Proof-of-concept Study of Forward Pharma (FP)187 in Patients With Mild/Moderate Psoriatic Arthritis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate, whether FP187 is effective in the treatment of mild to moderate psoriatic arthritis.

Detailed Description
-----------------
The study is randomised, double blind, placebo-controlled proof-of-concept trial to investigate the efficacy and safety of FP187 compared to placebo over 24 weeks of treatment in patients with mild to moderate psoriatic arthritis (PsA). The daily dose levels in the FP187 arm will be 500 mg. After completion of the double blind treatment of 24 weeks, all patients irrespective of their treatment arm will be switched to an additional 24 week open-label treatment phase with 500 mg / day FP187. Patient who do not complete the 24 week double blind part of the study as scheduled will not be eligible for participation in the open-label part.

Official Title
-----------------
A Randomized, Double Blind, Placebo-controlled Proof-of-concept Study of FP187 in Patients With Mild to Moderate Psoriatic Arthritis

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

Intervention / Treatment
-----------------
* Drug: FP187
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: documented clinical diagnosis of mild to moderate psoriatic arthritis of at least 3 months active psoriatic arthritis with at least 2 tender and 2 swollen joints signed informed consent willingness and ability to comply with study procedures besides psoriatic arthritis, patient must be in good general health in the opinion of the investigator, as determined by medical history, physical examination, vital signs, electrocardiography and clinical laboratory parameters if patients are using methotrexate, they should be on a stable dosis of not more the 20mg per week for at least 90 days prior to study entrance and should present no serious toxic side effects attributable to methotrexate female of childbearing age must be either surgically sterile or use a highly effective medically accepted contraceptive method Exclusion Criteria: female patients who are pregnant of breast-feeding or planning to become pregnant during the entire trial period male patients planning pregnancy with their partner during the entire trial period, or practicing unprotected sexual relationship during the entire trial period known allergy to any of the constituents of the products being tested known immunosuppressive diseases (e.g. HIV, AIDS) known history of latent or active granulomatous infection including tuberculosis, histoplasmosis or coccidioidomycosis presence of another inflammatory disease including but not limited to rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematous or Lyme disease presence of chronic widespread pain syndrome patients with pustular forms of psoriasis, erythrodermic or guttate psoriasis patients with another non-psoriatic arthropathy (e.g. osteoarthritis) presence of another serious or progressive disease including skin malignancy presence or history of any malignancy (except for basal cell carcinoma, squamous cell carcinoma in situ of the skin treated with no evidence of recurrence within 5 years, or cervix cancer in situ treated with no evidence of recurrence.) use at any time of an biological Disease Modifying Antirheumatic Drug (bDMARD) such as etanercept, adalimumab, golimumab, certolizumab pegol or infliximab corticosteroid injections within 12 weeks use of any dimethyl fumarate (DMF) containing product within 12 weeks use of any retinoid treatments, other immunosuppressive treatments, cytostatics or drugs with known harmful effects on the kidneys within the last 3 months use of cyclosporine, corticosteroids or psoralen + UVA (PUVA) treatment within 4 weeks ongoing stomach or intestinal problems (e.g. gastritis or peptic ulcer) Aspartate transaminase (AST) or Alanine transaminase (ALT) > 2x upper normal normal limit (UNL) or Gamma Glutamyl Transferase (gamma-GT) results >2.5 UNL estimated creatinine clearance (Cockcroft-Gault) < 60ml/min leucopenia (leucocyte count < 3.5/nl), eosinophilia (>750 / micro l) or lymphocytopenia (<1.02 / nl) protein detected by urine stick test participation in another clinical trial during the last 2 months or participation in a trial with another psoriatic arthritis treatment within 6 months

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental FP187<br>Treatment with a daily dose of 500mg FP187 (twice daily). Other names: Dimethyl fumarate | Drug: FP187<br>* FP 187 is given as oral tablets twice daily, 500 mg daily<br>* Other names: Dimethyl Fumarate;|
| Placebo Comparator: Placebo Comparator<br>Patients will receive the same number of tablets as patients randomized to FP187 arm in order to maintain the blind. The colour and shape of the FP187 and placebo tablets will be the same so that no visible difference is detectable | Drug: Placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American Congress of Rheumatology (ACR)20 | Proportion of patients with a 20% improvement from baseline in tender/swollen joint counts according to the American College of Rheumatology criteria (ACR) based on a 66/68 joint count. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR 20 | Proportion of patients with a 20% improvement from baseline in tender/swollen joint counts according to the American College of Rheumatology criteria (ACR) based on a 66/68 joint count. | Weeks 8, 12, 28, 36, 40, 52 | 
| BSA | Body Surface Area (BSA) affected by psoriasis | Weeks 8, 12, 24, 28, 36, 40, 52 | 
| LEI | Change from baseline in the Leeds Enthesitis Index (LEI) | Weeks 8, 12, 24, 28, 36, 40, 52 | 
| ACR 50 | Proportion of patients with a 50% improvement from baseline in tender/swollen joint counts according to the American College of Rheumatology criteria (ACR) based on a 66/68 joint count. | Weeks 8, 12, 24, 28, 36, 40, 52 | 
| ACR 70 | Proportion of patients with a 70% improvement from baseline in tender/swollen joint counts according to the American College of Rheumatology criteria (ACR) based on a 66/68 joint count. | Weeks 8, 12, 24, 28, 36, 40, 52 | 
| Pain | Change from baseline in Pain Visual Analogue Scale (VAS) score | Weeks 8, 12, 24, 28, 36, 40, 52 | 
| EQ-5D | Change from baseline in European Quality of Life - 5 Dimensions (EQ-5D) score | Weeks 8, 12, 24, 28, 36, 40, 52 | 
| BASDAI | Change from baseline in Bath Ankylosing Spondylitis Disease Activity (BASDAI) score | Weeks 8, 12, 24, 28, 36, 40, 52 | 
| BASFI | Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score | Weeks 8, 12, 24, 28, 36, 40, 52 | 
| HAQ | Change from baseline in Health Assessment Questionnaire (HAQ) score | Weeks 8, 12, 24, 28, 36, 40, 52 |