A Double-blind, Multicenter, Two-part, Randomized, Placebo-controlled Study of the Safety, Tolerability, and Efficacy of 4 Weeks Treatment With AP1189 in Early Rheumatoid Arthritis (RA) Patients With Active Joint Disease
Overview
- Phase
- Phase 2
- Intervention
- 50 mg AP1189
- Conditions
- Rheumatoid Arthritis
- Sponsor
- SynAct Pharma Aps
- Enrollment
- 105
- Locations
- 2
- Primary Endpoint
- Change in Clinical Disease Activity Index (CDAI)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) > 22, who are to start up-titration with methotrexate.
Detailed Description
A multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) \> 22, who are to start up-titration with methotrexate. The study will be conducted in two parts separated by an interim analysis. Part 1: The subjects will be randomized in a 1:1:1 ratio into: . * AP1189 dose 50 mg * AP1189 dose 100 mg * placebo INTERIM ANALYSIS Part 2: All subjects will be randomized into either design 1, 2 or 3 based on data from the interim analysis. * Design 1: AP1189 dose 50 mg or placebo in a 2:1 ratio * Design 2: AP1189 dose 100 mg or placebo in a 2:1 ratio * Design 3: Continue with the same doses as in Part 1 The purpose of this study is to determine the safety and efficacy of 2 doses of AP1189 compared with placebo after 4 weeks of treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent has been obtained prior to initiating any study specific procedures
- •Male and female subjects, 18 to 85 years of age
- •Confirmed diagnosis of RA (Rheumatoid Arthritis) according to the 2010 American College of Rheumatology (ACR)/EULAR RA classification criteria
- •Polyarthritis with joint swelling and tenderness of a minimum of three joints out of 68 joints tested
- •Candidate for Methotrexate treatment
- •Is about to begin treatment with MTX (Methotrexate)
- •Tested positive for anti-CCP (Anti-cyclic citrullinated peptide) or RF (Rheumatoid Factor)
- •Severe active RA (Clinical Disease Activity Index (CDAI)) \> 22) at screening and baseline
- •Negative QFG-IT (QuantiFERON-in-Tube test)
- •Subjects should be able to complete the PRO (Patient Reported Outcome) questionnaires
Exclusion Criteria
- •Participation in any other study involving investigational drug(s) within 4 weeks prior to study entry
- •Major surgery within 8 weeks prior to screening or planned surgery within 1 month following randomization
- •Rheumatic autoimmune disease other than RA, including SLE (systemic Lupus Erythematosus), MCTD (Mixed Connective Tissue Disease), scleroderma, polymyositis, or significant systemic involvement secondary to RA. Sjögren syndrome with RA is allowable
- •Functional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedbound
- •Prior history of or current inflammatory joint disease other than RA
- •Subjects with fibromyalgia
- •Initiation or change in dose for NSAIDs within 2 weeks prior to dosing with the IMP (Investigational Medicinal Product)
- •Corticosteroids are prohibited within 2 weeks prior to screening (and during the entire treatment period and until the final visit
- •Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease
- •Have prior renal transplant, current renal dialysis or severe renal insufficiency (determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault Formula of ≤30 mL/min/1,73 m2 calculated by the local lab)
Arms & Interventions
50 mg AP1189
50 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water.
Intervention: 50 mg AP1189
100 mg AP1189
100 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water.
Intervention: AP1189
Placebo
Placebo. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension i e. the powder will be added 50 ml water.
Intervention: Placebo
Outcomes
Primary Outcomes
Change in Clinical Disease Activity Index (CDAI)
Time Frame: 4 weeks
The change in CDAI after 4 weeks treatment compared to baseline. CDAI is calculated as a sum of: * SJC (28): Number of Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees); * TJC (28): Number of Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) * PGA: Patient Global Disease Activity (patient's self-assessment of overall RA disease activity on a scale 0-100, where 100 is maximal activity) * IGA: Physician's Global Disease Activity (evaluator's assessment of the subject's overall RA disease activity on a scale 0-100, where 100 is maximal activity). The CDAI score range is from 0 - 76, whereas a score of: ≤2.8 means Remission \>2.8 and ≤10 means Low Disease Activity \>10 and ≤22 means Moderate Disease Activity \>22 means High Disease Activity For the purpose of this study, a decrease in CDAI (improvement) is reported as - xx.xx).
Secondary Outcomes
- ACR (American College of Rheumatology) Response(4 weeks)