Back to resultsEffisayil™ 1: A Study to Test Spesolimab (BI 655130) in Patients With a Flare-up of a Skin Disease Called Generalized Pustular Psoriasis
Primary Purpose
Generalized Pustular Psoriasis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Spesolimab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Generalized Pustular Psoriasis
Eligibility Criteria
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
Sites / Locations
- University of Alabama at Birmingham
- University of Miami
- University of South Florida
- Icahn School of Medicine at Mount Sinai
- The First Hospital of Dalian Medical University
- 2nd Affiliated Hosp Zhejiang University College of Medical
- Shanghai Skin Disease Hospital
- Huashan Hospital, Fudan University
- Tianjin Medical University General Hospital
- HOP Saint-André
- HOP Saint-Louis
- HOP Robert Debré
- Charité - Universitätsmedizin Berlin
- Universitätsklinikum Bonn AöR
- Universitätsklinikum Essen AöR
- Klinikum der Universität München - Campus Innenstadt
- Nagoya City University Hospital
- Fukuoka University Hospital
- Asahikawa Medical University Hospital
- Tohoku University Hospital
- Tokyo Medical University Hachioji Medical Center
- Tokyo Medical University Hospital
- Severance Hospital
- Hospital Sultanah Aminah
- Hospital Sultan Ismail
- Hospital Kuala Lumpur
- Hospital Pakar Sultanah Fatimah
- Hospital Raja Permaisuri Bainun
- Hospital Pulau Pinang
- Hospital Selayang
- National University Hospital
- University Hospital of Lausanne
- National Taiwan University Hospital
- Ramathibodi Hospital
- Farhat Hached Hospital
- Hedi Chaker Hospital, Department of Dermatology
- La Rabta Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Spesolimab
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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'.
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.
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'.
Full Information
NCT ID
NCT03782792
First Posted
December 19, 2018
Last Updated
February 11, 2022
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT03782792
Brief Title
Effisayil™ 1: A Study to Test Spesolimab (BI 655130) in Patients With a Flare-up of a Skin Disease Called Generalized Pustular Psoriasis
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 31, 2019 (Actual)
Primary Completion Date
September 23, 2020 (Actual)
Study Completion Date
January 5, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Generalized Pustular Psoriasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Spesolimab
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Spesolimab
Other Intervention Name(s)
BI 655130
Intervention Description
Solution for infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Solution for infusion
Primary Outcome Measure Information:
Title
Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Pustulation Subscore of 0 Indicating no Visible Pustules at Week 1
Description
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.
Time Frame
At Week 1.
Secondary Outcome Measure Information:
Title
Key Secondary: Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Score of 0 or 1 at Week 1
Description
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.
Time Frame
At Week 1.
Title
Proportion of Patients With a Psoriasis Area and Severity Index for Generalized Pustular Psoriasis (GPPASI) 75 at Week 4
Description
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.
Time Frame
At Week 4.
Title
Change From Baseline in Pain Visual Analog Scale (VAS) Score at Week 4
Description
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.
Time Frame
Baseline and at Week 4.
Title
Change From Baseline in Psoriasis Symptom Scale (PSS) Score at Week 4
Description
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.
Time Frame
Baseline and at Week 4.
Title
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Week 4
Description
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.
Time Frame
Baseline and at Week 4.
Title
Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Score of 0 or 1 at Week 4
Description
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.
Time Frame
At Week 4.
Title
Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Pustulation Sub-score of 0 Indicating no Visible Pustules at Week 4
Description
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.
Time Frame
At Week 4.
Title
Proportion of Patients With a Generalized Pustular Psoriasis Area and Severity Index (GPPASI) 50 at Week 4
Description
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.
Time Frame
At Week 4.
Title
Percent Change in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) From Baseline at Week 4
Description
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.
Time Frame
Baseline and at Week 4.
Title
Proportion of Patients With a Generalized Pustular Psoriasis Area and Severity Index (GPPASI) 50 at Week 1
Description
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.
Time Frame
At Week 1.
Title
Percent Change in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) From Baseline at Week 1
Description
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.
Time Frame
At Week 1.
Title
Occurrence of Treatment Emergent Adverse Events (TEAEs) up to Week 1
Description
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
Time Frame
From start of treatment until Day 7, up to 7 days.
Title
Number of Patients With Treatment Emergent Adverse Events (TEAEs) up to Week 1
Description
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'.
Time Frame
From start of treatment until Day 7, up to 7 days.
Title
Occurrence of Treatment Emergent Adverse Events (TEAEs) Within the Treatment Phase
Description
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.
Time Frame
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.
Title
Number of Patients With Treatment Emergent Adverse Events (TEAEs) Within the Treatment Phase
Description
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'.
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
The First Hospital of Dalian Medical University
City
Dalian
ZIP/Postal Code
116011
Country
China
Facility Name
2nd Affiliated Hosp Zhejiang University College of Medical
City
Hangzhou
ZIP/Postal Code
310009
Country
China
Facility Name
Shanghai Skin Disease Hospital
City
Shanghai
ZIP/Postal Code
200000
Country
China
Facility Name
Huashan Hospital, Fudan University
City
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Tianjin Medical University General Hospital
City
Tianjin
ZIP/Postal Code
30052
Country
China
Facility Name
HOP Saint-André
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
HOP Saint-Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
HOP Robert Debré
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum Bonn AöR
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitätsklinikum Essen AöR
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Klinikum der Universität München - Campus Innenstadt
City
München
ZIP/Postal Code
80337
Country
Germany
Facility Name
Nagoya City University Hospital
City
Aichi, Nagoya
ZIP/Postal Code
467-8602
Country
Japan
Facility Name
Fukuoka University Hospital
City
Fukuoka, Fukuoka
ZIP/Postal Code
814-0180
Country
Japan
Facility Name
Asahikawa Medical University Hospital
City
Hokkaido, Asahikawa
ZIP/Postal Code
078-8510
Country
Japan
Facility Name
Tohoku University Hospital
City
Miyagi, Sendai
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Tokyo Medical University Hachioji Medical Center
City
Tokyo, Hachioji
ZIP/Postal Code
193-0998
Country
Japan
Facility Name
Tokyo Medical University Hospital
City
Tokyo, Shinjuku-ku
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Severance Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Hospital Sultanah Aminah
City
Johor Bahru
ZIP/Postal Code
80100
Country
Malaysia
Facility Name
Hospital Sultan Ismail
City
Johor Bahru
ZIP/Postal Code
81100
Country
Malaysia
Facility Name
Hospital Kuala Lumpur
City
Kuala Lumpur
ZIP/Postal Code
50586
Country
Malaysia
Facility Name
Hospital Pakar Sultanah Fatimah
City
Muar
ZIP/Postal Code
84000
Country
Malaysia
Facility Name
Hospital Raja Permaisuri Bainun
City
Negeri Perak/Ipoh
ZIP/Postal Code
30450
Country
Malaysia
Facility Name
Hospital Pulau Pinang
City
Pulau Pinang
ZIP/Postal Code
10990
Country
Malaysia
Facility Name
Hospital Selayang
City
Selangor
ZIP/Postal Code
68100
Country
Malaysia
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Facility Name
University Hospital of Lausanne
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10016
Country
Taiwan
Facility Name
Ramathibodi Hospital
City
Ratchatewi, Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Farhat Hached Hospital
City
Sousse
ZIP/Postal Code
4000
Country
Tunisia
Facility Name
Hedi Chaker Hospital, Department of Dermatology
City
Tunisia
ZIP/Postal Code
1053
Country
Tunisia
Facility Name
La Rabta Hospital
City
Tunis
ZIP/Postal Code
1007
Country
Tunisia
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
The data shared are the raw clinical study data sets.
IPD Sharing Time Frame
After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
IPD Sharing Access Criteria
For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
IPD Sharing URL
https://www.mystudywindow.com/msw/datasharing
Citations:
PubMed Identifier
34936739
Citation
Bachelez H, Choon SE, Marrakchi S, Burden AD, Tsai TF, Morita A, Navarini AA, Zheng M, Xu J, Turki H, Anadkat MJ, Rajeswari S, Hua H, Vulcu SD, Hall D, Tetzlaff K, Thoma C, Lebwohl MG; Effisayil 1 Trial Investigators. Trial of Spesolimab for Generalized Pustular Psoriasis. N Engl J Med. 2021 Dec 23;385(26):2431-2440. doi: 10.1056/NEJMoa2111563.
Results Reference
derived
PubMed Identifier
33785490
Citation
Choon SE, Lebwohl MG, Marrakchi S, Burden AD, Tsai TF, Morita A, Navarini AA, Zheng M, Xu J, Turki H, Rajeswari S, Deng H, Tetzlaff K, Thoma C, Bachelez H. Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare. BMJ Open. 2021 Mar 30;11(3):e043666. doi: 10.1136/bmjopen-2020-043666.
Results Reference
derived
Links:
URL
http://www.mystudywindow.com
Description
Related Info
Learn more about this trial
Effisayil™ 1: A Study to Test Spesolimab (BI 655130) in Patients With a Flare-up of a Skin Disease Called Generalized Pustular Psoriasis
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