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Completed

NCT Number: NCT03813199

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

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.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Cliniques Universitaires Saint-Luc, Brussels, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ABX464 50mg

Drug

ABX464 is a new anti-inflammatory drug

Other names: obefazimod 50mg

Matching Placebo

Drug

placebo matching with ABX464

Other names: Placebo

ABX464 100mg

Drug

ABX464 is a new anti-inflammatory drug

Other names: obefazimod 100mg

methotrexate

Drug

MTX ≥ 10 mg/week will be given at previous dose regimen kept stable throughout the study

Other names: MTX

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

  2. 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.

  3. Change From Baseline in C-reactive Protein (CRP)

    Time frame: Week 12

    Change from baseline in C-reactive protein (CRP) at Week 12

  4. 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

  5. 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.

  6. Change From Baseline in Erythrocyte Sedimentation Rate (ESR)

    Time frame: Week 12

    Change from baseline in erythrocyte sedimentation rate (ESR) at Week 12

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

Sponsors and collaborators

Lead sponsor

Abivax S.A.

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Jan 23, 2019
Registry last updated
Feb 15, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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