A Study to Investigate Efficacy, Tolerability and Safety of ABY-035 in Patients With Active Psoriatic Arthritis

Study Overview
=================
Brief Summary
-----------------
This is a Phase II, prospective, multicenter, randomized, double-blind, placebo-controlled, dose finding trial in parallel-groups with primary endpoint at Week 16 (visit V9) to investigate the efficacy, tolerability, safety, pharmacokinetics and immunogenicity of ABY-035 in adult patients with PsA.

Detailed Description
-----------------
The study evaluates two dose levels of ABY-035, in comparison to placebo, in subjects with psoriatic arthritis. The clinical trial duration is 72 weeks (Screening - last FU visit) comprised of up to 4 weeks of screening, 44 weeks of double-blind-treatment, and 24 weeks of follow-up. Treatment Periods are: Treatment Period I: from V1 (Week 0) to V9 (Week 16) Treatment Period II: from V9 (Week 16) to V16 (Week 44: last dosing) At visit V1 (Week 0), patients who meet the entry criteria will be randomly assigned in equal rates (1:1:1) to one of three parallel groups (A, B, C). The treatment will be administered once every 2 weeks (Q2W). Patients assigned to groups A and B will receive active treatment from V1 to V16 (group A = 40 mg ABY-035; group B = 80 mg ABY-035). Patients initially assigned to placebo will switch to active treatment at visit V9 in a blinded fashion (group C = Placebo from V1 to V8 and 80 mg ABY-035 from V9 to V16).

Official Title
-----------------
A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-finding Clinical Trial in Patients With Active Psoriatic Arthritis to Investigate Efficacy, Tolerability, Safety, Pharmacokinetics and Immunogenicity of ABY-035

Conditions
-----------------
Psoriatic Arthritis

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Patient who has given his / her signed declaration of consent and data protection declaration At least 18 years and less than 75 years of age at Screening visit Psoriatic arthritis with inflammatory musculoskeletal disease (joint, spine, or entheseal) with the presence of ≥3 points from the five categories of the Classification Criteria for Psoriatic Arthritis (CASPAR) at any timepoint in medical history. Active psoriatic arthritis defined by: ≥3 swollen joints out of 66 joints (SJC66) at Screening visit and Baseline visit ≥3 tender joints out of 68 (TJC68) at Screening visit and Baseline visit Precedent failure or insufficient treatment response to or contraindication or intolerability to nonsteroidal anti-inflammatory drug (NSAID), csDMARD (i.e. MTX, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine A), and/or TNFi (e.g. adalimumab, infliximab, etanercept, golimumab, certolizumab) Rheumatoid factor (RF) and anti-CCP antibody negative Presence or history of plaque psoriasis Exclusion Criteria: Underlying conditions which significantly immunocompromise the patient and / or place the patient at unacceptable risk for receiving an immunomodulatory therapy History of or current relevant autoimmune diseases (e.g. rheumatoid arthritis, primary ankylosing spondylitis, systemic lupus erythematosus) other than psoriasis or psoriatic arthritis History of or current fibromyalgia or pain syndrome Uncontrolled inflammatory bowel disease Presence or history of recurrent or medically important infections in the last 6 months prior to Baseline visit Clinically relevant Candida infection requiring systemic treatment within the last 6 months prior to Baseline visit History or any signs of lymphoproliferative disease, or a known malignancy or a history of malignancy within the previous 5 years Insufficiently controlled heart failure Current uncontrolled arterial hyper- or hypotension

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABY-035 40 mg<br>40 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>|
| Placebo Comparator: Placebo<br>Placebo, switching to 80 mg ABY-035 after 16 weeks | Biological: Placebo<br>* Placebo to ABY-035 solution for injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology 50 response rate (ACR50) | ACR50 response rate at V9 (Week 16) for higher Dose vs. Placebo | 16 weeks | 
| ACR50 | ACR50 response rate at V7 (Week 12) for higher Dose vs. Placebo | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20/70 | ACR20/70 response rate, percentage of patients achieving Minimal Disease Activity (MDA): at V9 (Week 16) for higher Dose vs. Placebo | 16 weeks | 
| ACR20/70 | ACR20/70 response rate, percentage of patients achieving MDA: at V7 (Week 12) for higher Dose vs. Placebo | 12 weeks | 
| ACR20/50/70 | ACR20/50/70 response rate, percentage of patients achieving MDA: at V9 (Week 16) for Lower Dose vs. Placebo | 16 weeks | 
| ACR20/50/70 | ACR20/50/70 response rate, percentage of patients achieving MDA: at V7 (Week 12) for Lower Dose vs. Placebo | 12 weeks | 
| ACR 20/50/70 | ACR 20/50/70 response rate, percentage of patients achieving MDA: at V5 (Week 8) for higher Dose vs. Placebo | 8 weeks |