Rheumatoid Arthritis MedDRA version: 21.1 Level: LLT Classification code 10003268 Term: Arthritis rheumatoid System Organ Class: 100000004859
Conditions
Sponsors
Abivax
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be eligible for inclusion in this study only if ALL of the following criteria apply: - Men or women age 18 - 75 years; - Patient with a confirmed and documented diagnosis of adult-onset rheumatoid arthritis, for at least 12 weeks, according to the revised 2010 ACR-EULAR classification criteria, including at least one positive criteria among the following: Rheumatoid Factor (RF), Anti-Citrullinated Peptide Antibody (ACPA) or bone erosion; - Swollen joint count of = 4 (28-joint count) and tender joint count =4 (28-joint count) at screening; - Patient with a moderate to severe disease activity score DAS28 CRP of = 3.2 and CRP = 5 mg/L (= 4.76 nmol)/L) at screening; - Patient who had an inadequate response (IR), or failed either methotrexate (MTX) or/and anti-TNFa therapy (both administered for at least 12 weeks before IR) or were intolerant to anti- TNFa therapy. In addition, MTX treatment should be given at a stable dose = 10 mg/week (for at least 4 weeks prior to randomization) and associated with folic acid = 10 mg/week. For the anti-TNFa therapy, the following wash-out period will be required: o 30 days prior to randomization for adalimumab and etanercept o 2 months prior to randomization for infliximab, certolizumab pegol, golimumab - Patients with the following hematological and biochemical laboratory parameters obtained within 14 days prior to baseline: o Hemoglobin > 9.0 g dL-1; o Absolute neutrophil count = 1000 mm-3; o Platelets = 100,000 mm-3; o Total serum creatinine = 1.3 x ULN (upper limit of normal); o Creatinine clearance > 50 mL min-1 by the Cockcroft-Gault equation within 60 days prior to baseline; o Total serum bilirubin < 1.5 x ULN; o Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 1.5 x ULN; o Negative screening for TB (or if positive, the use of anti-TB prophylaxis according to recommendation) and HIV, HCV, HBV - Patients are able and willing to comply with study visits and procedures as per protocol; - Patients should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures are performed; - Patients should be affiliated to a social security regimen (for French sites only); - Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination. Contraception should be in place at least 2 weeks prior to screening. Women must be surgically sterile or if of childbearing potential must use a highly effective contraceptive method. Women of childbearing potential (WOCBP) will enter the study after confirmed menstrual period and a negative pregnancy test. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) or hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing system, bilateral tubal ligation, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the patient. In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is required. This recommendation also applies to WOCBP with infrequent or irregular menstrual cycle. Female and male patients must not be planning pregnancy and male patients should use condom and must not donate sperm must not donate sperm during the trial and for 3 months post completion of their
Exclusion criteria
Exclusion criteria: The following criteria should be checked at the time of screening. If ANY exclusion criterion applies, the patient will not be included in the study: - Patient with a known positive anti-double stranded deoxyribonucleic acid (DNA [anti-dsDNA]) and confirmed diagnosis of systemic lupus erythematosus (SLE); - Patient with known active infections at screening such as CMV, herpes and/or recent infectious hospitalization; - Acute, chronic or history of clinically relevant (as per investigator’s judgement) pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable CNS pathology such as seizure disorder, angina or cardiac arrhythmias, active malignancy or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history; - Acute, chronic or history of immunodeficiency or other autoimmune disease; - Patient previously treated with any (approved or investigational) non-anti-TNF biological disease-modifying antirheumatic drugs (bDMARDs), and targeted DMARDs (tDMARDS) prior to baseline. These treatments include: IL-6 antagonists, Janus Kinase (JAK) inhibitors, cytotoxic T lymphocyte-associated molecule CTLA-4Fc Chimera, rituximab; - Patient treated with systemic corticosteroids >10 mg/day during the 2 weeks prior to and at randomization; IV or IM injections of glucocorticoids 4 weeks prior to randomization and IA glucocorticoids 2 weeks prior to randomization; - Patients treated with other immunosuppressive drugs; - History of malignancy (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence) unless it has been treated and a cure is achieved for at least 5 years; - Serious illness requiring systemic treatment and/or hospitalization within 3 weeks prior to baseline; - Pregnant or breast-feeding woman; - Illicit drug or alcohol abuse or dependency; - Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer - Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the safety of ABX464 given at two different doses (100mg and 50 mg) vs placebo in combination with MTX when administered once daily in patients with moderate to severe active Rheumatoid Arthritis.;Secondary Objective: To evaluate the effects of the different dose groups of ABX464 at Weeks 2, 4, 8 and 12 on the American College of Rheumatology (ACR) 20/50/70 response and each of its components versus placebo; To evaluate the effects of the different dose groups of ABX464 at Weeks 2, 4, 8 and 12 on disease activity scores (DAS28 scores, simplified disease activity score [SDAI] and clinical disease activity score [CDAI]) versus placebo; To evaluate the effects of the different dose groups of ABX464 at Weeks 2, 4, 8 and 12 on clinical response (DAS28 EULAR good and moderate responses), Low Disease Activity (LDA) or remission (DAS28-ESR remission, ACR/EULAR remission, SDAI and CDAI remission) versus placebo; To evaluate the effects of the different dose groups of ABX464 at Weeks 2, 4, 8 and 12 on the (PRO) & (HAQ-DI); To assess the PK of the ABX464 and its main active metabolite N-Glu-ABX464 after oral administration of different daily doses of ABX464 in patients with rheumatoid Arthritis.;Primary end point(s): The primary endpoint is the incidence of treatment-emergent adverse events in the ABX464 treated Patients versus placebo, categorized by severity.;Timepoint(s) of evaluation of this end point: Timepoint of evaluation of this end point from day 0 to EoS. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: Main Efficacy Endpoint: Proportion of patients achieving a categorical ACR20 response at Week 12. The components of ACR20 assessment include: o C-Reactive Protein (CRP) (mg/L), o Tender/painful joint count (TJC) (28 joints), o Swollen joint count (SJC) (28 joints), o Patient assessment of joint pain (Pain-VAS), o Patient global assessment of disease (PtGA), o Physician's Global Assessment of Disease (PrGA), o Disability index of the healthy assessment questionnaire (HAQ-DI) Other secondary endpoints: Change from Baseline in the following disease parameters at Week 2, Week 4, Week 8 and Week 12: o Individual components of the ACR20 response (CRP, TJC(28), SJC(28), Pain-VAS, PtGA, PrGA, HAQ-DI); o Erythrocyte Sedimentation Rate (ESR); o DAS28-CRP and DAS28-ESR. The components of DAS28 assessment include TJC(28), SJC(28), CRP/ESR, and PtGA; o SDAI score which includes TJC(28), SJC(28), CRP, PtGA, and PrGA; o CDAI score which includes TJC(28), SJC(28), PtGA, and PrGA; o FACIT-Fatigue score. • Proportion of patients achieving at Week 2, Week 4, Week 8 and Week 12: o ACR20/50/70 response o Categorical DAS28-CRP response. Proportion of patients achieving categorical DAS28-CRP response will be measured as moderate/good European League Against Rheumatism (EULAR) response at each assessment time point; o Low Disease Activity (LDA) (DAS28 = 3.2) o DAS28-ESR remission (DAS28 < 2.6) o ACR/EULAR remission (TJC(28), SJC(28), CRP, and PtGA: all=1); o SDAI remission (SDAI = 3.3); o CDAI remission (CDAI = 2.8). PK parameters: o Pre-dose plasma concentration of ABX464/N-Glu at Week 2 and Week 8; o Post-dose plasma concentration of ABX464/N-Glu at 1-, 2- and 3-hours post-dose at Baseline, Week 2 and Week 8; o Trough plasma concentration of ABX464/N-Glu at End of Study Visit The number of incidences of treatment-emergent serious adverse events (through the whole study) The number of incidences of treatment-emergent adverse events | — |
Countries
Belgium, Hungary
Contacts
Public ContactVP Clinical Operations
Abivax
Outcome results
None listed