Phase 2 Multicenter Open-Label Study of Sonelokimab in Moderate-to-Severe Palmoplantar Pustulosis Patients

Trial ID: 2024-513305-32-00
Protocol: M1095-PPP-201
Sponsor: MoonLake Immunotherapeutics AG

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Diseases & Conditions

Palmoplantar pustulosis

Objectives

The primary objective of this Phase 2, multicentre, open-label study is to demonstrate the **efficacy** of **sonelokimab** in patients with moderate-to-severe **palmoplantar pustulosis**. The study aims to assess the improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 16 compared with baseline. This is clinically relevant as it evaluates the potential of sonelokimab to provide therapeutic benefits in reducing the severity and extent of lesions in this patient population, which can significantly impact their quality of life.

Participants

The clinical trial involves participants diagnosed with **Palmoplantar Pustulosis** (PPP), specifically those with a history of the disease for at least six months and classified as having moderate-to-severe PPP. The study population includes both male and female subjects, aged 18 years and older, who are eligible for systemic therapy due to inadequate control of PPP with topical treatments, phototherapy, or previous systemic therapies. Participants must not be pregnant or breastfeeding, and women of childbearing potential are required to use highly effective contraception methods during the study and for a specified period after the last dose. Male participants must agree to use condoms when sexually active with partners of childbearing potential. The trial includes a vulnerable population, and participants must be capable of providing informed consent and comply with study requirements. The sponsor has not provided the total number of participants involved in the trial.

Plans and Procedures

The clinical trial is a **Phase 2**, multicentre, open-label study designed to evaluate the efficacy of **sonelokimab** in patients with moderate-to-severe **palmoplantar pustulosis**. The primary objective is to assess the improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 16 compared to baseline. The trial is expected to commence recruitment on September 16, 2024, and conclude by February 28, 2026. Participants will receive **sonelokimab** via subcutaneous injection, with a maximum daily dose of 120 mg/ml and a total dose not exceeding 720 mg/ml over a 12-week treatment period.

Participants must be at least 18 years old, have a history of the disease for at least six months, and meet specific criteria regarding the severity of their condition. Female participants must not be pregnant or breastfeeding and must adhere to effective contraception methods. Male participants are required to use condoms during the study and for eight weeks after the last dose. The study involves several visits, starting with a screening visit to confirm eligibility, followed by regular follow-up visits to monitor progress and safety, and concluding with an end-of-study visit to assess the final outcomes.

The expected duration of participant involvement is approximately 16 weeks, including the treatment and follow-up periods. Participants may be withdrawn from the study if they fail to comply with the protocol, experience adverse effects, or choose to discontinue participation. The study aims to provide valuable insights into the treatment of **palmoplantar pustulosis** with **sonelokimab**, contributing to the understanding of its therapeutic potential in this patient population.

Treatment

The clinical trial involves the administration of **Sonelokimab**, an experimental medication developed by Moonlake Immunotherapeutics AG. Sonelokimab is formulated as an **injection** and is classified as a protein of other origin. The medication is administered via **subcutaneous injection**. The dosing regimen for Sonelokimab includes a maximum daily dose of 120 mg/ml and a maximum total dose of 720 mg/ml over the course of the treatment period. The treatment duration is set for a maximum of 12 weeks. The study aims to evaluate the efficacy of Sonelokimab in improving the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) in participants with moderate-to-severe pustulosis palmoplantaris.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the effects of Sonelokimab. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The trial is designed to provide insights into the therapeutic potential of Sonelokimab in the specified patient population.

Efficacy

Efficacy in this clinical trial will be assessed by evaluating the improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (**PPPASI**) at Week 16 compared with baseline. The primary endpoint is the percent change from baseline in the **PPPASI** score at Week 16. This assessment will be conducted in participants with moderate-to-severe Palmoplantar Pustulosis (PPP) who are inadequately controlled by topical treatment, phototherapy, or previous systemic therapy.

The trial is designed as a Phase 2, multicentre, open-label study to explore the effects of Sonelokimab, administered via subcutaneous injection. The efficacy parameters will be collected and analyzed at specified timepoints, with the primary focus on the change in **PPPASI** score from baseline to Week 16. The study aims to demonstrate the efficacy of Sonelokimab in improving the severity of PPP in the target population.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Participants must be ≥18 years of age at the time of signing the informed consent.
Participants with PPP (disease history of at least 6 months of diagnosis), who are eligible for treatment with systemic therapy defined as having PPP inadequately controlled by topical treatment and/or phototherapy and/or previous systemic therapy.
Participants with moderate-to-severe PPP defined as a PPPASI ≥12 with or without concomitant plaque-type psoriasis.
Female participants are eligible to participate if they are not pregnant or breastfeeding and must be of non-childbearing potential or (if a woman of childbearing potential [WOCBP]) must agree to use highly effective methods of contraception during the study and for at least 8 weeks after the last dose of study treatment. WOCBP must have a negative urine pregnancy test at screening and a negative urine pregnancy test at Week 0/Day 1 before initiation of study treatment. See Appendix 4: Contraceptive and Barrier Guidance for the definition of non-childbearing potential, childbearing potential, and highly effective methods of contraception.
Male participants must be willing to use a condom when sexually active with a partner of childbearing potential during the study and for at least 8 weeks after the last dose of study treatment, unless surgically sterile.
Participants must be capable of giving signed informed consent as described in Appendix 1: Regulatory, Ethical, and Study Oversight Considerations, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Participants must complete at least 4 out of 7 days of electronic diary (eDiary) entries in at least 1 of the 2 weeks before baseline.

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Exclusion Criteria

Participants with a known hypersensitivity to sonelokimab or any of its excipients.
Participants with any other active skin disease or condition that may, in the opinion of the investigator, interfere with the assessment of PPP.
Participants with pustular psoriasis lesions on a part of the body other than hands or feet.
Participants with underlying conditions (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, or cardiac) that, in the investigator’s opinion, potentially places the participant at unacceptable risk.
Participants with current severe or uncontrolled disease(s) that put(s) the participant at increased risk, including any medical or psychiatric condition that, in the investigator’s opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.
Participants with any other known autoimmune disease or any medical condition that in the investigator’s opinion would interfere with an accurate assessment of the clinical symptoms of PPP, prevent participants from complying with protocol requirements (including the requirement for prohibited medications), or put the participant at undue risk.
Participants with a gastrointestinal condition including inflammatory bowel disease or diagnosis of ulcerative colitis or Crohn’s disease.
Participants who have experienced a period of ≥3 weeks of unexplained diarrhea in the 24 weeks before the initiation of study treatment.
Participants with an active infection or history of infections, including any of the following: a. Any infection (exception: common cold) requiring systemic anti-infective treatment within 14 days before initiation of study treatment. b. Serious infection, defined as requiring hospitalization or intravenous antiinfectives, within 2 months before initiation of study treatment. c. Candida infection requiring systemic therapy for ≥7 days in the last 12 months before initiation of study treatment. d. Previous esophageal or systemic candidiasis. e. Current active candidiasis or Candida infection within the last 3 months before the initiation of study treatment.
Participants with evidence of TB infection (active, history of active, or latent) at the Screening Visit.
Participants with any current non-tuberculous mycobacterial infection or any history of pulmonary non-tuberculous mycobacterial infection at the Screening Visit.
Participants with a concurrent acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the Screening Visit.
Participants with evidence of HIV infection at the Screening Visit.
Participants with a concurrent malignancy or a history of malignancy within 5 years of the initiation of study treatment with the following exceptions: a. Three or fewer successfully excised or ablated basal cell carcinomas of the skin.MoonLake Immunotherapeutics AG 21 May 2024 Protocol M1095-PPP-201 Final Version 1.0 CONFIDENTIAL Page 28 of 90 b. One squamous cell carcinoma of the skin not worse than Stage T1 that has been successfully treated, with no signs of recurrence or metastases for at least the past 2 years before study treatment initiation. c. Actinic keratosis. d. Squamous cell carcinoma in situ (other than actinic keratosis) of the skin successfully treated >6 months before study treatment initiation. e. Localized carcinoma in situ of the cervix treated and considered cured
Participants with a history of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
Participants with primary immunodeficiencies, prior splenectomy, or suppressive conditions, including participants taking immunosuppressive therapy following organ transplants.
Participants who currently use or plan to use one or more prohibited treatments specified in this protocol.
Participants who are receiving any glucagon-like peptide-1 (GLP1) agonist (e.g., semaglutide) or gastric inhibitory polypeptide (GIP)/GLP1 agonist (e.g., tirzepatide) for less than 24 weeks before the initiation of study treatment.
Participants who have used topical therapy as follows: a. Topical treatment within 14 days of baseline, including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, topical calcineurin inhibitors, retinoids, tazarotene, as well as emollients and other nonprescription topical products that contain urea, >3% salicylic acid, or alpha- or beta-hydroxy acids, and medicated shampoos (e.g., those that contain >3% salicylic acid, corticosteroids, coal tar, or vitamin D3 analogues). b. Bland emollients (without alpha or beta hydroxy acids) within 24 hours of the Baseline Visit. Note that bland emollients (without alpha- or beta-hydroxy acids) may be used during the study, but MAY NOT be used within 24 hours prior to any study visit.
Participants who have used the following within 28 days of baseline: ultraviolet A light therapy (with or without psoralen); ultraviolet B light therapy; excimer laser; oral retinoids; methotrexate; cyclosporine; systemically administered calcineurin inhibitors; azathioprine; thioguanine; hydroxyurea; cyclophosphamide; fumarates; apremilast; Janus kinase (JAK) inhibitors; or oral or parenteral corticosteroids including intramuscular or intraarticular administration (exception: otic, nasal, ophthalmic, or inhaled corticosteroids within recommended doses are permitted); other non-biologic systemic therapy for psoriasis.
Participants who are not willing to limit ultraviolet light exposure (e.g., sunbathing and/or the use of tanning devices) during the study.
Participants who have received live (including attenuated) vaccination within 8 weeks of baseline.
Participants with previous exposure to anti-IL-17RA (e.g., brodalumab), and/or antiIL-17A/F therapies (e.g., bimekizumab), including sonelokimab.
Participants who are unsuitable for IL-17A therapy according to the investigator’s discretion (e.g., documented primary non-responder within 16 weeks to previous therapy or AEs leading to discontinuation with secukinumab and/or ixekizumab).
Participants with prior exposure to >2 biologic response modifiers (even if within the same drug class).
Participants who have received immunomodulatory biologic therapies, (e.g., anakinra, abatacept, belimumab, tocilizumab, efalizumab) in the 12 weeks prior to baseline.
Participants who have received secukinumab, ixekizumab, or anti-TNF alpha (α) therapies within 12 weeks prior to baseline; ustekinumab, IL-23p19 targeting therapies, or any other investigational biological therapy within 6 months prior to baseline; or 5 half-lives of baseline, whichever is the longer.
Participants who have received rituximab (including biosimilars) in the 2 years prior to baseline.
Participants who are enrolled in another interventional investigational study for a device or drug or have been so enrolled in the last 28 days before the initiation of study treatment or within 5 half-lives of the investigational study drug before the initiation of study treatment, whichever is longer.
Participants with laboratory abnormalities at the Screening Visit, including any of the following: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) >3× upper limit of normal (ULN). b. Serum direct bilirubin >1.5×ULN (in the absence of known Gilbert syndrome). c. White blood cell count <3.0×109/L. d. Absolute neutrophil count <1.5×109/L. e. Absolute lymphocyte count <0.7×109/L. f. Platelet count <100×109/L. g. Hemoglobin <85 g/L. h. Creatinine clearance <30 mL/min (by Cockcroft Gault formula).
Participants with any other laboratory abnormality which, in the investigator’s opinion, might compromise participant’s safety, prevent the participant from completing the study, or would interfere with the interpretation of the study results.
Participants who have had major surgery (e.g., hip replacement, aneurysm removal) within 6 months before the initiation of study treatment or are planning to have major surgery during the study.
Participants with the presence of active suicidal ideation or positive suicidal behavior, defined as any of the following:MoonLake Immunotherapeutics AG 21 May 2024 Protocol M1095-PPP-201 Final Version 1.0 CONFIDENTIAL Page 30 of 90 a. Participants with any history of suicidal attempt (including an actual attempt, interrupted attempt, or aborted attempt) irrespective of response using the Columbia-Suicide Severity Rating Scale (C-SSRS). b. Participants with suicidal ideation in the past 6 months as indicated by a positive response to either Question 4 or 5 of the C-SSRS at the Screening Visit. c. Participants with positive suicidal behavior (as indicated by the C-SSRS) at the Screening Visit. d. Participants with active suicidal ideation (as indicated by a positive response to either Question 4 or 5 of the C-SSRS) or positive suicidal behavior (as indicated by the C-SSRS) at the Baseline Visit.
Participants with presence of moderate depression, indicated by a score of ≥10 using the screening Patient Health Questionnaire (PHQ-9). Medication used to treat depression should be stable for 8 weeks before initiation of study treatment.
Participants who have a history of chronic alcohol or drug abuse in the past year before the Screening Visit.
Participants who are an employee or a direct relative of an employee of the sponsor, a study center, or a third-party organization involved in the study.
For participants with skin biopsy samples taken, clinically relevant coagulation disorders or medication or known hypersensitivity against local anesthetics.