Clinical Trials Register

Summary
EudraCT Number:	2018-004677-27
Sponsor's Protocol Code Number:	ABX464-301
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-07-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2018-004677-27

A.3

Full title of the trial

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.

Randomizovaná, dvojitě zaslepená, placebem kontrolovaná klinická studie fáze IIa, s paralelními skupinami hodnotící různé dávky přípravku ABX464 v kombinaci s methotrexátem (MTX), u pacientů se středně těžkou až těžkou aktivní revmatoidní artritidou, u nichž nedošlo k žádoucí odpovědi na MTX a/anebo na léčbu blokátorem tumor nekrotizujícího faktoru alfa (TNFα), nebo při nesnášenlivosti léčby blokátorem TNFα.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Phase IIa study of ABX464 in moderate to severe active Rheumatoid Arthritis patients.

A.4.1

Sponsor's protocol code number

ABX464-301

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Abivax
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Abivax
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Abivax
B.5.2	Functional name of contact point	VP Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	5 Rue de la Baume
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75008
B.5.3.4	Country	France
B.5.4	Telephone number	+33 0 15383 0961
B.5.6	E-mail	paul.gineste@abivax.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	ABX464
D.3.2	Product code	ABX464
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABX464
D.3.9.2	Current sponsor code	ABX464
D.3.9.3	Other descriptive name	ABX464
D.3.9.4	EV Substance Code	SUB184487
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Rheumatoid Arthritis

E.1.1.1

Medical condition in easily understood language

Rheumatoid Arthritis (RA) is a chronic progressive inflammatory disease in the joints that often results in painful deformity and immobility, especially in the fingers, wrists, feet, and ankles.

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10003268
E.1.2	Term	Arthritis rheumatoid
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to evaluate the safety of ABX464 given at two different doses (100mg and 50 mg) vs placebo in combination with MTX when administered once daily in patients with moderate to severe active Rheumatoid Arthritis.

E.2.2

Secondary objectives of the trial

To evaluate the effects of the different dose groups of ABX464 at Weeks 2, 4, 8 and 12 on the American College of Rheumatology (ACR) 20/50/70 response and each of its components versus placebo;
To evaluate the effects of the different dose groups of ABX464 at Weeks 2, 4, 8 and 12 on disease activity scores (DAS28 scores, simplified disease activity score [SDAI] and clinical disease activity score [CDAI]) versus placebo;
To evaluate the effects of the different dose groups of ABX464 at Weeks 2, 4, 8 and 12 on clinical response (DAS28 EULAR good and moderate responses), Low Disease Activity (LDA) or remission (DAS28-ESR remission, ACR/EULAR remission, SDAI and CDAI remission) versus placebo;
To evaluate the effects of the different dose groups of ABX464 at Weeks 2, 4, 8 and 12 on the (PRO) & (HAQ-DI);
To assess the PK of the ABX464 and its main active metabolite N-Glu-ABX464 after oral administration of different daily doses of ABX464 in patients with rheumatoid Arthritis.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:
- Men or women age 18 - 75 years;
- Patient with a confirmed and documented diagnosis of adult-onset rheumatoid arthritis, for at least 12 weeks, according to the revised 2010 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 of ≥ 4 (28-joint count) and tender joint count ≥4 (28-joint count) at screening;
- Patient with a moderate to severe disease activity score DAS28 CRP of ≥ 3.2 and 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-TNFα therapy (both administered for at least 12 weeks before IR) or were intolerant to anti- TNFα therapy.
In addition, MTX treatment should be given at a stable dose ≥ 10 mg/week (for at least 4 weeks prior to randomization) and associated with folic acid ≥ 10 mg/week.
For the anti-TNFα therapy, the following wash-out period will be required:
o 30 days prior to randomization for adalimumab and etanercept
o 2 months prior to randomization for infliximab, certolizumab pegol, golimumab
- Patients with the following hematological and biochemical laboratory parameters obtained within 14 days prior to baseline:
o Hemoglobin > 9.0 g dL-1;
o Absolute neutrophil count ≥ 1000 mm-3;
o Platelets ≥ 100,000 mm-3;
o Total serum creatinine ≤ 1.3 x ULN (upper limit of normal);
o Creatinine clearance > 50 mL min-1 by the Cockcroft-Gault equation within 60 days prior to baseline;
o Total serum bilirubin < 1.5 x ULN;
o Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 1.5 x ULN;
o Negative screening for TB (or if positive, the use of anti-TB prophylaxis according to recommendation) and HIV, HCV, HBV
- Patients are able and willing to comply with study visits and procedures as per protocol;
- Patients should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures are performed;
- Patients should be affiliated to a social security regimen (for French sites only);
- Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination. Contraception should be in place at least 2 weeks prior to screening. Women must be surgically sterile or if of childbearing potential must use a highly effective contraceptive method. Women of childbearing potential (WOCBP) will enter the study after confirmed menstrual period and a negative pregnancy test. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) or hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing system, bilateral tubal ligation, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the patient. In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is required. This recommendation also applies to WOCBP with infrequent or irregular menstrual cycle. Female and male patients must not be planning pregnancy and male patients should use condom and must not donate sperm must not donate sperm during the trial and for 3 months post completion of their participation in the trial.

E.4

Principal exclusion criteria

The following criteria should be checked at the time of screening. If ANY exclusion criterion applies, the patient will not be included in the study:
- 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 CMV, herpes and/or recent infectious hospitalization;
- Acute, chronic or history of clinically relevant (as per investigator’s judgement) pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable 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 (approved or investigational) non-anti-TNF biological disease-modifying antirheumatic drugs (bDMARDs), and targeted DMARDs (tDMARDS) prior to baseline. These treatments include: IL-6 antagonists, Janus Kinase (JAK) inhibitors, cytotoxic T lymphocyte-associated molecule CTLA-4Fc Chimera, rituximab;
- Patient treated with systemic corticosteroids >10 mg/day during the 2 weeks prior to and at randomization; IV or IM injections of glucocorticoids 4 weeks prior to randomization and IA glucocorticoids 2 weeks prior to randomization;
- Patients treated with other immunosuppressive drugs;
- History of malignancy (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence) unless it has been treated and a cure is achieved for at least 5 years;
- Serious illness requiring systemic treatment and/or hospitalization within 3 weeks prior to baseline;
- Pregnant or breast-feeding woman;
- Illicit drug or alcohol abuse or dependency;
- Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer
- Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the incidence of treatment-emergent adverse events in the ABX464 treated Patients versus placebo, categorized by severity.

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoint of evaluation of this end point from day 0 to EoS.

E.5.2

Secondary end point(s)

Secondary Endpoints:
Main Efficacy Endpoint:
Proportion of patients achieving a categorical ACR20 response at Week 12.
The components of ACR20 assessment include:
o C-Reactive Protein (CRP) (mg/L),
o Tender/painful joint count (TJC) (28 joints),
o Swollen joint count (SJC) (28 joints),
o Patient assessment of joint pain (Pain-VAS),
o Patient global assessment of disease (PtGA),
o Physician's Global Assessment of Disease (PrGA),
o Disability index of the healthy assessment questionnaire (HAQ-DI)

Other secondary endpoints:
Change from Baseline in the following disease parameters at Week 2, Week 4, Week 8 and Week 12:
o Individual components of the ACR20 response (CRP, TJC(28), SJC(28), Pain-VAS, PtGA, PrGA, HAQ-DI);
o Erythrocyte Sedimentation Rate (ESR);
o DAS28-CRP and DAS28-ESR. The components of DAS28 assessment include TJC(28), SJC(28), CRP/ESR, and PtGA;
o SDAI score which includes TJC(28), SJC(28), CRP, PtGA, and PrGA;
o CDAI score which includes TJC(28), SJC(28), PtGA, and PrGA;
o FACIT-Fatigue score.

• Proportion of patients achieving at Week 2, Week 4, Week 8 and Week 12:
o ACR20/50/70 response
o Categorical DAS28-CRP response. Proportion of patients achieving categorical DAS28-CRP response will be measured as moderate/good European League Against Rheumatism (EULAR) response at each assessment time point;
o Low Disease Activity (LDA) (DAS28 ≤ 3.2)
o DAS28-ESR remission (DAS28 < 2.6)
o ACR/EULAR remission (TJC(28), SJC(28), CRP, and PtGA: all≤1);
o SDAI remission (SDAI ≤ 3.3);
o CDAI remission (CDAI ≤ 2.8).

PK parameters:
o Pre-dose plasma concentration of ABX464/N-Glu at Week 2 and Week 8;
o Post-dose plasma concentration of ABX464/N-Glu at 1-, 2- and 3-hours post-dose at Baseline, Week 2 and Week 8;
o Trough plasma concentration of ABX464/N-Glu at End of Study Visit

The number of incidences of treatment-emergent serious adverse events (through the whole study)
The number of incidences of treatment-emergent adverse events of special interest (through the whole study)
The number of incidences of adverse events leading to investigational product discontinuation (through the whole study)
The number of incidences of clinically significant laboratory abnormalities through the whole study)
The number of incidences of all AE (causally related and non-related) and SAE, further categorized by severity (through the whole study)

E.5.2.1

Timepoint(s) of evaluation of this end point

See E.5.2 for Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After Day 84, patients willing to carry on the study treatment will be able to take part in the long-term maintenance study (ABX464-302).
In any other case, patients will exit the study (EOS) and will be treated according to the standard of care. The ABX464-302 follow-up study is a separate clinical protocol subject to health authorities and ethics committee approvals.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-07-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-04-27

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