Long-term Safety and Efficacy Evaluation of Spesolimab in Patients with Generalized Pustular Psoriasis Following Prior Spesolimab Trials

Trial ID: 2023-509216-28-00
Protocol: 1368-0025
Sponsor: Leo Pharma A/S

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Diseases & Conditions

Pustular psoriasis

Objectives

The primary objective of this study is to evaluate the long-term **safety** and **efficacy** of **spesolimab** in patients with Generalized Pustular Psoriasis (GPP) who have completed previous spesolimab trials and are qualified for entry in this trial. This is clinically relevant as it aims to provide insights into the sustained therapeutic benefits and potential adverse effects of spesolimab over an extended period, which is crucial for the management of GPP, a rare and severe form of psoriasis characterized by widespread pustules and systemic inflammation.

Participants

The clinical trial involves a total of **108 participants** who have been diagnosed with **Generalized Pustular Psoriasis** (GPP). The study population includes both male and female subjects, encompassing a broad age range, specifically categories 2, 3, and 4, which typically represent children, adolescents, and adults. Participants were selected based on their completion of previous spesolimab trials (1368-0013 or 1368-0027) without premature discontinuation and their willingness to continue treatment in the current trial. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. Participants are required to have signed and dated written informed consent and assent in accordance with ICH-GCP and local legislation. Women of childbearing potential must adhere to highly effective birth control methods to minimize the risk of pregnancy during the trial. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The primary objective is to evaluate the long-term safety and efficacy of spesolimab in this specific patient population.

Plans and Procedures

The clinical trial is designed to evaluate the long-term safety and efficacy of **spesolimab** in patients with **Generalized Pustular Psoriasis** (GPP) who have completed previous spesolimab trials. This is a Phase 4, open-label, long-term extension study. The trial employs a non-randomized, open-label design, allowing all eligible participants to receive the investigational product. The study is expected to last until January 2028, with participant involvement extending up to 252 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as completion of prior spesolimab trials without premature discontinuation and the ability to provide informed consent. Women of childbearing potential must adhere to strict contraceptive measures. The primary endpoint is the occurrence of treatment-emergent adverse events (TEAEs) up to week 252. Secondary endpoints include the reoccurrence of a GPP flare, time to achieve a GPPGA score of 0 or 1, and changes in the Psoriasis Symptom Scale (PSS) score.

Study visits will be scheduled at regular intervals to monitor safety and efficacy outcomes. Follow-up visits will assess the presence of adverse events, disease flare-ups, and response to treatment. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any necessary post-study care is arranged. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or choose to withdraw consent.

Treatment

The clinical trial involves the administration of **spesolimab**, a biologically derived medication, to evaluate its long-term safety and efficacy in patients with Generalized Pustular Psoriasis (GPP). The experimental medication is provided in two pharmaceutical forms. The first form is a **solution for infusion**, identified by the sponsor product code BI 655130. This form is administered intravenously. The maximum daily dose for this form is 900 mg, with a total maximum dose of 1800 mg over a treatment period of up to 252 days. The solution for infusion is manufactured by Boehringer Ingelheim International and is not a pediatric formulation.

The second form of **spesolimab** is a **solution for injection in a pre-filled syringe**, also identified by the sponsor product code BI 655130. This form is administered subcutaneously. The maximum daily dose for this form is 300 mg, with a total maximum dose of 19200 mg over the same treatment period of 252 days. Like the infusion form, this solution is also produced by Boehringer Ingelheim International and is not intended for pediatric use. Both forms of spesolimab are of biological origin, specifically a protein classified as "Protein - Other".

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The trial is designed to include patients who have completed previous spesolimab trials and are qualified for entry into this long-term extension study.

Efficacy

The efficacy of spesolimab in patients with **Generalized Pustular Psoriasis (GPP)** will be assessed through several secondary endpoints. These include the reoccurrence of a GPP flare as defined by the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA), the time to first achievement of a GPPGA score of 0 or 1 in patients who received flare rescue treatment, and a GPPGA pustulation sub-score of 0 indicating no visible pustules, by visit in patients who received flare rescue treatment. Additionally, changes from baseline in the Psoriasis Symptom Scale (PSS) score will be evaluated by visit in patients who received flare rescue treatment.

The collection and analysis of these efficacy parameters will be conducted at specified visits throughout the trial. The GPPGA and PSS are validated scales used to measure the severity and symptoms of GPP, providing a standardized method for assessing patient outcomes. The trial is designed to monitor these parameters over a long-term period, with the estimated end date set for January 20, 2028. This approach ensures a comprehensive evaluation of the long-term efficacy of spesolimab in managing GPP symptoms and preventing flare-ups.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or female patients who have completed the treatment period without premature discontinuation in the previous spesolimab trial (1368-0013 or 1368-0027) and are willing and able to continue treatment in the current trial
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, parent(s) (or patient’s legal guardian) information. 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.
Signed and dated written informed consent and assent for the current trial 1368-0025, in accordance with ICH-GCP and local legislation prior to admission to the current trial

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Exclusion Criteria

Evidence of flare symptoms of moderate/severe intensity at screening
Treatment with any restricted medication, or any drugs considered by the investigator likely to interfere with the safe conduct of the study since the last visit of the previous spesolimab trial and during the screening period for the current trial, with the exception of methotrexate, cyclosporine, or retinoids started following rescue treatment for GPP flare in trial 1368-0027.
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.
Patients with congestive heart disease, as assessed by the investigator.
Relevant chronic or acute infections including human immunodeficiency virus (HIV) or viral hepatitis. A patient can be re-screened if the patient was treated and is cured from acute infection.
Active or Latent tuberculosis (TB): - Patients with active tuberculosis should be excluded - Patients will be screened with Interferon Gamma Release Assay (IGRA) such as QuantiFERON®-TB-Gold Plus or T-spot®. Patients with positive IGRA (indicating active or latent tuberculosis) are excluded unless they have completed treatment for active or latent tuberculosis per investigator discretion, at the time of screening. - Patients with indeterminate QuantiFERON®-TB-Gold Plus or invalid/borderline T-spot® may be retested with IGRA (once) or Tuberculin Skin test (TST). - TST or any alternative test/procedure (as per local standards) to rule out TB can be performed if IGRA is not available or indeterminate. A TST reaction ≥10mm (≥5mm if receiving ≥15mg/d prednisone or other immunosuppressant) is considered positive. Patients with a positive TST are excluded unless they have completed treatment as above.
History of allergy/hypersensitivity to a systemically administered trial medication agent or its excipients.
Further criteria apply.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	27 May 2019	1
France	Not Recruiting	27 May 2019	10
Germany	Not Recruiting	27 May 2019	12
Italy	Not Recruiting	27 May 2019	1
Spain	Not Recruiting	27 May 2019	1