A Study to Evaluate ABY-035 in Subjects With Moderate-to-severe Plaque Psoriasis

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Biological: ABY-035
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABY-035 2 mg<br>2 mg ABY-035 SC | Biological: ABY-035<br>* ABY-035 solution for injection<br>|
| Experimental: ABY-035 20 mg<br>20 mg ABY-035 SC | Biological: ABY-035<br>* ABY-035 solution for injection<br>|
| Experimental: ABY-035 80 mg<br>80 mg ABY-035 SC | Biological: ABY-035<br>* ABY-035 solution for injection<br>|
| Experimental: ABY-035 160 mg<br>160 mg ABY-035 SC | Biological: ABY-035<br>* ABY-035 solution for injection<br>|
| Placebo Comparator: Placebo<br>Placebo, switching to 80 mg ABY-035 after 12 weeks | Biological: Placebo<br>* Placebo to ABY-035 solution for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in target nail Nail Psoriasis Severity Index (NAPSI) at week 12 | 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. | Week 12 | 
| Change from baseline in target nail NAPSI at week 24 | NAPSI: Nail Psoriasis Severity Index | Week 24 | 
| Change from baseline in target nail NAPSI at week 52 | NAPSI: Nail Psoriasis Severity Index | Week 52 | 
| Proportion of subjects achieving Dermatology Life Quality Index (DLQI) of 0 or 1 at week 12 | 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. | Week 12 | 
| Proportion of subjects achieving DLQI of 0 or 1 at week 24 | DLQI: Dermatology Life Quality Index | Week 24 | 
| Proportion of subjects achieving DLQI of 0 or 1 at week 52 | DLQI: Dermatology Life Quality Index | Week 52 | 
| Proportion of subjects achieving DLQI of ≤ 5 at Week 12 | DLQI: Dermatology Life Quality Index | Week 12 | 
| Proportion of subjects achieving DLQI of ≤ 5 at Week 24 | DLQI: Dermatology Life Quality Index | Week 24 | 
| Proportion of subjects achieving DLQI of ≤ 5 at Week 52 | DLQI: Dermatology Life Quality Index | Week 52 | 
| Change from baseline in DLQI at week 12 | DLQI: Dermatology Life Quality Index | Week 12 | 
| DLQI at week 24 compared to baseline | DLQI: Dermatology Life Quality Index | Week 24 | 
| DLQI at week 52 compared to baseline | DLQI: Dermatology Life Quality Index | Week 52 | 
| Change from baseline in pain-Visual Analogue Scale (VAS) at week 12 | Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain) | Week 12 | 
| Pain-VAS score at Week 24 compared to baseline | Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain) | Week 24 | 
| Pain-VAS score at Week 52 compared to baseline | Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain) | Week 52 | 
| Change from baseline in itch-Visual Analogue Scale (VAS) at week 12 | Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch) | Week 12 | 
| Itch-VAS at week 24 compared to baseline | Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch) | Week 24 | 
| Itch-VAS at week 52 compared to baseline | Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch) | Week 52 | 
| Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 | AUC is a measure of the drug exposure | 52 weeks | 
| Levels of anti-ABY-035 antibodies in serum | Anti-drug antibodies | 52 weeks | 
| Number of treatment emerging Adverse Events during the Extension period | Adverse Events starting after first administration of study drug | Week 52 to Week 104 | 
| Number of treatment emerging Adverse Events during the Prolongation of Extension period | Adverse Events starting after first administration of study drug | Week 104 to Week 156 | 
| Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 during the Extension period | AUC is a measure of the drug exposure | Week 52 to Week 104 | 
| Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 during the Prolongation of Extension period | AUC is a measure of the drug exposure | Week 104 to Week 156 | 
| Levels of anti-ABY-035 antibodies in serum during the Extension period | Anti-drug antibodies | Week 52 to Week 104 | 
| Levels of anti-ABY-035 antibodies in serum during the Prolongation of Extension period | Anti-drug antibodies | Week 104 to Week 156 | 
| Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Extension period | A ≥90% reduction from Baseline in PASI score | Week 104 | 
| Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Prolongation of Extension period | A ≥90% reduction from Baseline in PASI score | Week 156 | 
| Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Extension period | A ≥50% reduction from Baseline in PASI score | Week 104 | 
| Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Prolongation of Extension period | A ≥50% reduction from Baseline in PASI score | Week 156 | 
| Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Extension period | A ≥75% reduction from Baseline in PASI score | Week 104 | 
| Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Prolongation of Extension period | A ≥75% reduction from Baseline in PASI score | Week 156 | 
| Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Extension period | A 100% reduction from Baseline in PASI score | Week 104 | 
| Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Prolongation of Extension period | A 100% reduction from Baseline in PASI score | Week 156 | 
| Change from baseline in PASI score at end of Extension period | PASI: Psoriasis Area and Severity Index | Week 104 | 
| Change from baseline in PASI score at end of Prolongation of Extension period | PASI: Psoriasis Area and Severity Index | Week 156 | 
| Proportion of subjects achieving an absolute PASI score ≤1 at end of Extension period | PASI ≤1 equals clear or almost clear skin | Week 104 | 
| Proportion of subjects achieving an absolute PASI score ≤1 at end of Prolongation of Extension period | PASI ≤1 equals clear or almost clear skin | Week 156 | 
| Proportion of subjects achieving an absolute PASI score <3 at end of Extension period | PASI: Psoriasis Area and Severity Index | Week 104 | 
| Proportion of subjects achieving an absolute PASI score <3 at end of Prolongation of Extension period | PASI: Psoriasis Area and Severity Index | Week 156 | 
| Proportion of subjects achieving sPGA of 0 or 1 at end of Extension period | sPGA: Static Physician's Global Assessment | Week 104 | 
| Proportion of subjects achieving sPGA of 0 or 1 at end of Prolongation of Extension period | sPGA: Static Physician's Global Assessment | Week 156 | 
| Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Extension period | sPGA: Static Physician's Global Assessment | Week 104 | 
| Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Prolongation of Extension period | sPGA: Static Physician's Global Assessment | Week 156 | 
| Change from baseline in sPGA at end of Extension period | sPGA: Static Physician's Global Assessment | Week 104 | 
| Change from baseline in sPGA at end of Prolongation Extension period | sPGA: Static Physician's Global Assessment | Week 156 | 
| Change from baseline in target nail NAPSI at end of Extension period | NAPSI: Nail Psoriasis Severity Index | Week 104 | 
| Change from baseline in target nail NAPSI at end of Prolongation of Extension period | NAPSI: Nail Psoriasis Severity Index | Week 156 | 
| Proportion of subjects achieving DLQI of 0 or 1 at end of Extension period | DLQI: Dermatology Life Quality Index | Week 104 | 
| Proportion of subjects achieving DLQI of 0 or 1 at end of Prolongation of Extension period | DLQI: Dermatology Life Quality Index | Week 156 | 
| Proportion of subjects achieving DLQI of ≤ 5 at end of Extension period | DLQI: Dermatology Life Quality Index | Week 104 | 
| Proportion of subjects achieving DLQI of ≤ 5 at end of Prolongation of Extension period | DLQI: Dermatology Life Quality Index | Week 156 | 
| DLQI at end of Extension period compared to baseline | DLQI: Dermatology Life Quality Index | Week 104 | 
| DLQI at end of Prolongation of Extension period compared to baseline | DLQI: Dermatology Life Quality Index | Week 156 | 
| Pain-VAS score at end of Extension period compared to baseline | Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain) | Week 104 | 
| Pain-VAS at end of Prolongation of Extension period compared to baseline | Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain) | Week 156 | 
| Itch-VAS at end of Extension period compared to baseline | Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch) | Week 104 | 
| Itch-VAS at end of Prolongation of Extension period compared to baseline | Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch) | Week 156 | 
| Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 12 | A ≥50% reduction from Baseline in PASI score | 12 weeks | 
| Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 24 | A ≥50% reduction from Baseline in PASI score | 24 weeks | 
| Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 52 | A ≥50% reduction from Baseline in PASI score | 52 weeks | 
| Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 12 | A ≥75% reduction from Baseline in PASI score | 12 weeks | 
| Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 24 | A ≥75% reduction from Baseline in PASI score | 24 weeks | 
| Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 52 | A ≥75% reduction from Baseline in PASI score | 52 weeks | 
| Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 12 | A 100% reduction from Baseline in PASI score | 12 weeks | 
| Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 24 | A 100% reduction from Baseline in PASI score | 24 weeks | 
| Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 52 | A 100% reduction from Baseline in PASI score | 52 weeks | 
| Change from baseline in PASI score at week 12 | PASI: Psoriasis Area and Severity Index | Week 12 | 
| Change from baseline in PASI score at week 24 | PASI: Psoriasis Area and Severity Index | Week 24 | 
| Change from baseline in PASI score at week 52 | PASI: Psoriasis Area and Severity Index | Week 52 | 
| Proportion of subjects achieving an absolute PASI score ≤1 at week 12 | PASI ≤1 equals clear or almost clear skin | 12 weeks | 
| Proportion of subjects achieving an absolute PASI score ≤1 at week 24 | PASI ≤1 equals clear or almost clear skin | 24 weeks | 
| Proportion of subjects achieving an absolute PASI score ≤1 at week 52 | PASI ≤1 equals clear or almost clear skin | 52 weeks | 
| Proportion of subjects achieving an absolute PASI score <3 at week 12 | PASI: Psoriasis Area and Severity Index | 12 weeks | 
| Proportion of subjects achieving an absolute PASI score <3 at week 24 | PASI: Psoriasis Area and Severity Index | 24 weeks | 
| Proportion of subjects achieving an absolute PASI score <3 at week 52 | PASI: Psoriasis Area and Severity Index | 52 weeks | 
| Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 12 | 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) | 12 weeks | 
| Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 24 | sPGA: Static Physician's Global Assessment | 24 weeks | 
| Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 52 | sPGA: Static Physician's Global Assessment | 52 weeks | 
| Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 12 | sPGA: Static Physician's Global Assessment | 12 weeks | 
| Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 24 | sPGA: Static Physician's Global Assessment | 24 weeks | 
| Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 52 | sPGA: Static Physician's Global Assessment | 52 weeks | 
| Change from baseline in sPGA at week 12 | sPGA: Static Physician's Global Assessment | 12 weeks | 
| Change from baseline in sPGA at week 24 | sPGA: Static Physician's Global Assessment | 24 weeks | 
| Change from baseline in sPGA at week 52 | sPGA: Static Physician's Global Assessment | 52 weeks | 
| Number of treatment emergent Adverse Events | Adverse Events starting after first administration of study drug | 52 weeks | 
| Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 24 | A ≥90% reduction from Baseline in PASI score | 24 weeks | 
| Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 52 | A ≥90% reduction from Baseline in PASI score | 52 weeks |