Spesolimab (BI 655130) Single Dose in Generalized Pustular Psoriasis

Study Overview
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Brief Summary
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This is a phase I, open label, single group study that is being performed to assess the safety, tolerability, Pharmacokinetics (PK) , Pharmacogenomics (PGx) and efficacy of a single dose of spesolimab in adult patients with active Generalized Pustular Psoriasis (GPP).

Official Title
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Multi-centre, Open-label, Single Arm, Phase I Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacogenomics and Efficacy of a Single Intravenous Dose of Spesolimab in Patients With Active Generalized Pustular Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Spesolimab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female patients, aged 18 to 75 years at screening, A known and documented history of Generalized Pustular Psoriasis Presenting with a flare of Generalized Pustular Psoriasis A Generalized Pustular Psoriasis Physician Global Assessment score of at least moderate severity, Generalized Pustular Psoriasis patients receiving maintenance treatment with retinoids and/or methotrexate for at least 4 weeks or Generalized Pustular Psoriasis patients not receiving any maintenance therapy, at screening, Signed and dated written informed consent prior to admission to the study, 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. A list of contraception methods meeting these criteria is provided in the patient information. Male patients must be ready and able to use condoms. - Further inclusion criteria apply Exclusion criteria: Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Immediate life-threatening flare of Generalized Pustular Psoriasis or requiring intensive care treatment, according, to the judgement of the investigator. Life-threatening complications mainly include, but are not limited to, cardiovascular/cytokine driven shock, pulmonary distress, Identified, ongoing serious/severe infection, Acute generalized exanthematous pustulosis (AEGP) Patient's clinical presentation being considered due to the differential diagnosis of toxic epidermal necrosis or Stevens-Johnson syndrome, Currently involved in or intending to participate in another investigational study during the course of this trial, Previous enrolment in this trial Use of any restricted medication, or any drug considered likely to interfere with the safe conduct of the study Background therapy with ciclosporin within the last 30 days preceding the second screening visit, Severe, progressive, or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof, as judged by the investigator. Known chronic or relevant acute infections including active tuberculosis, HIV or viral hepatitis; QuantiFERON® tuberculosis test will be performed at screening. If the result is positive, patients may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment should have been initiated and maintained according to local country guidelines. 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. Any documented active or suspected malignancy or history of malignancy within 5 years prior to second screening visit, except appropriately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix. Evidence of a current or previous disease, medical condition (including chronic alcohol or drug abuse) other than Generalized Pustular Psoriasis, surgical procedure (i.e., organ transplant), medical examination finding (including vital signs and electrocardiogram), or laboratory value at the second screening visit outside the reference range, that is in the opinion of the investigator, is clinically significant and would make the study participant unreliable to adhere to the protocol or to complete the trial, compromise the safety of the patient, or compromise the quality of the data, Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spesolimab<br> | Drug: Spesolimab<br>* Solution for infusion<br>* Other names: BI 655130;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Adverse Reactions, Defined as Drug-related Adverse Events (AE) | Percentage of patients with adverse reactions, defined as drug-related Adverse Events is presented. | Up to 140 days from the administration of spesolimab. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) Total Score at Week 2 | The GPPASI is an adaptation for Generalized Pustular Psoriasis (GPP) patients of the Psoriasis Area and Severity Index (PASI), an established measure of severity and area of psoriatic lesions in patients with psoriasis. It is a tool which provides a numeric scoring for patients overall 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 that is affected and the severity of erythema, pustules, and scaling (desquamation) over four body regions. % GPPASI change from baseline=100* (GPPASI at baseline - GPPASI at post-baseline visit)/(GPPASI at baseline). For %GPPASI change, positive numbers show reduction in GPPASI with higher values representing a larger improvement or recovery of disease, while negative numbers show an increase in GPPASI, i.e. worsening of disease. | At baseline and at Week 2. | 
| Proportion of Patients With Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Total Score of 0 (Clear) or 1 (Almost Clear) at Week 2 | GPPGA relies on clinical assessment of the GPP patient's skin presentation. It is a modified Physician Global Assessment (PGA), a physician's assessment of psoriatic lesions, which has been adapted to the evaluation of GPP patients. The investigator (or qualified site personnel) scores the erythema, pustules and scaling of all psoriatic lesions from 0 - 4. Each component is graded separately, the average is calculated and the final GPPGA is determined from this composite score. A lower score then indicates a lesser severity, with 0 being clear and 1 being almost clear. To receive a score of 0 or 1, the patient should be afebrile, in addition to skin presentation requirements. | At Week 2. | 
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Week 2 | Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale scale score at Week 2 is presented. The FACIT-Fatigue scale is a brief and reliable instrument for monitoring fatigue and its effects on patients. It is a comprehensive compilation of questions that measure health-related quality of life in patients with chronic illnesses. It comprises 13 questions, the responses to which are each recorded on a 5-point Likert scale. Scores range from 0 to 52, with lower scores representing greater fatigue, i.e. higher changes from baseline indicate higher improvement (compared to baseline) | At baseline and at Week 2. | 
| Change From Baseline in Pain Visual Analog Scale (VAS) Score at Week 2 | The pain VAS is a unidimensional measure of pain intensity. It is a continuous scale comprised of a horizontal or vertical line, usually 10 centimeters (100 millimeters (mm) in length, anchored by word descriptors at each end ('no pain', 'very severe pain'). The pain VAS is self-completed by the respondent. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the 'no pain' anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity, i.e., a negative change from baseline indicates an improvement (compared to baseline). | At baseline and at Week 2. | 
| Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Area under the concentration-time curve of spesolimab in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. | Within 1.5 hours (h) before and 0.5 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 312 h, 480 h, 648 h, 1992 h, 3336 h after spesolimab administration. | 
| Maximum Measured Concentration of Spesolimab in Plasma (Cmax) | Maximum measured concentration of spesolimab in plasma (Cmax) is reported. | Within 1.5 hours (h) before and 0.5 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 312 h, 480 h, 648 h, 1992 h, 3336 h after spesolimab administration. |