Study of Two Doses of ABX464 in Participants With Moderate to Severe Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT03813199
• Recruitment Status: Completed
• First Posted: January 23, 2019
• Results First Posted: April 7, 2022
• Last Update Posted: February 15, 2023
• Sponsor: Abivax S.A.
• Information provided by (Responsible Party): Abivax S.A.

Tracking Information

• First Submitted Date: January 15, 2019
• First Posted Date: January 23, 2019
• Results First Submitted Date: February 3, 2022
• Results First Posted Date: April 7, 2022
• Last Update Posted Date: February 15, 2023
• Actual Study Start Date: July 4, 2019
• Actual Primary Completion Date: April 27, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2023)

Number of Treatment-emergent Adverse Events in the ABX464 Treated Patients Versus Placebo [ Time Frame: through study completion, an average of 15 weeks ]

TEAE definition is undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment

• Original Primary Outcome Measures (submitted: January 18, 2019): Incidence of treatment-emergent adverse events in the ABX464 treated Patients versus placebo, categorized by severity [ Time Frame: through study completion, an average of 15 weeks ]

Current Secondary Outcome Measures (submitted: February 10, 2023)

• Number of Patients Achieving ACR20 Response [ Time Frame: at Week 12 ]
  The categorical American College of Rheumatology 20% (ACR20) response is a validated index of rheumatoid arthritis disease activity, defined by the number of patients who achieved at least 20% improvement in the ACR response.
• Number of Patients Achieving ACR20/50/70 Response [ Time Frame: Week 12 ]
  Number of patients who achieved at least 20%, 50% or 70% improvement in the American College of Rheumatology (ACR) response.
• Change From Baseline in C-reactive Protein (CRP) [ Time Frame: Week 12 ]
  Change from baseline in C-reactive protein (CRP) at Week 12
• Number of Patients Achieving DAS28-CRP Response [ Time Frame: Week 12 ]
  Number 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
• Change From Baseline in Disease Activity Scores (DAS-CRP) (28 Joints) [DAS28] [ Time Frame: Week 12 ]
  The DAS28 is a validated index of rheumatoid arthritis disease activity. The DAS28 assessment include 28 tender and swollen joint counts (TJC and SJC), acute phase reactant (CRP ), and patient's global assessment of disease activity (PtGA). DAS28-CRP = 0.56 √ (TJC28) + 0.28 √ (SJC28) + 0.36 Ln [CRP(mg/L)+1] + 0.014 PtGA(VAS100mm) + 0.96 Score scale range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.
• Change From Baseline in Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Week 12 ]
  Change from baseline in erythrocyte sedimentation rate (ESR) at Week 12
• Number of Patients Achieving Disease Activity Score (DAS) DAS28-Erythrocyte Sedimentation Rate (ESR) [DAS28-ESR] Remission [ Time Frame: Week 12 ]
  Number of patients achieving Disease Activity Score (DAS) DAS28-Erythrocyte Sedimentation Rate (ESR) [DAS28-ESR]remission, which is defined as DAS2-ESR < 2.6
• Change From Baseline in Disease Activtiy Score (DAS)28-Erythrocyte Sedimentation Rate (ESR) [ Time Frame: 12 weeks ]
  The DAS28 is a validated index of rheumatoid arthritis disease activity. The DAS28 assessment include 28 tender and swollen joint counts (TJC and SJC), acute phase reactant (ESR), and patient's global assessment of disease activity (PtGA). DAS28-ESR = 0.56 √ (TJC28) + 0.28 √ (SJC28) + 0.70 Ln [ESR(mm/h)] + 0.014 PtGA(VAS100mm) Score scale range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. change from baseline at weeks 12: the bigger negative score shows a bigger improvment
• Change From Baseline in Simplified Disease Activity Index Score (SDAI) [ Time Frame: Week 12 ]
  SDAI is a validated index of rheumatoid arthritis disease activity. The SDAI calculation is based on 28 tender and swollen joint counts, C-Reactive Protein (CRP), patient's global assessment of disease activity (PtGA) and physician's global assessment of disease activity (PrGA). SDAI score= tender28 + swollen28 + CRP + (PtGA/10) + (PrGA/10). A moderate activity is defined by a SDAI score >11 to 26 included. A high activity is defined by a SDAI score >26. Change from Baseline: the higher negative number shows a bigger improvment
• Change From Baseline in Clinical Disease Activity Index Score (CDAI) [ Time Frame: Week 12 ]
  CDAI is a validated index of rheumatoid arthritis disease activity. The CDAI calculation is based on 28 tender and swollen joint counts, patient's global assessment of disease activity (PtGA) and physician's global assessment of disease activity (PrGA). CDAI score= tender28 + swollen28 + (PtGA/10) + (PrGA/10). A moderate activity is defined by a CDAI score >10 to 22 included. A high activity is defined by a CDAI score >22. Change from Baseline: the higher negative number shows a bigger improvment
• Number of Patients Achieving Low Disease Activity (LDA) [ Time Frame: Week 12 ]
  Number of patients achieving a Low Disease Activity (LDA) which is defined as DAS28-ESR <=3.2
• Number of Patients Achieving Simplified Disease Activity Score (SDAI) Remission [ Time Frame: Week 12 ]
  Number of patients achieving Simplified Disease Activity Score (SDAI) remission, which is considered achieved if the SDAI score ≤ 3.3
• Number of Patients Achieving Clinical Disease Activity (CDAI) Remission [ Time Frame: Week 12 ]
  Number of patients achieving Clinical Disease Activity (CDAI) remission, which is considered achieved if the CDAI score ≤ 2.8
• Number of Patients Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission [ Time Frame: Week 12 ]
  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
• Change From Baseline in Tender/Painful Joint Count (TJC28) [ Time Frame: 12 weeks ]
  Change from Baseline in Tender/painful joint count based on 28-joint assessment (TJC28) at Week 12 TJC28 score range from 0 to 28 Change from Baseline: the higher the negative number is, the better improvment is
• Change From Baseline in Swollen Joint Count (SJC) [ Time Frame: 12 weeks ]
  Change from Baseline in Swollen joint count based on 28-joint assessment (SJC28) at Week 12 SJC28 score range from 0 to 28 Change from Baseline: the higher the negative number is, the better improvment is
• Change From Baseline in Pain Visual Analog Scale [ Time Frame: 12 weeks ]
  Change from Baseline in Pain Visual Analog Scale (Pain-VAS) at week 12 The VAS range from 0 to 10 cm (the higher, the more painful) A bigger negative change from baseline shows a bigger improvment
• Change From Baseline in Patient Global Assessment of Disease (PtGA) [ Time Frame: 12 weeks ]
  Change from Baseline in Patient Global Assessment of Disease (PtGA) . This is a patient's self assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity The change from baseline: a bigger negative number shows a bigger improvment
• Change From Baseline in Investigator Global Assessment of Disease (PrGA) [ Time Frame: 12 weeks ]
  Change from Baseline in Investigator global assessment of disease (PrGA): investigator's assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity The change from baseline: the higher negative number shows a better improvement
• Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: 12 weeks ]
  Change from Baseline in Health Assessment questionnaire disability index (HAQ-DI) at Week 12 There are 8 sections in this questionnaire: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). For each section the score given to that section is the worst score within the section, i.e. if one question is scored 1 and another 2, then the score for the section is 2. In addition, if an aide or device is used or if help is required from another individual, then the minimum score for that section is 2. The 8 scores of the 8 sections are summed and divided by the number of section answered. This gives a score range from 0 to 3 (the bigger the worst activity). The change from Baseline: the bigger negative number shows a bigger improvment

Original Secondary Outcome Measures (submitted: January 18, 2019)

• Proportion of patients achieving ACR20 response [ Time Frame: at Week 12 ]
  The categorical American College of Rheumatology 20% (ACR20) response is a validated index of rheumatoid arthritis disease activity, defined by the number of patients who achieved at least 20% improvement in the ACR response.
• Change from baseline in the individual components of ACR response [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  American College of Rheumatology (ACR) criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.
• Change from baseline in erythrocyte sedimentation rate (ESR) [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
• Change from baseline in Disease Activity Scores (DAS) (28 joints) [DAS28] [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  The DAS28 is a validated index of rheumatoid arthritis disease activity. The DAS28 assessment include 28 tender and swollen joint counts (TJC and SJC), acute phase reactant (CRP or ESR), and patient's global assessment of disease activity (PtGA). DAS28-ESR = 0.56 √ (TJC28) + 0.28 √ (SJC28) + 0.70 Ln [ESR(mm/h)] + 0.014 PtGA(VAS100mm) DAS28-CRP = 0.56 √ (TJC28) + 0.28 √ (SJC28) + 0.36 Ln [CRP(mg/L)+1] + 0.014 PtGA(VAS100mm) + 0.96 Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.
• Change from baseline in Simplified Disease Activity Index Score (SDAI) [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  SDAI is a validated index of rheumatoid arthritis disease activity. The SDAI calculation is based on 28 tender and swollen joint counts, C-Reactive Protein (CRP), patient's global assessment of disease activity (PtGA) and physician's global assessment of disease activity (PrGA). SDAI = tender28 + swollen28 + CRP + (PtGA/10) + (PrGA/10). A moderate activity is defined by a SDAI >11 to 26 included. A high activity is defined by a SDAI >26.
• Change from baseline in Clinical Disease Activity Index Score (CDAI) [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  CDAI is a validated index of rheumatoid arthritis disease activity. The CDAI calculation is based on 28 tender and swollen joint counts, patient's global assessment of disease activity (PtGA) and physician's global assessment of disease activity (PrGA). CDAI = tender28 + swollen28 + (PtGA/10) + (PrGA/10). A moderate activity is defined by a CDAI >10 to 22 included. A high activity is defined by a CDAI >22.
• Proportion of patients achieving ACR20/50/70 response [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  Proportion of patients who achieved at least 20%, 50% or 70% improvement in the American College of Rheumatology (ACR) response.
• Proportion of patients achieving DAS28-CRP response [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  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
• Proportion of patients achieving Low Disease Activity (LDA) [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  Low Disease Activity (LDA) is defined as DAS28-ESR <=3.2
• Proportion of patients achieving Disease Activity Score (DAS) DAS28-Erythrocyte Sedimentation Rate (ESR) [DAS28-ESR] remission [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  DAS28-ESR remission is defined as DAS2-ESR < 2.6
• Proportion of patients achieving Simplified Disease Activity Score (SDAI) remission [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  The SDAI remission is considered achieved if the SDAI score ≤ 3.3
• Proportion of patients achieving Clinical Disease Activity (CDAI) remission [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  The CDAI remission is considered achieved if the CDAI score ≤ 2.8
• Proportion of patients achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• Drug: ABX464 50mg
  ABX464 is a new anti-inflammatory drug
  Other Name: obefazimod 50mg
• Drug: Matching Placebo
  placebo matching with ABX464
  Other Name: Placebo
• Drug: ABX464 100mg
  ABX464 is a new anti-inflammatory drug
  Other Name: obefazimod 100mg
• Drug: Methotrexate
  MTX ≥ 10 mg/week will be given at previous dose regimen kept stable throughout the study
  Other Name: MTX

Study Arms

• Experimental: ABX464 50mg + methotrexate

  Participants will receive one capsule of 50mg ABX464 plus one capsule of matching placebo once daily for 12 weeks

  + methotrexate

  Interventions:

  • Drug: ABX464 50mg
  • Drug: Matching Placebo
  • Drug: Methotrexate
• Experimental: ABX464 100mg + methotrexate

  Participants will receive two capsules of 50mg ABX464 once daily for 12 weeks

  + methotrexate

  Interventions:

  • Drug: ABX464 100mg
  • Drug: Methotrexate
• Placebo Comparator: Placebo + methotrexate

  Participants will receive two capsules of matching placebo once daily for 12 weeks

  + methotrexate

  Interventions:

  • Drug: Matching Placebo
  • Drug: Methotrexate

• Publications *: 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 May 31;81(8):1076-84. doi: 10.1136/annrheumdis-2022-222228. Online ahead of print.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 18, 2019): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 27, 2021
• Actual Primary Completion Date: April 27, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, France, Hungary, Poland

Administrative Information

• NCT Number: NCT03813199
• Other Study ID Numbers: ABX464-301
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Abivax S.A.
• Original Responsible Party: Same as current
• Current Study Sponsor: Abivax S.A.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Paul GINESTE, PharmD; Abivax S.A.

• PRS Account: Abivax S.A.
• Verification Date: May 2022