A Study of the Safety, Tolerability and Efficacy of Treatment With AP1189 in Early RA Patients With Active Joint Disease

Phase 2

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: 50 mg AP1189
Drug: Placebo
Drug: AP1189

Registration Number: NCT04004429

Lead Sponsor: SynAct Pharma Aps

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 105

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
Females of child-bearing potential may only participate if using reliable means of contraception or are post-menopausal. Surgically sterilized women at least 6 months prior to screening
Females of childbearing potential must have a negative pregnancy test at screening and baseline

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)
Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
Evidence of active malignant disease
Pregnant women or nursing mothers
History of alcohol, drug, or chemical abuse within the 6 months prior to screening
Neuropathies or other painful conditions that might interfere with pain evaluation
Body weight of >150 kg

Exclusion criteria that only applies for Norway

Evidence of moderate and/or severe organ dysfunction
Abnormal chest x-ray (as per the discretion of the investigator
Evidence of positive hepatitis serology
Evidence of peptic ulcer disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
50 mg AP1189	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.
Placebo	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.
100 mg AP1189	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.

Primary Outcome Measures

Name	Time	Method
Change in Clinical Disease Activity Index (CDAI)	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 Outcome Measures

Name	Time	Method
ACR (American College of Rheumatology) Response	4 weeks	Proportion of subjects achieving a response assessed by ACR70. The ACR response rate ACR70 is defined as ≥70% improvement in swollen and tender joint counts (SJC/TJC) and 3 of the following 5 assessments: Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, Patient's Assessment of Pain, Health Assessment Questionnaire - Disability Index or C-Reactive Protein. Proportion in the context of this protocol refers to number of participants.