A Study to Evaluate ABY-035 in Subjects With Moderate-to-severe Plaque Psoriasis (AFFIRM-35)

A Phase II, Randomized, Parallel Group, Placebo-controlled, Double-blinded, Dose-finding Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of ABY-035 in Subjects With Moderate-to-severe Plaque Psoriasis

This randomized, double-blinded dose-finding study evaluates four dose levels of ABY-035, in comparison to placebo, in subjects with moderate to severe plaque psoriasis. The study consists of 52-week Core study and two optional 52-week periods, Extension and Prolongation of Extension. The Core study consists of three periods: Induction (placebo-controlled, Week 0-12), Optimization (Week 12-24), and Individualization (Week 24-52).

The Core study evaluates four doses of ABY-035, in comparison to placebo, in subjects with moderate to severe plaque psoriasis. The treatment periods in the Core study are: Induction (Week 0-12) - four dose levels and placebo (Q2W) Optimization (Week 12-24) - starting with a possible dose adjustment (all subjects on Q2W) depending on PASI score. Subjects on placebo switch to active drug (Q4W). Individualization (Week 24-52) - starting with a switch to Q4W for all subjects. From week 32 dosing interval alters depending on PASI score. The study is unblinded after completion of the Core study. During the optional Extension and Prolongation of Extension periods, dose levels and intervals alter depending on PASI score.

Proportion of subjects with a ≥90% improvement in Psoriasis Area and Severity Index (PASI90) at week 12

The PASI combines the extent of body surface involvement in the body regions head, trunk, arms, and legs. The percent area of the skin involved is estimated per region (0-100%). The severity is estimated by clinical signs of erythema, induration and scaling, from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Overall scores range from 0 (no psoriasis) to 72 (the most severe disease). PASI90 is a ≥90% reduction from Baseline in PASI score

The sPGA is the physician's determination of the subject's Psoriasis lesions overall at a given time point, with the grading 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe)

The NAPSI scale is used to evaluate the severity of psoriasis in the fingernail bed and matrix. The nail is divided into quadrants. Each quadrant is given the score 0 (absence) or 1 (presence) for psoriasis in the beds and matrix, respectively. The NAPSI score of a nail is the sum of each quadrant. The maximum score per nail is 8. In the target nail NAPSI, the worst affected nail at Baseline is evaluated throughout the study.

DLQI is a 10-question quality-of-life questionnaire completed by the subject. It covers 6 the domains symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The total scores range from 0 to 30, with higher score indicating greater quality of life impairment.

Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Prolongation of Extension period

Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Prolongation of Extension period

Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Prolongation of Extension period

Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Prolongation of Extension period

Proportion of subjects achieving an absolute PASI score ≤1 at end of Prolongation of Extension period

Proportion of subjects achieving an absolute PASI score <3 at end of Prolongation of Extension period

Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Extension period

Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Prolongation of Extension period

Inclusion Criteria: Diagnosed with plaque psoriasis of at least 6 months prior to Screening, without clinically significant flares during the 12 weeks before randomization, with or without psoriatic arthritis Having precedent failure, intolerance and/or contraindication to at least two standard therapies for moderate to-severe plaque psoriasis (systemic therapy and/or phototherapy), and previousinsufficient disease control of topical therapy (e.g. corticosteroids, vitamin D derivatives, cignolin/dithranol). Moderate-to-severe plaque psoriasis at Screening and at Baseline as defined by: i. Psoriasis involving ≥10% BSA ii. PASI score of ≥ 12 iii. sPGA score of ≥ 3 Use of highly effective method of contraception or female of non-childbearing potential Exclusion Criteria: Current forms of psoriasis other than chronic plaque-type Current drug induced psoriasis History of hypersensitivity or allergy to the IMP or its excipients History of recurrent or medically important infections requiring intervention and/or systemic treatment in the last 12 months, including infections with e.g. candida and Staphylococcus aureus History of or any signs of lymphoproliferative disease, or a known malignancy or a history of malignancy within the previous 5 years (with the exception of basal cell or squamous cell carcinoma of the skin that had been fully excised with no evidence of recurrence) Autoimmune disease of relevance Inflammatory Bowel Disease requiring treatment within the past 12 months Clinically significant heart condition which is not well controlled by current therapy, as assessed by the Investigator Significantly immunocompromised subject Blood pressure out of range Laboratory values out of range, including ALT, AST, eGFR Positive to HIV, hepatitis B, hepatitis C or tuberculosis Recent previous psoriasis treatments, within defined wash-out periods Prior exposure to systemic psoriasis treatments with anti-IL-17 biological therapies Live vaccination within defined time restrictions Inability or unwillingness to limit ultraviolet (UV) light exposure during the course of the study Pregnancy, breast feeding Drug and/or alcohol abuse or dependence

RuhrDerm - Studienzentrum der Gemeinschaftspraxis für Dermatologie, Venerologie, Allergologie, Phlebologie