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

Abivax S.A.60 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Rheumatoid Arthritis

Interventions

ABX464 50mgDRUG

ABX464 is a new anti-inflammatory drug

Matching PlaceboDRUG

placebo matching with ABX464

ABX464 100mgDRUG

ABX464 is a new anti-inflammatory drug

Methotrexate

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (24)

Cliniques Universitaires Saint-Luc

Brussels, Belgium

UZ Gent

Ghent, Belgium

Outcomes

Primary Outcomes

Number of Treatment-emergent Adverse Events in the ABX464 Treated Patients Versus Placebo

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

Time frame: through study completion, an average of 15 weeks

Secondary Outcomes

Number of Patients Achieving ACR20 Response

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.

Time frame: at Week 12

Number of Patients Achieving ACR20/50/70 Response

Number of patients who achieved at least 20%, 50% or 70% improvement in the American College of Rheumatology (ACR) response.

Time frame: Week 12

Change From Baseline in C-reactive Protein (CRP)

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

Time frame: Week 12

Number of Patients Achieving DAS28-CRP Response

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

Time frame: Week 12

Change From Baseline in Disease Activity Scores (DAS-CRP) (28 Joints) [DAS28]

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.

Data from ClinicalTrials.gov

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

UZ Leuven

Leuven, Belgium

ZNA Jan Palfijn

Merksem, Belgium

Fakultni Tomayerova nemocnice

Prague, Czechia

Revmatologicky ustav

Prague, Czechia

CHU de Brest - Hôpital Cavale Blanche

Brest, France

CHD Vendée

La Roche-sur-Yon, France

CHU de Montpellier - Lapeyronie

Montpellier, France

GHR Mulhouse Sud-Alsace

Mulhouse, France

...and 14 more locations

Change From Baseline in Erythrocyte Sedimentation Rate (ESR)

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

Time frame: Week 12

Number of Patients Achieving Disease Activity Score (DAS) DAS28-Erythrocyte Sedimentation Rate (ESR) [DAS28-ESR] Remission

Number of patients achieving Disease Activity Score (DAS) DAS28-Erythrocyte Sedimentation Rate (ESR) \[DAS28-ESR\]remission, which is defined as DAS2-ESR \< 2.6

Time frame: Week 12

Change From Baseline in Disease Activtiy Score (DAS)28-Erythrocyte Sedimentation Rate (ESR)

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

Time frame: 12 weeks

Change From Baseline in Simplified Disease Activity Index Score (SDAI)

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

Time frame: Week 12

Change From Baseline in Clinical Disease Activity Index Score (CDAI)

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

Time frame: Week 12

Number of Patients Achieving Low Disease Activity (LDA)

Number of patients achieving a Low Disease Activity (LDA) which is defined as DAS28-ESR \<=3.2

Time frame: Week 12

Number of Patients Achieving Simplified Disease Activity Score (SDAI) Remission

Number of patients achieving Simplified Disease Activity Score (SDAI) remission, which is considered achieved if the SDAI score ≤ 3.3

Time frame: Week 12

Number of Patients Achieving Clinical Disease Activity (CDAI) Remission

Number of patients achieving Clinical Disease Activity (CDAI) remission, which is considered achieved if the CDAI score ≤ 2.8

Time frame: Week 12

Number of Patients Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission

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

Time frame: Week 12

Change From Baseline in Tender/Painful Joint Count (TJC28)

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

Time frame: 12 weeks

Change From Baseline in Swollen Joint Count (SJC)

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

Time frame: 12 weeks

Change From Baseline in Pain Visual Analog Scale

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

Time frame: 12 weeks

Change From Baseline in Patient Global Assessment of Disease (PtGA)

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

Time frame: 12 weeks

Change From Baseline in Investigator Global Assessment of Disease (PrGA)

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

Time frame: 12 weeks

Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)

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

Time frame: 12 weeks