Clinical Trials Register

Summary
EudraCT Number:	2020-001673-75
Sponsor's Protocol Code Number:	ABX464-401
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-07-01
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2020-001673-75

A.3

Full title of the trial

A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the
efficacy and the safety of ABX464 in treating inflammation and preventing COVID-19
associated acute respiratory failure in patients aged ≥ 65 and patients aged ≥18 with
at least one additional risk factor who are infected with SARS-CoV-2. (the MiR-AGE
study).

A.3.1

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

Phase 2/3 study of ABX464, once daily oral capsule, in high risk patients infected by SARS-CoV-2 prior to respiratory distress.

A.4.1

Sponsor's protocol code number

ABX464-401

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	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.5.6	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.3.2	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.3.9.2	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

Infection with SARS-CoV-2 virus, COVID-19 infection

E.1.1.1

Medical condition in easily understood language

The coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by a novel coronavirus, that has been exported around the globe to reach pandemic proportion.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

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 determine the efficacy of ABX464 50mg to prevent respiratory failure or death in study patients.

E.2.2

Secondary objectives of the trial

Evaluate the proportion of patients requiring hospitalization compared to the {Standard of care + placebo} group
Assess the proportion of patients reporting each severity rating on a 7-point ordinal scale
Assess the time to an improvement of one category of the a 7-point on an ordinal scale from baseline
Evaluate and compare the effect of ABX464 on immunophenotyping and cytokines levels
Evaluate the proportion of patient requiring oxygen supplementation
Assess the time to hospitalization
Evaluate the time to application of invasive and non-invasive mechanical ventilation or high flow oxygen therapy
Assess the IMV and/or NIV duration
Assess the oxygen supplementation (>3L/min) duration
Assess the hospital stay duration
Evaluate the effect of ABX464 on miR-124 expression
Assess the change in CRP, Troponin I & T and D-dimer levels
Evaluate the prevention of Covid-19 related deaths
Evaluate SARS-CoV-2 infection in subjects
Evaluate the safety

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A patient will be eligible to participate in this study if ALL the following criteria are met:
1. Adult (≥ 18 years old) men or women hospitalizedor not hospitalized, diagnosed
for SARS-CoV-2 infection by PCR (within 48 hours prior to randomization) with at least one associated risk factor. Considered risk factors are:
• Age ≥ 65 years
• Obesity defined as BMI ≥ 30
• Recent histroy of uncontrolled High Blood Pressure (SBP > 150 mm Hg & DBP >100 mm Hg) according to investigator
• Treated diabetes (type I or II)
• History of ischemic cardiovascular disease
2. Symptomatic patients must present at least 1 of the following symptoms at enrollment: fever or perceived fever (for more than 24 hours), headache, sore throat, dry cough, fatigue, chest pain or choking sensation (with no associated respiratory distress), myalgia, anosmia, ageusia or gastro-intestinal symptoms.
3. Patients with pulse oximetry arterial saturation (SpO2) ≥ 92 % on room air at
enrolment.
4. Patients with the following hematological and biochemical laboratory parameters obtained within 7 days prior to D0:
• Hemoglobin > 9.0 g dL-1
• Absolute Neutrophil Count ≥ 1000 mm-3;
• Platelets ≥ 100,000 mm-3;
• Creatinine clearance ≥ 50 mL min-1 by the Cockcroft-Gault formula
• Total serum bilirubin < 2 x ULN
• Alkaline phosphatase< 2 x ULN, AST (SGOT) and ALT (SGPT) < 3 x ULN;
5. Women of child bearing potential and men receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 6 months (180 days) after end of study or early termination. Contraception should be in place at least 2 weeks prior to enrolment. 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 during the trial and for 6 months post completion of their participation in the trial. In addition, male patients should use condom during the trial and for 6 months (180 days) post completion of their participation in the study. Male patients must not donate sperm as long as contraception is required. For the purpose of this protocol, a woman is
considered of childbearing potential (WOCBP), i.e. fertile, following menarche
and until becoming post-menopausal unless permanently sterile. Permanent
sterilisation methods include hysterectomy, bilateral salpingectomy and
bilateral oophorectomy. A postmenopausal state is defined as no menses for
12 months without an alternative medical cause. A high follicle stimulating
hormone (FSH) level in the postmenopausal range may be used to confirm a
post-menopausal state in women not using hormonal contraception or
hormonal replacement therapy. However, in the absence of 12 months of
amenorrhea, a single FSH measurement is insufficient. Finally a man is
considered fertile after puberty unless permanently sterile by bilateral
orchidectomy.
6. Patients must understand, sign and date the written voluntary informed consent form at the visit prior to any protocol-specific procedures.
7. Patients able and willing to comply with study visits and procedures as per protocol.
8. Patients should be affiliated to a social security regimen (for French sites only).

E.4

Principal exclusion criteria

Patients who meet any of the following exclusion criteria will be excluded from the study:
1. Patients with moderate or severe acute respiratory failure or requiring non-invasive ventilation or oxygen or with SpO2 < 92% or tachypnea (respiratory rate ≥ 30 breaths/min).
2. Patients treated with immunosuppressors and/or immunomodulators (cf.
Appendix #2).
3. Engrafted patients (organ and/or hematopoietic stem cells).
4. Patients with uncontrolled auto-immune disease.
5. Patients with known or suspected active (i.e. not controlled) bacterial, viral
(excluding COVID-19) or fungal infections.
6. Patients with preexisting, severe and not controlled organ failure.
7. History or active malignancy requiring chemotherapy or radiation therapy (excluding 2 years disease free survivor patients).
8. Pregnant or breast-feeding women.
9. Illicit drug or alcohol abuse or dependence that may compromise the patient's safety or adherence to the study protocol.
10. Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer.
11. Hypersensitivity to ABX464 and/or its excipients.
12. 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)

Rate of patients with no invasive or non-invasive mechanical ventilation (IMV and NIV, respectively), but excluding simple nasal/mask oxygen supplementation, and who are alive at the end of the 28 days period.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 28

E.5.2

Secondary end point(s)

1.Rate of patients hospitalized in both treatment groups
2. Percentage of patients reporting each severity rating on a 7-point ordinal scale at each study visit (i.e. Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death);
3.Mean change in the ranking on an ordinal scale from baseline to days 7, 14, 21, 28, 48 and at 4 months.
4.Change from enrolment in inflammatory markers in plasma (i.e. MCP-1, MIP-1 α, G-CSF, IL-1b, IL-2, IL-6, IL-7, IL-10, IL-17, INFg and TNFa) and in immune phenotype and assessment of cell-activation markers in PBMCs at D14, D28.
5.Rate of patients requiring oxygen supplementation in both treatment groups.
6.Time to hospitalization (log rank) from baseline in both treatment groups.
7.Time to assisted ventilation and oxygen supplementation (log rank) from baseline in both treatment groups.
8.Number of days of assisted ventilation in both treatment groups.
9.Number of days of oxygen supplementation in both treatment groups.
10.Number of days at the hospital from admission to discharge in both treatment groups.
11.Change from baseline in microRNA-124 levels in total blood (PAXgene®) at D0, D7 and D28 in both treatment groups.
12.AUC and % of change from enrolment in CRP, Troponin I & T and D-dimer levels in both treatment groups.
13.Time to death (log rank) and mortality rate (all causes, and Covid-19 related) in both treatment groups.
14.SARS-CoV-2 virus in nasopharyngeal sample and/or in blood at Day 0, 7, 14, 21, and 28.
15.Number and rates of participants with Treatment Emergent Adverse Event
16.Cumulative incidence of serious adverse events (SAEs) - including adverse drug reactions (SARs) and suspected unexpected serious adverse reactions (SUSARs)
17.Cumulative incidence of Grade 3 and 4 adverse events (AEs)
18.Number of participants with a discontinuation or temporary suspension of study drugs (for any reason)
19.Central blinded review of the hospitalization discharge CT-Scans for descriptive analysis with regards to the disease severity and outcomes.
20. Change from last dosing day in the Medical Research Council (MRC) dyspnea scale in the hospitalized patient’s population according to treatment group.
21. Optional: Change from last dosing day in Pulmonary Function Tests (PFT) (Forced Expiratory Volume (FEV) and slow and forced Vital Capacity (VC)) and Carbon Monoxide Diffusing Capacity (CMDC) tests in the hospitalized patients population according to treatment group.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. During the course of the study
2. During the course of the study
3. Days 7, 14, 21, 28, 48 and at 4 months from baseline
4. Days 14 and 28
5. During the course of the study
6. During the course of the study
7. During the course of the study
8. During the course of the study
9. During the course of the study
10. During the course of the study
11. Days 0, 7 and 28
12. During the course of the study
13. During the course of the study
14. Days 0, 7, 14, 21 and 28
15. During the course of the study
16. During the course of the study
17. During the course of the study
18. During the course of the study
19. During the course of the study
20. During the course of the study
21. During the course of the study

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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)

Yes

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

Chile

Mexico

Peru

Belgium

France

Germany

Italy

Spain

United Kingdom

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

The study will end once all the recruited patients have performed their safety follow-up and the End of Study visit, and all the data have been analyzed and computed in the clinical study report (CSR).

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 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:

344

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

690

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

400

F.4.2.2

In the whole clinical trial

1034

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)

Standard of care

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

2020-08-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-10

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-04-16

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