Study Evaluating the Long-Term Safety and Efficacy of ABX464 in Patients With Moderate to Severe Rheumatoid Arthritis

This Phase 2a open-label study aims at investigating the long-term safety and efficacy of an oral dose of ABX464 in patients who have been previously enrolled in the ABX464-301 clinical study and who are willing to continue their treatment.

All patients will receive ABX464 given at 50mg o.d. irrespectively of their previous treatment received in the ABX464-301 study (i.e. ABX464 or Placebo).

The enrolment in this follow-up study will be based on the willingness of the subject to carry on his/her participation and also based on investigator's judgement.

Patients will be treated with ABX464 for a period of 52 weeks. If they achieve a clinical response on Week 52 (defined as DAS28-CRP ≤ 2,6 for anti-TNFα naïve patients or DAS-28-CRP ≤ 3,2 for patients previously treated by anti-TNFα), they will be eligible to continue treatment for up to 104 weeks.Patients will be followed up at week , week 2 and then, on a monthly basis the first year (up to W52), and quaterly the second year (up to W104).

• ABX464 (Drug): All subjects will receive ABX464 administered at 50 mg o.d for an overall period of 2 years (104 weeks).

Primary outcomes

• Incidence of treatment-emergent adverse events in the ABX464 treated Patients, categorized by severity [through study completion (average of 104 weeks)]: Incidence of adverse events emerging during the treatment

Secondary outcomes

• Proportion of patients achieving Low Disease Activity (LDA) [Week 4, Week 12, Week 24, Week36, Week 52, Week 65, Week 78, Week 91 and Week 104]: Low Disease Activity (LDA) is defined as DAS28-ESR <=3.2
• Proportion of patients achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission [Week 4, Week 12, Week24, Week36, Week 52, Week 65, Week 78, Week 91 and Week 104]: The ACR/EULAR boolean-based remission is a validated criteria based on: Tender/painful Joint Count (28), Swollen Joint Count (28), C-Reactive Protein, patient global assessment of disease, All ≤ 1
• Proportion of patients achieving Simplified Disease Activity Score (SDAI) remission [Week 4, Week 12, Week 24, Week36, Week 52, Week 65, Week 78, Week 91 and Week 104]: The SDAI remission is considered achieved if the SDAI score ≤ 3.3
• Proportion of patients achieving Clinical Disease Activity (CDAI) remission [Week 4, Week 12, Week 24, Week36, Week 52, Week 65, Week 78, Week 91 and Week 104]: The CDAI remission is considered achieved if the CDAI score ≤ 2.8
• Proportion of patients achieving ACR20/50/70 response [Week 4, Week 12, Week 24, Week36, Week 52, Week 65, Week 78, Week 91 and Week 104]: The categorical American College of Rheumatology 20% or 50% or 70% (ACR20/50/70) response is a validated index of rheumatoid arthritis disease activity, defined by the number of patients who achieved at least 20% or 50% or 70% improvement in the ACR response.
• Proportion of patients achieving categorical Disease Activity Scores (DAS) (measured on 28 joints) - C-Reactive Protein (DAS28-CRP) response [Week 4, Week 12, Week 24, Week36, Week 52, Week 65, Week 78, Week 91 and Week 104]: Proportion of patients achieving categorical Disease Activity Score (DAS) DAS28-C-Reactive Protein (CRP) \[DAS28-CRP\] response will be measured as moderate/good European League Against Rheumatism (EULAR) response
• Time to onset of the Low Disease Activity (LDA) remission [up to 104 weeks]: time when DAS28-ESR <=3.2
• Time to onset of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission [up to 104 weeks]: The ACR/EULAR remission is a validated criteria based on: Tender/painful Joint Count (28), Swollen Joint Count (28), C-Reactive Protein, patient global assessment of disease, All ≤ 1. Time to onset will be when this criteria will be ≤ 1

Sex: All, ages: 18 Years to 76 Years

Inclusion Criteria:

* Patients previously enrolled in the ABX464-301 clinical study who have completed the initial 12 weeks of treatment period;

Criteria that should be met by patients at week 52 to be eligible for 52 additional weeks of study treatment:

▪ Patients should be in clinical response. Clinical response is defined as: DAS28-CRP ≤ 2,6 for anti-TNFα naïve patients or DAS-28-CRP ≤ 3,2 for patients previously treated by anti-TNFα.

Exclusion Criteria:

* Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol

• Laurence Desroys du Roure, PharmD, Study chair, Abivax S.A.