A phase 3, randomized, double-blind, placebo-controlled, multicenter study with open-label extension to evaluate the efficacy and safety of bimekizumab in study participants with palmoplantar pustulosis

The primary objective of this phase 3 study is to evaluate the efficacy of bimekizumab compared with placebo in participants with palmoplantar pustulosis at Week 16. This evaluation addresses the therapeutic potential of interleukin-17 inhibition in this chronic inflammatory dermatosis characterized by sterile pustules on palms and soles, which significantly impairs quality of life and functional capacity.

The secondary objectives include:

• To evaluate the efficacy of bimekizumab compared with placebo on additional efficacy measures in participants with palmoplantar pustulosis.

• To evaluate the impact of bimekizumab on patient-reported outcomes in participants with palmoplantar pustulosis at Week 16.

• To assess the safety and tolerability of bimekizumab in participants with palmoplantar pustulosis from baseline through the end of the Safety Follow-up Period.

This clinical trial enrolled a total of **180 participants** diagnosed with **palmoplantar pustulosis**. The study population included both **male and female participants** aged **18 years and older**. Participants were required to have an established diagnosis of palmoplantar pustulosis for at least 24 weeks prior to enrollment. The selection criteria specified that participants must present with moderate to severe disease, defined by a **Palmoplantar Pustulosis Area Severity Index** of 12 or greater and a **Palmoplantar Pustulosis-Investigator Global Assessment** score of 3 or greater at both screening and baseline visits. Eligible participants demonstrated active disease with pustules on the palms of the hands and/or soles of the feet, characterized by pustule severity of 2 or greater in at least one region and more than 5 active white-yellow pustules across all regions. The trial population consisted of individuals who were considered appropriate candidates for systemic therapy or phototherapy. No vulnerable populations were included in this study.

This is a phase 3, randomized, double-blind, placebo-controlled, multicenter study with an open-label extension designed to evaluate the efficacy and safety of **bimekizumab** in participants with **palmoplantar pustulosis**. The study employs a **randomized** design comparing bimekizumab with **placebo**, with blinding maintained during the controlled phase. The investigational medicinal product consists of **bimekizumab** administered via **subcutaneous** injection, available in formulations of 160 mg solution for injection in pre-filled syringe and 320 mg solution for injection in pre-filled pen. A matching placebo consisting of 0.9% sodium chloride solution for injection is utilized for the control arm. The overall trial duration extends from the estimated recruitment start date in February 2026 to the estimated end date in June 2029.

Participants must be at least 18 years of age and have a confirmed diagnosis of palmoplantar pustulosis for at least 24 weeks prior to the screening visit. Key inclusion criteria require a **Palmoplantar Pustulosis Area Severity Index** (PPPASI) score of 12 or greater and a palmoplantar pustulosis-**Investigator Global Assessment** (PPP-IGA) score of 3 or greater at both screening and baseline visits. Participants must present with pustules on the palms and/or soles, defined as pustule severity of 2 or greater in at least one region and more than 5 active white-yellow pustules across all regions. Candidates must be suitable for systemic therapy or phototherapy.

The **primary endpoint** is the achievement of PPP-IGA 0/1 response at Week 16. **Secondary endpoints** include PPPASI50, PPPASI75, and PPPASI90 responses at Week 16, PPPASI50 response and PPP-IGA 0/1 response at Week 8, change from baseline in **Dermatology Life Quality Index** (DLQI) total score at Week 16, and change from baseline in **Numerical Rating Scale** (NRS) for PPP pain score in the palmoplantar areas at Week 16. Safety endpoints comprise the incidence of **treatment-emergent adverse events** (TEAEs), serious TEAEs, and TEAEs leading to permanent discontinuation of study treatment from baseline to the end of the safety follow-up period.

The study involves multiple visits throughout the trial period. The screening visit serves to assess eligibility criteria and obtain baseline measurements. The baseline visit marks the initiation of study treatment following confirmation of inclusion criteria. Follow-up visits are scheduled at Week 8 and Week 16 to evaluate efficacy and safety outcomes. An open-label extension period follows the controlled phase for eligible participants. The end-of-study visit occurs upon completion of the treatment period or at the time of early discontinuation. A safety follow-up period is implemented after the last dose of study treatment to monitor for delayed adverse events. Participant involvement extends from screening through the safety follow-up period, with the total duration dependent on completion of all study phases. Early termination from the study may occur due to withdrawal of consent, loss to follow-up, adverse events requiring discontinuation, protocol violations, investigator decision, or sponsor decision to terminate the trial.

The experimental medication utilized in this clinical trial is bimekizumab, marketed as Bimzelx, which is available in multiple formulations. The active substance bimekizumab is a protein therapeutic classified under ATC code L04AC21. The investigational medicinal product is supplied in two dosage strengths: 160 mg and 320 mg. The 160 mg strength is provided as a solution for injection in a pre-filled syringe, while the 320 mg strength is available as a solution for injection in a pre-filled pen. The 160 mg formulation is contained in a one milliliter Type I glass pre-filled syringe equipped with a fluoropolymer-laminated bromobutyl rubber stopper, a staked 27-gauge, half-inch thin wall needle, and a rigid needle shield consisting of a thermoplastic elastomer needle cover and a polypropylene rigid shield assembled in an automatic needle guard. The 320 mg formulation is contained in a two milliliter pre-filled pen containing a pre-filled syringe with identical technical specifications as the 160 mg syringe formulation. All formulations of bimekizumab are administered via the subcutaneous route. The investigational medicinal product undergoes manufacturing activities outside of the scope of the approved license application, including clinical secondary packaging and labeling. The maximum treatment period is specified as one year.

The trial incorporates a placebo comparator to enable double-blind assessment of treatment efficacy. The placebo is described as matching test formulation consisting of 0.9% sodium chloride solution for injection, which is an unauthorized medicinal product specifically prepared for use in this clinical trial. The placebo is designed to match the appearance and administration characteristics of the active investigational medicinal product to maintain blinding integrity throughout the study.

Efficacy will be assessed using the Palmoplantar Pustulosis-Investigator Global Assessment (PPP-IGA) and the Palmoplantar Pustulosis Area Severity Index (PPPASI). The primary endpoint is the achievement of PPP-IGA 0/1 response at Week 16. Secondary efficacy endpoints include PPPASI50, PPPASI75, and PPPASI90 responses at Week 16, as well as PPPASI50 and PPP-IGA 0/1 responses at Week 8. Additional secondary endpoints comprise the change from Baseline in Dermatology Life Quality Index (DLQI) total score at Week 16 and the change from Baseline in Numerical Rating Scale (NRS) for PPP Pain score in the palmoplantar areas at Week 16. Safety assessments will include the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to permanent discontinuation of study treatment from Baseline to the end of the Safety Follow-up Period.