Phase IIa study of ABX464 in moderate to severe active Rheumatoid Arthritis patients.

Phase 1

• Conditions: Rheumatoid Arthritis; MedDRA version: 21.1Level: LLTClassification code 10003268Term: Arthritis rheumatoidSystem Organ Class: 100000004859; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2018-004677-27-HU
• Lead Sponsor: Abivax

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-25
• Last Update Posted: 17 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified