Rheumatoid Arthritis MedDRA version: 23.1 Level: LLT Classification code 10003268 Term: Arthritis rheumatoid System Organ Class: 100000004859
Conditions
Interventions
Product Name: AP1189 Tablet
Pharmaceutical Form: Tablet
INN or Proposed INN: NA
CAS Number: 1809420-72-1
Current Sponsor code: AP1189
Other descriptive name: 2-[(E)-[(E)-3-[1-(2-nitrophenyl)pyrrol-2-y
Sponsors
SynAct Pharma ApS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria are the same for the Part A and the Part B population: 1. Written informed consent has been obtained prior to initiating any study specific procedures 2. Male and female subjects, 18 to 85 years of age 3. Confirmed diagnosis of RA according to the 2010 ACR/EULAR RA classification criteria and ACR class I-III a. = 6 swollen joints (based on 66 joint counts) and = 6 tender joints (based on 68 joint counts) b. Must meet at least one of the following parameters at Screening: i. A positive result for anti-CCP or RF, OR ii. Serum CRP = 6 mg/L based on central laboratory value 4. Ongoing methotrexate therapy =12 weeks in a stable dose of 7.5 to 25 mg/week for at least 4 weeks prior to the baseline visit 5. Subject has an inadequate clinical response to maximally tolerated methotrexate therapy 6. Subjects should be receiving an adequate and prescribed stable dose of folic acid (=5 mg/week total dose or as per local clinical practice) which should be confirmed or initiated at screening and continued throughout the study 7. Negative QuantiFERON-in-Tube test (QFG-IT) (Mantoux test can be used if QFGIT is not possible) 8. Subjects should be able to complete (read and write) the Patient-Reported Outcome questionnaires (PRO questionnaires) 9. Females of childbearing potential must have a negative pregnancy test at screening and again at baseline 10. Sexually active females of childbearing potential and male participants are excluded if not practicing two different methods of birth control with their partner during the study and for at least 90 days after the last dose of study drug or who will not remain abstinent during the study and for 90 days after the last dose. If employing birth control, each couple must use two of the following precautions: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control implant, birth control depot injections, condom with spermicide, or sponge with spermicide. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 140
Exclusion criteria
Exclusion criteria: Exclusion criteria are the same for the Part A and the Part B populations: 1. Use of all other biologic or nonbiologic DMARDs and immunosuppressive therapy within 4 weeks or five half-lives (whichever is longer) prior to administration of the first dose of study drug 2. Oral steroids at a dose >10 mg/day of prednisone (or equivalent) or a prescription for oral steroids which has changed within 4 weeks of baseline 3. Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to baseline 4. Participation in any other study involving investigational drug(s) within 4 weeks prior to baseline 5. Major surgery (including joint operation) within 8 weeks prior to screening or planned surgery within the period of the study participation 6. Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty’s syndrome). Sjögren’s syndrome with RA is allowable 7. Functional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedbound 8. Prior history of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) 9. Subjects with fibromyalgia 10. Initiation or change in dose for NSAIDs (including low-dose aspirin and COX-2 inhibitors) within 2 weeks prior to baseline 11. Evidence of serious uncontrolled concomitant cardiovascular (including clinically significantly prolonged QTc interval), nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease 12. Serum Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than 1.5 x the upper limit of normal (ULN) and alkaline phosphatase (ALP) and/or bilirubin values above the ULN at the screening visit. 13. Prior renal transplant, current renal dialysis, or moderate to severe renal insufficiency (determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault formula of =60 ml/min/1,73m²) 14. Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids 15. Evidence of active malignant disease (except basal cell carcinoma of the skin that has been excised and cured) 16. Pregnant women or nursing (breastfeeding) mothers 17. History of alcohol, drug, or chemical abuse within the 6 months prior to screening 18. Neuropathy or other painful, chronic conditions that might interfere with pain evaluation 19. Body weight of >150 kg 20. HBsAg positive and/or Anti-HBc with sign of current infection. Participants with positive Anti-HBc should be tested for IgM anti-HBc - if IgM anti-HBc is positive the patient will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary safety Objective Part A: The primary safety objective is to evaluate the safety and tolerability of 4 weeks treatment with multiple doses AP1189 once daily to determine the suitable doses to be tested in Part B. Part B: The primary safety objective is to evaluate the safety and tolerability of 12 weeks treatment with multiple doses of AP1189 once daily. Primary efficacy Objective Part A: The primary efficacy objective is to evaluate the efficacy of 4 weeks treatment with multiple doses AP1189 once daily to help define the suitable doses to be tested in Part B. Part B: The primary efficacy objective is to evaluate the efficacy of 12 weeks treatment with multiple doses AP1189 once daily. ;Secondary Objective: Secondary efficacy Objectives The secondary efficacy objectives are to evaluate the efficacy of AP1189 on various responder criteria, composite endpoints, quality of life, fatigue and use of rescue medication.;Primary end point(s): Primary Safety Endpoint • Adverse events (AE), physical examinations, vital sign measurements, electrocardiogram (ECG), and clinical laboratory testing (hematology, chemistry, and urinalysis) Primary Efficacy Endpoint • Effect of AP1189 compared to placebo in subjects with RA, evaluated by American College of Rheumatology 20% (ACR20) response rate at Week 4 (Part A) and Week 12 (Part B) ;Timepoint(s) of evaluation of this end point: Week 4 (Part A) and week 12 (Part B) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints The secondary efficacy endpoints are to compare the effects of multiple doses AP1189 against placebo by assessing: Response rates evaluated by the American College of Rheumatology 50% (ACR50) at Week 4 (Part A) and Week 12 (Part B) • Response rates evaluated by the American College of Rheumatology 70% (ACR70) at Week 4 (Part A) and Week 12 (Part B)Time from Baseline to when subjects achieve American College of Rheumatology response criteria (ACR20, 50 and 70) • Changes in clinical disease activity evaluated by a reduction in the Clinical Disease Activity Index (CDAI) from Baseline to Week 4 (Part A) or Week 12 (Part B). • Changes in clinical disease activity evaluated by reduction in DAS-28 (CRP) from Baseline to Week 4 (Part A) or Week 12 (Part B). • Proportion of subjects achieving Moderate Disease Activity based on CDAI at Weeks 2 and 4 (Part A) or Weeks 2, 4, 8 and 12 (Part B) • Proportion of subjects achieving Low Disease Activity based on CDAI at Weeks 2 and 4 (Part A) or Weeks 2, 4, 8 and 12 (Part B) • Proportion of subjects achieving disease remission based on CDAI at Weeks 2 and 4 (Part A) or Weeks 2, 4, 8 and 12 (Part B) • Proportion of subjects achieving Moderate Disease Activity based on DAS28(CRP) = 5.1 at Weeks 2 and 4 (Part A) or Weeks 2, 4, 8 and 12 (Part B) • Proportion of subjects achieving Low Disease Activity based on DAS28(CRP) = 3.2 at Weeks 2 and 4 (Part A) or Weeks 2, 4, 8 and 12 (Part B) • Proportion of subjects achieving disease remission based on DAS28(CRP) < 2.6 at Weeks 2 and 4 (Part A) or Weeks 2, 4, 8 and 12 (Part B) • Proportion of subjects treated with corticosteroids as rescue medication • Number of intra-articular corticosteroid injections given as rescue medication • Time from Baseline to rescue medication use • Change in subject-reported quality of life (using Health Assessment Questionnaire – Disability Index (HAQ-DI)) from Baseline to Week 4 (Part A) or Week 12 (Part B) • Cha | — |
Countries
Bulgaria, Moldova, Republic of, United States
Contacts
Public ContactRegulatory Affairs
NBCD A/S
Outcome results
None listed