Clinical trial NCT03813199: Study of Two Doses of ABX464 in Participants With Moderate to Severe Rheumatoid Arthritis
Official title: Phase IIa Randomized, Double Blind, Placebo Controlled, Multiple Dose Study on ABX464 in Combination With Methotrexate (MTX), in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have Inadequate Response to MTX or/and to Anti-Tnfα, or Intolerance to Anti-Tnfα
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Abivax S.A.
Sponsor class: INDUSTRY
First posted: 2019-01-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase IIa study aims at investigating the safety and tolerability of 2 dose-levels of ABX464 administered daily in combination with methotrexate (MTX) in patients with moderate to severe active Rheumatoid Arthritis (RA) who had an inadequate response to MTX or/and to one or more anti- tumor necrosis factor alpha (TNFα) therapies.

Detailed description: This is a randomized, double-blind, placebo-controlled, multicenter study. The study will consist of 3 phases: a screening phase, a treatment phase, and a follow-up phase.

Approximately 60 participants with active Rheumatoid Arthritis will be randomly assigned to receive placebo, 50mg ABX464 or 100mg ABX464 during the treatment phase.

The maximum period of active treatment will be 12 weeks. The maximum duration of study participation will be 17 weeks.

Participant safety will be monitored throughout the study. In addition, several experimental and clinical endpoints will be assessed to obtain information on preliminary efficacy.

Eligibility criteria: Inclusion Criteria:

* Patient with a confirmed and documented diagnosis of adult-onset rheumatoid arthritis, for at least 12 weeks, according to the revised 2010 American College of Rheumatology- European League Against Rheumatism (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 (SJC) of ≥ 4 (28-joint count) and tender joint count (TJC) ≥4 (28-joint count) at screening;
* Patient with a moderate to severe disease activity score Disease Activity Score (28 joints) C-Reactive Protein \[DAS28 CRP\] ≥ 3.2 and C-reactive Protein (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- Tumor Necrosis Factor alpha (TNFα) therapy (both administered for at least 12 weeks before IR) or were intolerant to anti- TNFα therapy.

Exclusion Criteria:

* 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 CytoMegaloVirus (CMV), herpes virus and/or recent infectious hospitalization;
* Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable Central Nervous System (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 non-anti-TNF biological Disease-Modifying AntiRheumatic Drugs (bDMARDs), and targeted DMARDs (tDMARDS) prior to baseline.

Primary outcomes:
measure: Number of Treatment-emergent Adverse Events in the ABX464 Treated Patients Versus Placebo
timeFrame: through study completion, an average of 15 weeks
Secondary outcomes:
measure: Number of Patients Achieving ACR20 Response
timeFrame: at Week 12
measure: Number of Patients Achieving ACR20/50/70 Response
timeFrame: Week 12
measure: Change From Baseline in C-reactive Protein (CRP)
timeFrame: Week 12
measure: Number of Patients Achieving DAS28-CRP Response
timeFrame: Week 12
measure: Change From Baseline in Disease Activity Scores (DAS-CRP) (28 Joints) [DAS28]
timeFrame: Week 12
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Week 12
measure: Number of Patients Achieving Disease Activity Score (DAS) DAS28-Erythrocyte Sedimentation Rate (ESR) [DAS28-ESR] Remission
timeFrame: Week 12
measure: Change From Baseline in Disease Activtiy Score (DAS)28-Erythrocyte Sedimentation Rate (ESR)
timeFrame: 12 weeks
measure: Change From Baseline in Simplified Disease Activity Index Score (SDAI)
timeFrame: Week 12
measure: Change From Baseline in Clinical Disease Activity Index Score (CDAI)
timeFrame: Week 12
measure: Number of Patients Achieving Low Disease Activity (LDA)
timeFrame: Week 12
measure: Number of Patients Achieving Simplified Disease Activity Score (SDAI) Remission
timeFrame: Week 12
measure: Number of Patients Achieving Clinical Disease Activity (CDAI) Remission
timeFrame: Week 12
measure: Number of Patients Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission
timeFrame: Week 12
measure: Change From Baseline in Tender/Painful Joint Count (TJC28)
timeFrame: 12 weeks
measure: Change From Baseline in Swollen Joint Count (SJC)
timeFrame: 12 weeks
measure: Change From Baseline in Pain Visual Analog Scale
timeFrame: 12 weeks
measure: Change From Baseline in Patient Global Assessment of Disease (PtGA)
timeFrame: 12 weeks
measure: Change From Baseline in Investigator Global Assessment of Disease (PrGA)
timeFrame: 12 weeks
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Merksem
country: Belgium
facility: ZNA Jan Palfijn
city: Praha
country: Czechia
facility: Fakultni Tomayerova nemocnice
city: Praha
country: Czechia
facility: Revmatologicky ustav
city: Brest
country: France
facility: CHU de Brest - Hôpital Cavale Blanche
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Montpellier
country: France
facility: CHU de Montpellier - Lapeyronie
city: Mulhouse
country: France
facility: GHR Mulhouse Sud-Alsace
city: Nice
country: France
facility: CHU de Nice - Hôpital Pasteur
city: Orléans
country: France
facility: CHR d'Orléans
city: Paris
country: France
facility: APHP - Hôpital Salpétrière
city: Tours
country: France
facility: CHU de Tours - Hôpital Trousseau
city: Budapest
country: Hungary
facility: Complex Medical Centre - Déli Klinika
city: Miskolc
country: Hungary
facility: CRU Hungary Ltd.
city: Székesfehérvár
country: Hungary
facility: CMed Rehabilitációs és Diagnosztikai Központ
city: Białystok
country: Poland
facility: ClinicMed Daniluk, Nowak Sp. J.
city: Kraków
country: Poland
facility: Pratia MCM
city: Lublin
country: Poland
facility: Zespół Poradni Specjalistycznych REUMED
city: Nadarzyn
country: Poland
facility: NZOZ Lecznica MAK-MED S.C.
city: Poznań
country: Poland
facility: Medyczne Centrum Hetmańska
city: Warszawa
country: Poland
facility: National Institute of Geriatrics
city: Warszawa
country: Poland
facility: RHEUMA MEDICUS Zakład Opieki Zdrowotnej
Study officials:
affiliation: Abivax S.A.
name: Paul GINESTE, PharmD
role: STUDY_DIRECTOR
References:
citation: Daien C, Krogulec M, Gineste P, Steens JM, Desroys du Roure L, Biguenet S, Scherrer D, Santo J, Ehrlich H, Durez P. Safety and efficacy of the miR-124 upregulator ABX464 (obefazimod, 50 and 100 mg per day) in patients with active rheumatoid arthritis and inadequate response to methotrexate and/or anti-TNFalpha therapy: a placebo-controlled phase II study. Ann Rheum Dis. 2022 Jul 12;81(8):1076-1084. doi: 10.1136/annrheumdis-2022-222228.