Clinical Trials Register

Summary
EudraCT Number:	2022-002724-12
Sponsor's Protocol Code Number:	E22-04
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2023-02-14
Trial 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Bulgarian Drug Agency

A.2

EudraCT number

2022-002724-12

A.3

Full title of the trial

A phase IIb randomized, placebo-controlled, double-blind study, to evaluate the efficacy and safety of FBR-002 in participants hospitalized with COVID-19 in need of supplemental oxygen and at risk of severe outcome

Фаза 2б рандомизирано, плацебо-контролирано, двойно-сляпо изпитване за оценка на ефикасността и безопасността на FBR-002 при хоспитализирани пациенти с COVID-19, при които има нужда от допълнителен кислород и риск от влошаване на състоянието и смърт

A.3.1

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

Evaluation of the efficacy and safety of a polyclonal equine fragments immunotherapy (FBR-002) in participants with COVID-19 requiring supplemental oxygen in hospital and at risk of severe outcome

Оценка на ефикасността и безопасността на имунотерапия от поликлонални фрагменти от конски произход (FBR-002) при участници с COVID-19, при които има нужда от допълнителен кислород и риск от влошаване на състоянието и смърт

A.4.1

Sponsor's protocol code number

E22-04

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	Fab'entech
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	European Commission (Hera Incubator - EPIC Crown-2 project)
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fab'entech
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	24 rue Jean Baldassini
B.5.3.2	Town/ city	Lyon
B.5.3.3	Post code	69007
B.5.3.4	Country	France
B.5.4	Telephone number	+33666211429
B.5.6	E-mail	sabine.kacel@fabentech.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	FBR-002
D.3.2	Product code	FBR-002
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Anti-SARS-CoV-2 F(ab')2 fragments
D.3.9.3	Other descriptive name	Anti-SARS-CoV-2 polyclonal immunoglobulin F(ab')2 fragments
D.3.9.4	EV Substance Code	SUB218519
D.3.10	Strength
D.3.10.1	Concentration unit	ELISA unit/ml enzyme-linked immunosorbent assay unit/millitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25.9
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COVID-19 in hospitalized patients in need of supplemental oxygen and at risk of severe outcome

E.1.1.1

Medical condition in easily understood language

COVID-19

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	PT
E.1.2	Classification code	10084268
E.1.2	Term	COVID-19
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the effect of FBR-002 compared to placebo on the WHO-CPS in participants hospitalized with COVID-19 in need of supplemental oxygen at Day 28 after randomization

E.2.2

Secondary objectives of the trial

To determine the effect of FBR-002 compared to placebo on: the WHO-CPS in participants hospitalized with COVID-19 in need of supplemental oxygen between Day 0 and Day 14
To determine the effect of FBR-002 on:
•The need for SoC intensification up to Day 14
•The disease progression within 28 days after randomization.
•The overall survival at 28, 60 and 90 days after randomization.
•The mortality rate related to respiratory failure due to COVID-19 within 90 days after randomization.
•The WHO-CPS at Day 60 after randomization.
•The time to hospital discharge within 60 days post-randomization.
•The frailty of participants
•Viral variants and viral load reduction.
•The incidence and time to being free of any respiratory support.
•SpO2/FiO2-ratio at days 3, 5 and 8 after randomization.
•The occurrence of clinical and laboratory adverse events, including serious adverse events especially those leading to discontinuation of study treatment or to death.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

I1. Male or female ≥18 years old and ≤ 90 years old
•≥70 years old with or without any risk factor
•Or <70 years old and the presence of at least one of the following risk factors from the medical history:
oTreated arterial hypertension (all stages);
oObesity (Body Mass Index [BMI] ≥ 30kg/m²) or severe obesity (BMI ≥ 40 kg/m²);
oAll types of diabetes (type 1 and type 2);
oAny history of heart conditions disease (such as heart failure, coronary artery disease, cardiomyopathies or hypertension);
oStroke or cerebrovascular disease history;
oChronic lung diseases, including but not limited to COPD (chronic obstructive pulmonary disease), asthma (moderate to severe), interstitial
lung disease, cystic fibrosis and pulmonary hypertension;
oMalignancies: solid tumor that are progressive or treated within the year prior to participant screening/or blood malignancies that are
progressive or treated within the 3 years prior to participant screening in the study;
oImmunocompromised state (this includes participants who are suffering from primary immunodeficiencies; participants under treatment with
corticosteroids either oral or parenteral (at least 10 mg per day prednisone-equivalent for at least 14 days prior to randomization);
participants receiving active chemotherapy; participants on biological treatment or treatment with JAK inhibitors);
oSolid organ or blood stem cell transplant;
oDown syndrome;
oKnown HIV infection;
oLiver failure of stage 1 and 2 based on the Child-Pugh classification;
oRenal failure (grade 1, 2, 3a and 3b according to KDIGO classification);
oHemoglobin blood disorders (like Thalassemia, Sickle Cell Disease…);
oDementia or other neurological conditions;
oAbsence of anti-SARS-CoV2 IgM or IgG at screening;
I2. Participant must be able to understand and comply with the conditions of the protocol and must have read and understood the consent form and provide written informed consent (provided by the participant or by a legal representative);
I3. Biologically confirmed SARS-CoV-2 infection ≤ 10 days before screening (either by PCR or antigenic test);
I4. First onset of COVID-19 symptoms ≤ 10 days, like fever and/or chills, headache, myalgia, cough, shortness of breath, fatigue, new loss of taste or smell;
I5. Findings in chest-X-ray or in chest computed tomography compatible with lower respiratory tract infection (precision for imaging: typical imaging features related to COVID-19);
I6. Participant admitted to hospital for COVID-19, but outside of the Intensive Care Unit;
I7. Participant requiring low-flow O2 supplement ≤ 6L/min by mask or nasal prongs at screening;
I8. Score of 5 on the WHO 11-point Clinical Progression Scale at screening;
I9. Female of childbearing potential must have a serum negative pregnancy test at screening. Male and female of childbearing potential must use a highly effective method of contraception during treatment and at least for 1 month after the last dose of study treatment;
I10. Participant must not be receiving therapy in a concurrent clinical trial at the time of screening and also 30 days prior to the screening and must agree not to participate in any other interventional clinical studies during their participation in this trial.

E.4

Principal exclusion criteria

E1. Score <5 or ≥6 on the WHO 11-point Clinical Progression Scale at screening;
E2. Respiratory rate >30 breaths/min in adults under adequate oxygen;
E3. Liver failure > stage 3 according to the Child-Pugh classification;
E4. Severe renal failure (≥ grade 4 according to KDIGO classification);
E5. Any anti-SARS-CoV-2 vaccine injection performed less than 21 days prior to screening;
E6. Known allergy or hypersensitivity or intolerance to study product components;
E7. History of anaphylaxis during or prior administration of equine serum (i.e anti-tetanus serum or anti-ophidic serum or anti-arachnid toxic serum or anti-rabies serum) or allergic reaction due to contact or exposure to horses;
E8. Participants with short life expectancy or with any severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect the participant’s participation to the study;
E9. Septic shock ongoing at the time of screening or within the last 30 days of screening.

E.5 End points

E.5.1

Primary end point(s)

To determine the effect of FBR-002 compared to placebo on the distribution of frequencies of the WHO-CPS from 1 to 10 at Day 28 after randomization

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 28

E.5.2

Secondary end point(s)

Key secondary endpoints:
To determine the effect of FBR-002 compared to placebo on:
•[2.1.1] Mean area under the curve (AUC) of WHO-CPS Day 0 to Day 14
•[2.1.2] The distribution of frequencies of the WHO-CPS (from 1 to 10) at Day 14 after randomization

Other secondary endpoints:
To determine the effect of FBR-002 on:
•[2.2] Proportion of participants that needed a SoC intensification up to Day 14
•[2.3.1] Time from Day 0 to occurrence of disease progression within 28 days from randomization
•[2.3.2] Percentage of participants who have progressed their WHO-CPS to more or equal to 6 within 7, 14 and 28 days after randomization
•[2.4] Overall survival at 28, 60 and 90 days from randomization.
•[2.5] Mortality rate related to respiratory failure due to COVID-19 up to 90 days from randomization.
•[2.6] The distribution of frequencies of the WHO-CPS (from 1 to 10) at Day 60 after randomization
•[2.7] Time from Day 0 to hospital discharge within 60 days post-randomization.
•[2.8] Evolution of mean clinical frailty score from Day 0 to day 28
•[2.9.1] Variant identification determined at Day 1 and Day 14, or early discontinuation visit (EDV).
•[2.9.2] Mean viral load as assessed by SARS-CoV-2 RT-qPCR during hospitalization.
•[2.9.3] Association between FBR-002 treatment and the proportion of participants with a variant at Day 14 (or EDV) different from the one at Day 1
•[2.9.4] Association between viral load and baseline viral variant.
•[2.10.1] Cumulative incidence of being free of any respiratory support
•[2.10.2] Time to being free of any respiratory support.
•[2.11] Mean changes from randomization of SpO2/FiO2-ratio at days 3, 5 and 8 after randomization.
•[2.12] Occurrence of clinically significant laboratory abnormalities, and adverse events, including serious adverse events (SAEs) especially those leading to discontinuation of study treatment or to death.

E.5.2.1

Timepoint(s) of evaluation of this end point

•[2.1.1] Day 0 to Day 14
•[2.1.2] at Day 14
•[2.2]Day 0 to Day 14
•[2.3.1] Day 0 to Day 28
•[2.3.2] Day 0 to Day 7, Day 14 and Day 28
•[2.4] Day 28, Day 60 and Day 90
•[2.5] Day 0 to Day 90
•[2.6] Day 60
•[2.7] Day 0 to Day 60
•[2.8] Day 0 to Day 28
•[2.9.1] Day 1 and Day 14, or early discontinuation visit (EDV).
•[2.9.2] Day 1, Day 4, Day 7 and Day 14, or early discontinuation visit (EDV).
•[2.9.3] Day 1 and Day 14
•[2.9.4] Day 1, Day 4, Day 7 and Day 14, or early discontinuation visit (EDV).
•[2.10.1] Day 0 to discharge
•[2.10.2] Day 0 to discharge
•[2.11] Day 3, Day 5 and Day 8
•[2.12] Day 0 to Day 90

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

Yes

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)

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 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:

142

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

143

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

285

F.4.2.2

In the whole clinical trial

285

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)

There will be no further study related intervention after the end of the study. Plans for treatment or care after the subject has ended the participation in the trial will be the expected normal treatment of that condition.

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

2023-03-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-05-12

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials