Active, moderate to severe rheumatoid arthritis with inadequate response to methotrexate MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Cyxone AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients must give written informed consent before any trial-related assessment is performed. 2.Male or non-pregnant, non-lactating female patients at least 18 years of age. Women of childbearing potential will be screened after a confirmed menstrual period. 3.Established RA diagnosis according to the 2010 ACR/EULAR classification or the 1987 criteria. 4.Active RA (DAS28-CRP score =3.2) with at least 6 swollen joints and 6 tender joints using the 28 joint count. 5.hsCRP levels =5 mg/L at screening. 6.Patients must have taken oral or parenteral MTX 7.5-25 mg/week continuously for at least 12 weeks, with at least 6 weeks of stable dose prior to screening and throughout the duration of the trial. 7.Patients taking systemic corticosteroids must be on a stable dose of =10 mg/day prednisone or equivalent for at least 4 weeks before screening. 8.Patients taking hydroxychloroquine must be on a stable dose for at least 8 weeks before screening 9.Patients who are regularly taking Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or COX-2 inhibitors or paracetamol/acetaminophen as part of their RA therapy are required to be on a stable dose for at least 4 weeks before screening. 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 91 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 69
Exclusion criteria
Exclusion criteria: 1.RA patients functional status class IV classified according to the ACR 1991 revised criteria. 2.Patients taking high potency opioid. 3.Use of strong CYP3A4 inhibitors within 2 weeks prior to screening and during the trial. 4.Previous long-term use of TNFa, T-cell co stimulation inhibition, IL-6 receptor blockers, anti B-cell therapy and Janus Kinase inhibitors. 5.Any therapy by intra-articular and intramuscular injections within 4 weeks before screening. 6.Treatment with hydroxychloroquine at a dose >5 mg/kg/day for >5 years 7.Pregnant or nursing women. 8.Women of child-bearing potential unless: a) Women who observe total abstinence when this is in line with the preferred and usual lifestyle of the patient during the trial participation until 58 days from the last dose of the study drug. b) Women whose partners have been sterilized by vasectomy or other means. c) Women using a highly effective method of birth control. 9.Male patients must be using two acceptable methods of contraception for the entire duration of the trial, up to the End of Treatment visit and refrain from fathering a child in the at least 118 days months following the last IMP administration. Vasectomised partner is a highly effective birth control method. 10.Inflammatory diseases other than RA that might confound the evaluation of the benefit of rabeximod therapy. 11.Laboratory evidence of underlying metabolic, haematologic, renal, hepatic, pulmonary, neurologic, endocrine, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk. 12.Recent myocardial infarction, coronary revascularization, or percutaneous angioplasty; acute coronary syndrome; chronic uncompensated heart failure or New York Heart Association Functional Class III or IV; left ventricular assist devices; implanted defibrillators. 13.History of clinically significant alcoholic liver disease or liver. 14.History of severe chronic renal insufficiency, or patients with one kidney, or a creatinine level exceeding 1.5 mg/dL. 15.Screening total whole blood cell count <3,000/µL, or platelets <100,000/µL or neutrophils <1,500/µL or hemoglobin <8.5 g/dL. 16.Active systemic infections during the last two weeks prior to screening. 17.Infection with tuberculosis, HIV, hepatitis B or hepatitis C by a positive test at screening: a) Patients with positive or indeterminate tuberculosis test at screening can be eligible if they have all of the following: - No clinical features of active tuberculosis. - Completed appropriate treatment for active or latent tuberculosis. - No history of re-exposure since their treatment was completed. - Chest x-ray with no evidence of active tuberculosis. b) If the HIV test result is positive, the patient cannot be enrolled. c) At Screening: - If the HBsAg test result is positive, the patient cannot be enrolled. - If a patient has results of HBsAg (negative), HBsAb (negative or positive), and HBcAb (positive), a hepatitis B virus (HBV) DNA test will be performed at Screening. •If the HBV DNA test result is positive, the patient cannot be enrolled. •If the HBV DNA test result is negative and the patient does not have any evidence of liver cirrhosis, the patient can be enrolled. d) At Screening: - If the HCV RNA test result is positive, the patient cannot be enrolled. - If the HCA result is positive and HCV RNA test result is negative, the patient can be enrolled as long as the pa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To assess the efficacy (measured by DAS28-CRP) of rabeximod compared to placebo as add-on therapy in patients with active, moderate to severe RA with inadequately controlled disease;Secondary Objective: -To assess the efficacy (measured by ACR20/ACR50/ACR70) of rabeximod compared to placebo as add-on therapy in patients with active, moderate to severe RA with inadequately controlled disease. -To assess the safety and tolerability of rabeximod compared to placebo as add-on therapy in patients with active, moderate to severe RA with inadequately controlled disease. -To assess the effect of rabeximod compared to placebo as add-on therapy in patients with active, moderate to severe RA with inadequately controlled disease on health-related quality of life (HRQoL). ;Primary end point(s): Change from baseline in DAS28-CRP at Week 16;Timepoint(s) of evaluation of this end point: Week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoint -Change from baseline in DAS28-CRP at Week 12 Other Secondary Efficacy Endpoints -Change from baseline in DAS28-CRP at Week 4, 8, 20, and 24 -Clinical response to treatment based on an improvement of DAS28-CRP of >1.2 at Weeks 4, 8, 12, 16, 20, and 24 as compared to baseline -Clinical response to treatment based on DAS28-CRP <3.2 at Weeks 12, 16, and 24 -Clinical remission based on DAS28-CRP <2.6 at Weeks 12, 16, and 24 -Clinical response to treatment according to ACR20, ACR50 and ACR70 individual improvement in disease activity at Week 12, 16, and 24 as compared to baseline. A patient will be considered a responder according to the ACR criteria if he/she has at least: -20%, 50% or 70% improvement in tender 28-joint count -20%, 50% or 70% improvement in swollen 28-joint count -and 20%, 50% or 70% improvement in at least 3 of the following 5 measures: 1.Patient’s assessment of arthritis pain (visual analogue scale [VAS] 100 mm) 2.Patient’s global assessment of disease activity (VAS 100 mm) 3.Physician’s global assessment of disease activity (VAS 100 mm) 4.Patient self-assessed disability (HAQ-DI) score 5.Acute phase reactant (hsCRP) -ACR components at Weeks 12, 16 and 24 oChange from baseline in tender 28-joint count oChange from baseline in swollen 28-joint count oChange from baseline in hsCRP oChange from baseline in erythrocyte sedimentation rate (ESR) -Change from baseline in HAQ-DI at Weeks 16 and 24 -Patient’s assessment of arthritis pain (VAS 100 mm) at Weeks 4, 8, 12, 16, 20 and 24 -Patient’s global assessment of disease activity (VAS 100 mm) at Weeks 4, 8, 12, 16, 20 and 24 -Physician’s global assessment of disease activity (VAS 100 mm) at Weeks 4, 8, 12, 16, 20 and 24;Timepoint(s) of evaluation of this end point: See above, timepoints added to each single end point | — |
Countries
Bosnia and Herzegovina, Bulgaria, Georgia, Hungary, Moldova, Republic of, Poland, Serbia, United States
Contacts
Public ContactCarl Magnus Högerkorp- CEO
Cyxone AB
Outcome results
None listed