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: Not applicable
CAS Number: 1809420-72-1
Current Sponsor code: AP1189
Other descriptive name: N''-[(E)-[(2E)-3-[1-(2-nitrop
Sponsors
SynAct Pharma ApS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 are ACR class I-III (See Section 22.1) 4. = 6 swollen joints (based on 66 joint counts) and = 6 tender joints (based on 68 joint counts). For participants participating in the MRI sub-study, at least one affected joint must be in the hand/wrist. 5. Candidate for MTX treatment 6. Is about to begin treatment with MTX 7. Must meet at least one of the following parameters at Screening: a) A positive result for anti-Cyclic Citrullinated Peptide (anti-CCP) or rheumatoid factor (RF) OR b) Serum CRP = 6 mg/L 8. Highly active RA (CDAI > 22) at screening and baseline 9. Negative QuantiFERON-in-Tube test (QFG-IT) (Mantoux test can be used if QFG-IT is not possible) 10. Subjects should be able to complete (read and write) the Patient-Reported Outcome questionnaires (PRO questionnaires) 11. Females of child-bearing potential may only participate if using a highly effective method of contraception (for detailed information see section22.3) or are post-menopausal (menstrual periods stopped at least 12 months ahead of the enrolment in the trial) Surgically sterilized women at least 6 months prior to screening 12. Females of childbearing potential must have a negative pregnancy test at screening and baseline. 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 92 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Participation in any other study involving investigational drug(s) within 4 weeks prior to study entry 2. Major surgery (including joint operation) within 8 weeks prior to screening or planned surgery within 1 month following randomization 3. 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 4. Functional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedbound 5. Prior history of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) 6. Subjects with fibromyalgia 7. Use of hydroxychloroquine within 4 weeks prior the Screening Visit 8. Initiation of, or change in existing NSAID treatment (including COX-2-inhibitors) within 2 weeks prior to the baseline visit 9. Corticosteroids except inhaled or nasal formulations for seasonal allergy or asthma are prohibited within 2 weeks prior to screening 10. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease 11. 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/1,73m²) 12. Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids 13. Evidence of active malignant disease (except basal cell carcinoma of the skin that has been excised and cured) 14. Pregnant women or nursing (breastfeeding) women 15. History of alcohol, drug, or chemical abuse within the 6 months prior to screening 16. Neuropathies or other painful conditions that might interfere with pain evaluation 17. Body weight of >150 kg 18. 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. For participants in the MRI sub-study, additional exclusion criteria apply, as specified in the protocol text.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety of AP1189 combined with MTX over 12 weeks;Secondary Objective: To compare the effects of 100 mg AP1189 against placebo;Primary end point(s): The objectives of the trial are to evaluate the efficacy and safety of AP1189 combined with MTX over 12 weeks. Primary safety endpoint: • To compare the safety of AP1189 against placebo. Safety evaluations include adverse event (AE) monitoring, physical examinations, vital sign measurements, electrocardiogram (ECG), and clinical laboratory testing (hematology, biochemistry, and urinalysis). Primary efficacy endpoint: • Effect of 100 mg AP1189 against placebo in subjects with RA, evaluated by the American College of Rheumatology 20% (ACR20) response rate at week 12 ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: To compare the effects of 100 mg AP1189 against placebo by assessing: • The American College of Rheumatology 50% (ACR50) response rate at week 12 • The American College of Rheumatology 70% (ACR70) response rate at week 12 • Time from baseline to subjects achieving American College of Rheumatology response criteria (ACR20, 50, and 70) • Change in Clinical disease activity index (CDAI) from baseline to weeks 2, 4, 8, and 12. • Change in DAS-28 (CRP) from baseline to weeks 2, 4, 8, and 12. • Percentage of subjects achieving moderate disease activity based on CDAI at weeks 2, 4, 8 and 12 • Percentage of subjects achieving low disease activity based on CDAI at weeks 2, 4, 8 and 12 • Percentage of subjects achieving disease remission based on CDAI at weeks 2, 4, 8 and 12 • Percentage of participants achieving moderate disease Activity based on DAS28(CRP) = 5.1 at weeks 2, 4, 8 and 12 • Percentage of participants achieving Low Disease Activity based on DAS28(CRP) = 3.2 at weeks 2, 4, 8 and 12 • Percentage of participants achieving disease remission based on DAS28(CRP) < 2.6 at weeks 2, 4, 8 and 12 • Proportion of patients treated with corticosteroids as rescue medication • Number of intra-articular corticosteroid injections given as rescue medication • Time from baseline to subject is treated with corticosteroid as rescue medication • Change in subject-reported quality of life (using Health Assessment Questionnaire – Disability Index (HAQ-DI)) from baseline to week 12 • Change in subject-reported fatigue (using Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue) from baseline to week 12 • Change in C-Reactive Protein (CRP) from baseline to weeks 2, 4, 8 12. ;Timepoint(s) of evaluation of this end point: Weeks 2,4, 8 and 12. | — |
Countries
Bulgaria, Moldova, Republic of
Contacts
Public ContactRegulatory Affairs
NBCD A/S
Outcome results
None listed