Effisayil™ 1: A Study to Test Spesolimab (BI 655130) in Patients With a Flare-up of a Skin Disease Called Generalized Pustular Psoriasis

Generalized Pustular Psoriasis Clinical Trial

Official title:

Effisayil™ 1:Multi-center, Double-blind, Randomised, Placebo-controlled, Phase II Study to Evaluate Efficacy, Safety and Tolerability of a Single Intravenous Dose of Spesolimab (BI 655130) in Patients With Generalized Pustular Psoriasis (GPP) Presenting With an Acute Flare of Moderate to Severe Intensity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03782792
• Other study ID #: 1368-0013
• Secondary ID: 2017-004231-37
• Status: Completed
• Phase: Phase 2
• Start date: January 31, 2019
• Est. completion date: January 5, 2021

Study information

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

Clinical Trial Summary

To evaluate efficacy, safety, and tolerability of spesolimab (BI 655130) compared to placebo in patients with Generalized Pustular Psoriasis (GPP) presenting with an acute flare of moderate to severe intensity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: January 5, 2021
• Est. primary completion date: September 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with GPPGA of 0 or 1 and a known and documented history of GPP per European Rare And Severe Psoriasis Expert Network (ERASPEN) criteria regardless of IL36RN mutation status, with previous evidence of fever, and/or asthenia, and/or myalgia, and/or elevated C-reactive protein, and/or leucocytosis with peripheral blood neutrophilia (above ULN) OR

-- Patients with an acute flare of moderate to severe intensity meeting the (ERASPEN) criteria of GPP with a known and documented history of GPP (per ERASPEN criteria) regardless of IL36RN mutation status, with previous evidence of fever, and/or asthenia, and/or myalgia, and/or elevated C-reactive protein, and/or leucocytosis with peripheral blood neutrophilia (above ULN)

• Male or female patients, aged 18 to 75 years at screening.

• Signed and dated written informed consent prior to admission to the study in accordance with ICH GCP and local legislation prior to start of any screening procedures.

• Women of childbearing potential 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. Note: A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal ligation is not a method of permanent sterilization. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause

• Further inclusion criteria apply

Exclusion Criteria:

• Patients with SAPHO (Synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome.

• Patients with primary erythrodermic psoriasis vulgaris.

• Patients with primary plaque psoriasis vulgaris without presence of pustules or with pustules that are restricted to psoriatic plaques.

• Drug-triggered Acute Generalized Exanthematous Pustulosis (AGEP).

• Immediate life-threatening flare of GPP or requiring intensive care treatment, according to the investigator's judgement. Life-threatening complications mainly include, but are not limited to, cardiovascular/cytokine driven shock, pulmonary distress syndrome, or renal failure.

• Severe, progressive, or uncontrolled hepatic disease, defined as >3- fold Upper Limit of Normal (ULN) elevation in AST or ALT or alkaline phosphatase, or >2-fold ULN elevation in total bilirubin.

• Further exclusion criteria apply

Related Conditions & MeSH terms

• Generalized Pustular Psoriasis
• Psoriasis

Intervention

Drug:
• Spesolimab
Solution for infusion
• Placebo
Solution for infusion

Locations

Country	Name	City	State
China	The First Hospital of Dalian Medical University	Dalian
China	2nd Affiliated Hosp Zhejiang University College of Medical	Hangzhou
China	Huashan Hospital, Fudan University	Shanghai
China	Shanghai Skin Disease Hospital	Shanghai
China	Tianjin Medical University General Hospital	Tianjin
France	HOP Saint-André	Bordeaux
France	HOP Saint-Louis	Paris
France	HOP Robert Debré	Reims
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Bonn AöR	Bonn
Germany	Universitätsklinikum Essen AöR	Essen
Germany	Klinikum der Universität München - Campus Innenstadt	München
Japan	Nagoya City University Hospital	Aichi, Nagoya
Japan	Fukuoka University Hospital	Fukuoka, Fukuoka
Japan	Asahikawa Medical University Hospital	Hokkaido, Asahikawa
Japan	Tohoku University Hospital	Miyagi, Sendai
Japan	Tokyo Medical University Hachioji Medical Center	Tokyo, Hachioji
Japan	Tokyo Medical University Hospital	Tokyo, Shinjuku-ku
Korea, Republic of	Severance Hospital	Seoul
Malaysia	Hospital Sultan Ismail	Johor Bahru
Malaysia	Hospital Sultanah Aminah	Johor Bahru
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	Hospital Pakar Sultanah Fatimah	Muar
Malaysia	Hospital Raja Permaisuri Bainun	Negeri Perak/Ipoh
Malaysia	Hospital Pulau Pinang	Pulau Pinang
Malaysia	Hospital Selayang	Selangor
Singapore	National University Hospital	Singapore
Switzerland	University Hospital of Lausanne	Lausanne
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Ramathibodi Hospital	Ratchatewi, Bangkok
Tunisia	Farhat Hached Hospital	Sousse
Tunisia	La Rabta Hospital	Tunis
Tunisia	Hedi Chaker Hospital, Department of Dermatology	Tunisia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Miami	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  China,  France,  Germany,  Japan,  Korea, Republic of,  Malaysia,  Singapore,  Switzerland,  Taiwan,  Thailand,  Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Pustulation Subscore of 0 Indicating no Visible Pustules at Week 1	The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relies on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The investigator (or qualified site personnel) scored the erythema, pustules, and scaling of all GPP lesions from 0 to 4.; The GPPGA pustulation subscore ranges from 0 to 4 where: 0 = clear; = almost clear; = mild: = moderate; = severe. A lower GPPGA pustulation subscore indicates a better outcome. A GPPGA pustulation subscore of 0 means no visible pustules.; The proportion of patients who achieved a GPPGA pustulation subscore of 0 at Week 1 is reported.	At Week 1.
Secondary	Key Secondary: Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Score of 0 or 1 at Week 1	GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score was calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each subscore was assessed using a 5 point scale score ranging from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score is assigned as follows: 0, if scores for all three subscores are 0,; 1, if 0 < mean < 1.5,; 2, if 1.5 = mean < 2.5,; 3, if 2.5 = mean < 3.5,; 4, if mean = 3.5. A lower GPPGA score indicates a better outcome, with 0 being clear and 1 being almost clear. The proportion of patients with a GPPGA score of 0 or 1 at Week 1 is reported.	At Week 1.
Secondary	Proportion of Patients With a Psoriasis Area and Severity Index for Generalized Pustular Psoriasis (GPPASI) 75 at Week 4	Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs).; A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 75 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 75% reduction.; Proportion of patients with GPPASI 75 at Week 4 is reported.	At Week 4.
Secondary	Change From Baseline in Pain Visual Analog Scale (VAS) Score at Week 4	The pain Visual Analogue Scale (VAS) is a participant-administered single-item scale designed to measure skin pain intensity from generalized pustular psoriasis (GPP) using a 100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from GPP is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (pain as bad as one can imagine).; Change from baseline was calculated by subtracting the VAS score at baseline from the VAS score at Week 4. A negative change indicates an improvement from baseline.; Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR).; NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.	Baseline and at Week 4.
Secondary	Change From Baseline in Psoriasis Symptom Scale (PSS) Score at Week 4	PSS is a 4-item patient-reported outcome instrument that assesses the severity of psoriasis symptoms in moderate to severe psoriasis patients. The symptoms included are: pain, redness, itching, and burning. The symptom severity was assessed using a 5 point scale ranging from 0 to 4 where 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe. The symptom scores are added to an unweighted total score (range: 0 to 16). A lower PSS score indicates a better outcome. Change from baseline =PSS score at Week 4 - PSS score at baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.	Baseline and at Week 4.
Secondary	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Week 4	The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Each items is scored from 0 to 4. Score range is 0 (extreme fatigue)-52 (no fatigue).; Change from baseline=FACIT Fatigue score at Week 4- FACIT-Fatigue score at baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is s (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.	Baseline and at Week 4.
Secondary	Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Score of 0 or 1 at Week 4	GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score is calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each subscore was assessed using a 5 point scale score ranging from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score is assigned as follows: 0, if scores for all three scores are 0,; 1, if 0 < mean < 1.5,; 2, if 1.5 = mean < 2.5,; 3, if 2.5 = mean < 3.5,; 4, if mean = 3.5. A lower GPPGA score indicates a better outcome, with 0 being clear and 1 being almost clear.; The proportion of participants with a GPPGA score of 0 or 1 at Week 4 is reported.	At Week 4.
Secondary	Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Pustulation Sub-score of 0 Indicating no Visible Pustules at Week 4	The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relies on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The investigator (or qualified site personnel) scores the erythema, pustules, and scaling of all GPP lesions from 0 to 4.; The GPPGA pustulation subscore ranges from 0 to 4 where: 0 = clear; = almost clear; = mild: = moderate; = severe. A lower GPPGA pustulation subscore indicates a better outcome. The proportion of patients who achieved a GPPGA pustulation subscore of 0 at Week 1 is reported.	At Week 4.
Secondary	Proportion of Patients With a Generalized Pustular Psoriasis Area and Severity Index (GPPASI) 50 at Week 4	Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs).; A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50 % reduction.; Proportion of patients with GPPASI 50 at Week 4 is reported.	At Week 4.
Secondary	Percent Change in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) From Baseline at Week 4	GPPASI provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 (no disease) to 72 (worse disease state). It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs).; %GPPASI change from baseline=(GPPASI at Week 4-GPPASI at baseline) *100/(GPPASI at baseline).; Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR).NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3. Planned statistical analysis were not performed due to lack of valid data.	Baseline and at Week 4.
Secondary	Proportion of Patients With a Generalized Pustular Psoriasis Area and Severity Index (GPPASI) 50 at Week 1	Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs).; A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50 % reduction.; Proportion of patients with GPPASI 50 at Week 1 is reported.	At Week 1.
Secondary	Percent Change in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) From Baseline at Week 1	Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs).; A higher score indicates a worse disease state, while a score of 0 indicates no disease.; The percent change from baseline at Week 1 is calculated as: % GPPASI change from baseline = (GPPASI at Week 1 - GPPASI at baseline) *100/GPPASI at baseline. If % GPPASI change from baseline is positive, it means the disease is becoming worse.	At Week 1.
Secondary	Occurrence of Treatment Emergent Adverse Events (TEAEs) up to Week 1	TEAEs were all Adverse Events (AEs) occurring between start of treatment and Day 8 (Day 8 excluded). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.; The exposure-adjusted incidence rate was calculated as: Incidence rate [1/100 patients-years] = 100 × number of patients with AE / Total AE specific time at risk [patient-years] where: Time at risk [patient-years] = (date of onset of TEAE - study drug start date + 1) /365.25	From start of treatment until Day 7, up to 7 days.
Secondary	Number of Patients With Treatment Emergent Adverse Events (TEAEs) up to Week 1	TEAEs were all Adverse Events (AEs) occurring between start of treatment and Day 8 (Day 8 excluded). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.	From start of treatment until Day 7, up to 7 days.
Secondary	Occurrence of Treatment Emergent Adverse Events (TEAEs) Within the Treatment Phase	TEAEs were all Adverse Events (AEs) occurring between start of treatment and end of the residual effect period (REP) (16 weeks). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.; The exposure-adjusted incidence rate was calculated as: Incidence rate [1/100 patients-years] = 100 × number of patients with AE / Total AE specific time at risk [patient-years] where Time at risk where: Time at risk [patient-years] = (date of onset of TEAE - study drug start date + 1) /365.25 If, for a patient, the selected TEAE did not occur then the time at risk was censored at min; Date of death; For patients who did not roll over into the Open Label Extension (OLE) study: last contact date Visit14/15; For patients who rolled over into the OLE study: the 1st dose in the OLE study; Drug stop date + 112 days; Date of Day 8 if OL spesolimab was given; Date of rescue medication if spesolimab was given.	From start of treatment until end of the residual effect period (REP) but censored at any use of open label spesolimab, up to 16 weeks.
Secondary	Number of Patients With Treatment Emergent Adverse Events (TEAEs) Within the Treatment Phase	TEAEs were all Adverse Events (AEs) occurring between start of treatment and end of the residual effect period (REP) (16 weeks). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.	From start of treatment until end of the residual effect period (REP) but censored at any use of open label spesolimab, up to 16 weeks.

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