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

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ClinicalTrials.gov Identifier: NCT03813199
Recruitment Status : Recruiting
First Posted : January 23, 2019
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Abivax S.A.

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: ABX464 50mg Drug: Matching Placebo Drug: ABX464 100mg Drug: Methotrexate Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IIa Randomized, Double Blind, Placebo Controlled, Parallel Group, 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 an Anti- Tumor Necrosis Factor Alpha (Tnfα) Therapy, or Intolerance to Anti-Tnfα Therapy
Actual Study Start Date : July 4, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ABX464 50mg + methotrexate

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

+ methotrexate

Drug: ABX464 50mg
ABX464 is a new anti-inflammatory drug

Drug: Matching Placebo
placebo matching with ABX464

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

Experimental: ABX464 100mg + methotrexate

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

+ methotrexate

Drug: ABX464 100mg
ABX464 is a new anti-inflammatory drug

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

Placebo Comparator: Placebo + methotrexate

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

+ methotrexate

Drug: Matching Placebo
placebo matching with ABX464

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




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Change from baseline in erythrocyte sedimentation rate (ESR) [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
  4. 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.


  5. 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.


  6. 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.


  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03813199


Contacts
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Contact: Paul GINESTE, PharmD +33 1 5383 0961 paul.gineste@abivax.com
Contact: Jean-Marc STEENS, MD +33 1 5383 0961 Jean-marc.steens@abivax.com

Locations
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France
CHU de Montpellier - Lapeyronie Recruiting
Montpellier, France, 34000
Contact: DAIEN Claire, MD         
Sponsors and Collaborators
Abivax S.A.
Investigators
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Study Director: Paul GINESTE, PharmD Abivax S.A.

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Responsible Party: Abivax S.A.
ClinicalTrials.gov Identifier: NCT03813199     History of Changes
Other Study ID Numbers: ABX464-301
First Posted: January 23, 2019    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors