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
- Registration Number
- NCT04015518
- Lead Sponsor
- Boehringer Ingelheim
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 152
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo & Spesolimab Placebo Subcutaneous injections of placebo matching Spesolimab, with subcutaneous injections of Spesolimab starting at week 16, for a total treatment time of 52 weeks. Placebo & Spesolimab Spesolimab Subcutaneous injections of placebo matching Spesolimab, with subcutaneous injections of Spesolimab starting at week 16, for a total treatment time of 52 weeks. Spesolimab 'Speso Low' Spesolimab Subcutaneous injections of Spesolimab in a low dose scheme for a total treatment time of 52 weeks. Spesolimab 'Speso Medium-high' Spesolimab Subcutaneous injections of Spesolimab in a medium-high dose scheme for a total treatment time of 52 weeks. Spesolimab 'Speso Medium-low' Spesolimab Subcutaneous injections of Spesolimab in a medium-low dose scheme for a total treatment time of 52 weeks. Spesolimab 'Speso High' Spesolimab Subcutaneous injections of Spesolimab in a high dose scheme for a total treatment time of 52 weeks.
- Primary Outcome Measures
Name Time Method The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 16 From Baseline week 0 (baseline) and week 16 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 4 week 0 (baseline) and 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.Change From Baseline in Palmoplantar Pustulosis Pain Visual Analogue Scale (VAS) Score at Week 16 week 0 (baseline) and 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.Palmoplantar Pustulosis Severity Index (PPP SI) Change From Baseline at Week 16 week 0 (baseline) and 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.Number of Patients Achieving a 50% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI50) week 0 (baseline) and week 16 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.
Number of Patients Achieving a 75% Decrease From Baseline in Palmoplantar Pustulosis Area and Severity Index Score at Week 16 (PPP ASI75) week 0 (baseline) and week 16 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.
Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Clear/Almost Clear (0 or 1) at Week 16 week 0 (baseline) and 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.
Number of Patients With Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) Pustules Clear/Almost Clear (0 or 1) at Week 16 week 0 (baseline) and 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.
The Percentage Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) at Week 52 From Baseline week 0 (baseline) and week 52 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.
Trial Locations
- Locations (88)
Shiga University of Medical Science Hospital
🇯🇵Shiga, Otsu, Japan
Teikyo University Hospital
🇯🇵Tokyo, Itabashi-ku, Japan
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Fujita Health University Hospital
🇯🇵Aichi, Toyoake, Japan
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Nakatsu Dermatology Clinic
🇯🇵Osaka, Osaka, Japan
Fukuoka University Hospital
🇯🇵Fukuoka, Fukuoka, Japan
University of the Ryukyus Hospital
🇯🇵Okinawa, Nakagami-gun, Japan
Jichi Medical University Hospital
🇯🇵Tochigi, Shimotsuke, Japan
Nihon University Itabashi Hospital
🇯🇵Tokyo, Itabashi-ku, Japan
Asahikawa Kosei General Hospital
🇯🇵Hokkaido, Asahikawa, Japan
Takamatsu Red Cross Hospital
🇯🇵Kagawa, Takamatsu, Japan
Shinshu University Hospital
🇯🇵Nagano, Matsumoto, Japan
Independent Public Clin.Hosp.no1 Lublin
🇵🇱Lublin, Poland
Hosui General Medical Clinic
🇯🇵Hokkaido, Sapporo, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Kumamoto, Japan
Seibo Hospital
🇯🇵Tokyo, Shinjuku, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Wakayama, Japan
Amphia Ziekenhuis
🇳🇱Breda, Netherlands
Barbara Rewerska Diamond Clinic, Krakow
🇵🇱Krakow, Poland
LLC "Medical Center Azbuka Zdorovia"
🇷🇺Kazan, Russian Federation
Menter Dermatology Research Institute
🇺🇸Dallas, Texas, United States
Epiphany Dermatology of Kansas, LLC
🇺🇸Overland Park, Kansas, United States
Therapeutics Clinical Research
🇺🇸San Diego, California, United States
The Guenther Dermatology Research Centre
🇨🇦London, Ontario, Canada
Woden Dermatology
🇦🇺Phillip, Australian Capital Territory, Australia
Total Skin and Beauty Dermatology Center, PC
🇺🇸Birmingham, Alabama, United States
University of Missouri Health System
🇺🇸Columbia, Missouri, United States
UZ Leuven
🇧🇪Leuven, Belgium
Wallace Medical Group
🇺🇸Beverly Hills, California, United States
Dr. Irina Turchin PC Inc.
🇨🇦Fredericton, New Brunswick, Canada
Paddington Testing Co., Inc.
🇺🇸Philadelphia, Pennsylvania, United States
The Psoriasis Treatment Center of Central New Jersey
🇺🇸East Windsor, New Jersey, United States
Veracity Clinical Research
🇦🇺Wooloongabba, Queensland, Australia
Skin Health Institute Inc
🇦🇺Carlton, Victoria, Australia
Skin Specialists, P.C.
🇺🇸Omaha, Nebraska, United States
University of Utah Health
🇺🇸Murray, Utah, United States
Virginia Clinical Research, Inc.
🇺🇸Norfolk, Virginia, United States
Nagoya City University Hospital
🇯🇵Aichi, Nagoya, Japan
CARe Clinic
🇨🇦Red Deer, Alberta, Canada
York Dermatology Clinic and Research Centre
🇨🇦Richmond Hill, Ontario, Canada
K. Papp Clinical Research Inc.
🇨🇦Waterloo, Ontario, Canada
HOP l'Archet
🇫🇷Nice, France
HOP Larrey
🇫🇷Toulouse, France
CCBR Czech a.s.
🇨🇿Pardubice, Czechia
SimcoDerm Medical and Surgical Dermatology Centre
🇨🇦Barrie, Ontario, Canada
HOP Saint-Louis
🇫🇷Paris, France
CCBR Czech Prague s.r.o.
🇨🇿Prague 3, Czechia
Veszprem County Csolnoky Ferenc Hospital
🇭🇺Veszprem, Hungary
Tokyo Dental College Ichikawa General Hospital
🇯🇵Chiba, Ichikawa, Japan
University of Pecs
🇭🇺Pecs, Hungary
Gifu University Hospital
🇯🇵Gifu, Gifu, Japan
CRU Hungary Ltd, Private Practice, Miskolc
🇭🇺Miskolc, Hungary
Markusovszky University Teaching Hospital
🇭🇺Szombathely, Hungary
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Asahikawa Medical University Hospital
🇯🇵Hokkaido, Asahikawa, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Kyoto, Japan
Takagi Dermatological Clinic
🇯🇵Hokkaido, Obihiro, Japan
Kindai University Hospital
🇯🇵Osaka, Osaka-sayama, Japan
Shirasaki Dermatology and Neurology Clinic
🇯🇵Toyama, Takaoka, Japan
Sagamihara National Hospital
🇯🇵Kanagawa, Sagamihara, Japan
Dermoklinika medical center, Lodz
🇵🇱Lodz, Poland
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Tohoku University Hospital
🇯🇵Miyagi, Sendai, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Shinjuku-ku, Japan
Municipal Hospital Complex in Olsztyn
🇵🇱Olsztyn, Poland
Dermmedica Sp. z o.o., Wroclaw
🇵🇱Wroclaw, Poland
SBHI Chelyabinsk Reg.Clin.Derma.Dispen.
🇷🇺Chelyabinsk, Russian Federation
Dermatovenereological Dispensary #10, St. Petersburg
🇷🇺Saint-Petersburg, Russian Federation
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Universitätsklinikum Schleswig-Holstein, Campus Kiel
🇩🇪Kiel, Germany
Advanced Medical Research PC
🇺🇸Sandy Springs, Georgia, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Brussels - UNIV Saint-Luc
🇧🇪Bruxelles, Belgium
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Innovaderm Research Inc.
🇨🇦Montreal, Quebec, Canada
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Sanatorium Prof. Arenebergera
🇨🇿Prague, Czechia
Ehime University Hospital
🇯🇵Ehime, Toon, Japan
Osaka University Hospital
🇯🇵Osaka, Suita, Japan
Universitätsklinikum Frankfurt
🇩🇪Frankfurt am Main, Germany
Okayama University Hospital
🇯🇵Okayama, Okayama, Japan
Osaka City University Hospital
🇯🇵Osaka, Osaka, Japan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Guy's Hospital
🇬🇧London, United Kingdom