Hosui General Medical Clinic	Hokkaido, Sapporo
Japan	Takamatsu Red Cross Hospital	Kagawa, Takamatsu
Japan	Sagamihara National Hospital	Kanagawa, Sagamihara
Japan	Kumamoto University Hospital	Kumamoto, Kumamoto
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto, Kyoto
Japan	Tohoku University Hospital	Miyagi, Sendai
Japan	Shinshu University Hospital	Nagano, Matsumoto
Japan	Okayama University Hospital	Okayama, Okayama
Japan	University of the Ryukyus Hospital	Okinawa, Nakagami-gun
Japan	Nakatsu Dermatology Clinic	Osaka, Osaka
Japan	Osaka City University Hospital	Osaka, Osaka
Japan	Kindai University Hospital	Osaka, Osaka-sayama
Japan	Osaka University Hospital	Osaka, Suita
Japan	Shiga University of Medical Science Hospital	Shiga, Otsu
Japan	Jichi Medical University Hospital	Tochigi, Shimotsuke
Japan	Nihon University Itabashi Hospital	Tokyo, Itabashi-ku
Japan	Teikyo University Hospital	Tokyo, Itabashi-ku
Japan	Seibo Hospital	Tokyo, Shinjuku
Japan	Tokyo Medical University Hospital	Tokyo, Shinjuku-ku
Japan	Shirasaki Dermatology and Neurology Clinic	Toyama, Takaoka
Japan	Wakayama Medical University Hospital	Wakayama, Wakayama
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Amphia Ziekenhuis	Breda
Poland	Barbara Rewerska Diamond Clinic, Krakow	Krakow
Poland	Dermoklinika medical center, Lodz	Lodz
Poland	Independent Public Clin.Hosp.no1 Lublin	Lublin
Poland	Municipal Hospital Complex in Olsztyn	Olsztyn
Poland	Dermmedica Sp. z o.o., Wroclaw	Wroclaw
Russian Federation	SBHI Chelyabinsk Reg.Clin.Derma.Dispen.	Chelyabinsk
Russian Federation	LLC "Medical Center Azbuka Zdorovia"	Kazan
Russian Federation	Dermatovenereological Dispensary #10, St. Petersburg	Saint-Petersburg
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Royal Devon and Exeter Hospital	Exeter
United Kingdom	Guy's Hospital	London
United States	Wallace Medical Group	Beverly Hills	California
United States	Total Skin and Beauty Dermatology Center, PC	Birmingham	Alabama
United States	University of Missouri Health System	Columbia	Missouri
United States	Menter Dermatology Research Institute	Dallas	Texas
United States	The Psoriasis Treatment Center of Central New Jersey	East Windsor	New Jersey
United States	University of Utah Health	Murray	Utah
United States	Virginia Clinical Research, Inc.	Norfolk	Virginia
United States	Skin Specialists, P.C.	Omaha	Nebraska
United States	Epiphany Dermatology of Kansas, LLC	Overland Park	Kansas
United States	Paddington Testing Co., Inc.	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Therapeutics Clinical Research	San Diego	California
United States	Advanced Medical Research PC	Sandy Springs	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline	The percentage change in PPP ASI at Week 16 from baseline. The PPP ASI is a tool that provides a numeric scoring for patients overall PPP disease state, ranging from 0 (best) to 72 (worst). It is a linear combination of the percent of surface area of skin that is affected on the palms and soles of the body and the severity of erythema, pustules, and scaling (desquamation): The percent change from baseline is calculated as (PPP ASI current - PPP ASI baseline) / PPP ASI baseline * 100%.; Least square (LS) means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based Mixed effect model for repeated measurements (MMRM) including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used.	week 0 (baseline) and week 16
Secondary	Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4	Change from baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) score at Week 4. The PPP Pain VAS is a unidimensional measure of pain intensity due to palmoplantar pustulosis on palms and/or soles. It is a continuous scale comprised of a horizontal or vertical line, 10 centimeters (cm) in length, anchored by word descriptors at each end (score ranges from "no pain" at 0 cm to "very severe pain" at 10 cm). The patient was asked to place a vertical ( | ) mark on the horizontal line to indicate the severity of the pain.; Least square (LS) means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based MMRM including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used.	week 0 (baseline) and week 4.
Secondary	Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16	Change from baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) score at Week 16. The PPP Pain VAS is a unidimensional measure of pain intensity due to palmoplantar pustulosis on palms and/or soles. It is a continuous scale comprised of a horizontal or vertical line, 10 centimeters (cm) in length, anchored by word descriptors at each end (score ranges from "no pain" at 0 cm to "very severe pain" at 10 cm). The patient was asked to place a vertical ( | ) mark on the horizontal line to indicate the severity of the pain.; Least square (LS) means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based MMRM including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used.	week 0 (baseline) and week 16.
Secondary	Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16	PPP SI change from baseline at Week 16. The PPP SI is based on the severity score of individual components (erythema, pustules, and scaling/desquamation) of PPP ASI assessments. The most severely affected area based on pustules was identified by the investigator at baseline and assessed at all subsequent visits. The PPP SI was calculated by summing up the individual components of PPP ASI assessment (range 0 (best) to 12 (worst)) at each visit for the identified location.; Least square (LS) means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based Mixed effect model for repeated measurements (MMRM) including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used.	week 0 (baseline) and week 16.
Secondary	Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50)	Number of patients achieving a 50% decrease from baseline in Palmoplantar Pustulosis Area and Severity Index score at week 16 (PPP ASI50). The PPP ASI is an investigator assessment of the extent and severity of palmoplantar pustulosis lesions on the palms and soles in PPP patients. This tool provides a numeric scoring for patients overall PPP disease state, ranging from 0 (best) to 72 (worst). It is a linear combination of the percent of surface area of skin that is affected on the palms and soles of the body and the severity of erythema, pustules, and scaling (desquamation). When (PPP ASI baseline - PPP ASI current)/ PPP ASI baseline * 100% >= 50%, PPP ASI50 = 1.	week 0 (baseline) and week 16
Secondary	Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75)	Number of patients achieving a 75% decrease from baseline in Palmoplantar Pustulosis Area and Severity Index score at week 16 (PPP ASI75). The PPP ASI is an investigator assessment of the extent and severity of palmoplantar pustulosis lesions on the palms and soles in PPP patients. This tool provides a numeric scoring for patients overall PPP disease state, ranging from 0 (best) to 72 (worst). It is a linear combination of the percent of surface area of skin that is affected on the palms and soles of the body and the severity of erythema, pustules, and scaling (desquamation). When (PPP ASI baseline - PPP ASI current)/ PPP ASI baseline * 100% >= 75%, PPP ASI75 = 1.	week 0 (baseline) and week 16
Secondary	Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16	Number of patients with Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) clear/almost clear (0 or 1) at Week 16. The PPP PGA relies on investigator assessment of the patient's skin presentation on the palms and soles. The investigator scored the individual components (erythema, pustules, and scaling/crusting) from 0 (best) to 4 (worst) as clear, almost clear, mild, moderate or severe. PPP PGA categorization is based on the mean of the four individual components.	week 0 (baseline) and week 16
Secondary	Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16	Number of patients with Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) pustules clear/almost clear (0 or 1) at Week 16. The PPP PGA relies on investigator assessment of the patient's skin presentation on the palms and soles. The investigator scored the pustules from 0 (best) to 4 (worst) as clear, almost clear, mild, moderate or severe.	week 0 (baseline) and week 16
Secondary	The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline	The percentage change in PPP ASI at Week 52 from baseline. The PPP ASI is an investigator assessment of the extent and severity of palmoplantar pustulosis lesions on the palms and soles in PPP patients. This tool provides a numeric scoring for patients overall PPP disease state, ranging from 0 (best) to 72 (worst). It is a linear combination of the percent of surface area of skin that is affected on the palms and soles of the body and the severity of erythema, pustules, and scaling (desquamation).; LS means, differences and confidence intervals were estimated by (Restricted maximum likelihood)-based MMRM including the fixed, categorical effects of treatment at each visit, region and the continuous effect of baseline at each visit as well as random effects of subject. Values post rescue medication or 6 weeks following last study treatment before discontinuation were censored. Unstructured covariance matrix was used.	week 0 (baseline) and week 52

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