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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03813199
• Other study ID #: ABX464-301
• Status: Completed
• Phase: Phase 2
• Start date: July 4, 2019
• Est. completion date: April 27, 2021

Study information

• Verified date: May 2022
• Source: Abivax S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 27, 2021
• Est. primary completion date: April 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 (TNFa) therapy (both administered for at least 12 weeks before IR) or were intolerant to anti- TNFa 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	ZNA Jan Palfijn	Merksem
Czechia	Fakultni Tomayerova nemocnice	Praha
Czechia	Revmatologicky ustav	Praha
France	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	CHU de Nice - Hôpital Pasteur	Nice
France	CHR d'Orléans	Orléans
France	APHP - Hôpital Salpétrière	Paris
France	CHU de Tours - Hôpital Trousseau	Tours
Hungary	Complex Medical Centre - Déli Klinika	Budapest
Hungary	CRU Hungary Ltd.	Miskolc
Hungary	CMed Rehabilitációs és Diagnosztikai Központ	Székesfehérvár
Poland	ClinicMed Daniluk, Nowak Sp. J.	Bialystok
Poland	Pratia MCM	Kraków
Poland	Zespól Poradni Specjalistycznych REUMED	Lublin
Poland	NZOZ Lecznica MAK-MED S.C.	Nadarzyn
Poland	Medyczne Centrum Hetmanska	Poznan
Poland	National Institute of Geriatrics	Warszawa
Poland	RHEUMA MEDICUS Zaklad Opieki Zdrowotnej	Warszawa

Sponsors (1)

Lead Sponsor	Collaborator
Abivax S.A.

Countries where clinical trial is conducted

Belgium,  Czechia,  France,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	through study completion, an average of 15 weeks
Secondary	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.	at Week 12
Secondary	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.	Week 12
Secondary	Change From Baseline in C-reactive Protein (CRP)	Change from baseline in C-reactive protein (CRP) at Week 12	Week 12
Secondary	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	Week 12
Secondary	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 v (TJC28) + 0.28 v (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.	Week 12
Secondary	Change From Baseline in Erythrocyte Sedimentation Rate (ESR)	Change from baseline in erythrocyte sedimentation rate (ESR) at Week 12	Week 12
Secondary	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	Week 12
Secondary	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 v (TJC28) + 0.28 v (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	12 weeks
Secondary	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	Week 12
Secondary	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	Week 12
Secondary	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	Week 12
Secondary	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	Week 12
Secondary	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	Week 12
Secondary	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	Week 12
Secondary	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	12 weeks
Secondary	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	12 weeks
Secondary	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	12 weeks
Secondary	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	12 weeks
Secondary	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	12 weeks
Secondary	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	12 weeks