Clinical Trials Register

Summary
EudraCT Number:	2020-001782-37
Sponsor's Protocol Code Number:	PО-COV-III-20
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-06-15
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2020-001782-37

A.3

Full title of the trial

A multi-centre, adaptive, randomized, double-blind, placebo-controlled comparative clinical trial of the safety and efficacy of 12 mg Polyoxidonium®, lyophilizate solution for injections (NPO Petrovax Pharm LLC, Russia), in patients with coronavirus disease (COVID-19)

Multicentrické, adaptívne, randomizované, dvojito zaslepené, placebom kontrolované porovnávacie klinické skúšanie bezpečnosti a účinnosti 12 mg Polyoxidonium®, lyofilizát na injekčný roztok (NPO Petrovax Pharm LLC, Rusko), u pacientov s koronavírusovým ochorením (COVID-19)

A.3.1

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

A multi-centre, adaptive, randomized, double-blind, placebo-controlled comparative clinical study of the safety and efficacy of 12 mg Polyoxidonium®, lyophilizate solution for injections (NPO Petrovax Pharm LLC, Russia) in patients with coronavirus disease (COVID-19).

A.4.1

Sponsor's protocol code number

PО-COV-III-20

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	NPO Petrovax Pharm, LLC
B.1.3.4	Country	Russian Federation
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	NPO Petrovax Pharm, LLC
B.4.2	Country	Russian Federation
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NPO Petrovax Pharm, LLC
B.5.2	Functional name of contact point	PVX Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Presnenskaya еmbankment 12, floor 38
B.5.3.2	Town/ city	Moscow
B.5.3.3	Post code	123112
B.5.3.4	Country	Russian Federation
B.5.4	Telephone number	+7495730-75-45*125
B.5.5	Fax number	+7495730-75-60
B.5.6	E-mail	dodonovns@petrovax.ru

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	Yes
D.2.1.1.1	Trade name	Polyoxidonium
D.2.1.1.2	Name of the Marketing Authorisation holder	NPO Petrovax Pharm, LLC
D.2.1.2	Country which granted the Marketing Authorisation	Russian Federation
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.3.4	Pharmaceutical form	Lyophilisate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular and intravenous use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Azoximer bromide
D.3.9.1	CAS number	0892497-01-7
D.3.9.2	Current sponsor code	Polyoxidonium® (azoximer bromide)
D.3.9.3	Other descriptive name	AZOXIMER BROMIDE
D.3.9.4	EV Substance Code	SUB129591
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	6
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	Lyophilisate for solution for injection
D.8.4	Route of administration of the placebo	Intramuscular and intravenous use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

E.1.1.1

Medical condition in easily understood language

Hospitalized patients with coronavirus disease (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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10035737
E.1.2	Term	Pneumonia viral
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 assess safety and efficacy of Polyoxidonium®, lyophilizate solution for injections in dose of 12 mg (NPO Petrovax Pharm LLC, Russia) in comparison with placebo in hospitalized patients with coronavirus disease (COVID-19).

E.2.2

Secondary objectives of the trial

1. To evaluate clinical efficacy of Polyoxidonium®, lyophilizate solution for injections in dose of 12 mg (NPO Petrovax Pharm LLC, Russia) compared to placebo in hospitalized adult patients with COVID-19.
2. To evaluate safety of Polyoxidonium®, lyophilizate solution for injections in dose of 12 mg (NPO Petrovax Pharm LLC, Russia) compared to placebo in hospitalized adult patients with COVID-19.

Additional objective of part 1 of the study.
To define the primary efficacy endpoint for subsequent assessment of efficacy of Polyoxidonium®, lyophilizate solution for injections in dose of 12 mg (NPO Petrovax Pharm LLC, Russia) in patients with COVID-19.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Hospitalized (at the time of recruitment) male and female patients from 18 to 85 years of age.
2. The patient (or his/her legal representative, if the patient is not able to sign the form) signed an Informed Consent form for participation in this study before any initiation of any study procedures.
3. The patient (or his/her legal representative, if the patient is not able to sign the form) can understand all protocol requirements, perform the study procedures, and agree to all limitations specified in the protocol.
4. Confirmed diagnosis of coronavirus disease (COVID-19): laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 14 days prior to randomization.
5. Illness (coronavirus disease COVID-19) of any duration, and at least one of the following:
− Radiographic/tomographic chest infiltrates by imaging (chest x-ray, CT scan, etc.), OR
− Evidence of rales/crackles on clinical exam AND SpO2 ≤ 94% on room air, OR
− Indications for mechanical ventilation and/or supplemental oxygen.
6. Agrees to use adequate contraception methods (the methods with at least 90% efficacy include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), condom with intravaginal spermicide, cervical caps with spermicide, diaphragms with spermicide, bilateral tubal occlusion, vasectomised partner) or complete sexual abstinence for the study period and within 30 days after completion of the study (applicable for male patients and women of childbearing potential).

E.4

Principal exclusion criteria

1. History of clinically significant allergic reactions.
2. Hypersensitivity and/or intolerability to any ingredient of the investigational product or placebo.
3. Anticipated transfer to another hospital which is not a study centre within the next 72 hours.
4. Acute or chronic renal failure.
5. History of HIV infection, tuberculosis.
6. Conditions associated with primary immunodeficiency, established by assessing the history and by interviewing the patient..
7. Concomitant use of medications cytostatic drugs (including but not limited to alkylating agents, platinum analogues, dna intercalating agents, anticancer antibiotics, mitosisinhibitors, taxanes, topoisomerase inhibitors, antimetabolites) to treat a concomitant disease.
8. Systemic connective tissue diseases.
9. Need for the prohibited medications that are not part of the locally/internationally approved treatment of COVID-19.
10. Administration of convalescent plasma or intravenous immunoglobulin (IVIg) for coronavirus disease COVID-19 therapy ever.
11. Administration of any live vaccine within 4 weeks before screening or intending to receive a live vaccine during the study.
12. Administration of medications that are prohibited or unauthorized by the protocol within 2 weeks before the expected randomization date.
13. Administration or intending to receive an extracorporeal blood purification (EBP) device to remove pro-inflammatory cytokines from the blood, such as a cytokine filtering or absorption device (for example, CytoSorb ®).
14. History of alcohol or drug dependence.
15. History of malignant tumours of any location with remission for less than 2 years.
16. History of psychic (including depressive) disorders, physical and other factors that do not allow for adequate self-assessment of one’s behaviour and for compliance with the protocol requirements, including history of psychiatric disorders.
17. Pregnancy or breastfeeding.
18. IV injections and/or sampling of the required amount of blood is not possible.
19. Positive pregnancy test (in patients with childbearing potential).
20. Participation in any clinical study within 30 days before enrolment in this study.
21. History of any condition that the study doctor considers significant enough to prevent enrolment of this patient.

E.5 End points

E.5.1

Primary end point(s)

The initial primary efficacy outcome is clinical status of the patient at Day 15 based on a 7-point ordinal scale:
1. Not hospitalized, no limitations on activities
2. Not hospitalized, limitation on activities
3. Hospitalized, not requiring supplemental oxygen
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, on non-invasive ventilation or high flow oxygen devices
6. Hospitalized, on invasive mechanical ventilation or ECMO
7. Death.

E.5.1.1

Timepoint(s) of evaluation of this end point

The endpoint methodology is taken from the WHO Master Protocol, which recommends an initial primary end-point for the Phase IIb part of the study that is then updated after a blinded interim analysis (after 100 patients have been recruited) for the Phase III part of the study (1) .
According to WHO Master Protocol, it was planned that the primary endpoint (clinical status on the ordinal scale) would be evaluated on day 15 during the first part of the study. The day of the primary endpoint could be modified based on a blinded evaluation of the primary efficacy outcome on various days (days 7-21).

E.5.2

Secondary end point(s)

• Clinical status on the 7-point ordinal scale:
o Clinical status - Days 3, 5, 8, 11 and 29.
o Time to improvement in clinical status by one category from admission - Day 1 (baseline) then every day up to and including day 17.
o Change in clinical status from baseline - Days 1 (baseline), 3, 5, 8, 11, 15, and 29.

• Clinical status on the National Early Warning Score (NEWS):
o The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first - Every day up to and including day 17.
o Change in NEWS from baseline - Days 1 (baseline), 3, 5, 8, 11, 15, and 29

• Oxygenation:
o Oxygenation free days in the first 28 days (on Day 29).
o Incidence and duration of new oxygen use during the study (on Day 29).

• Mechanical Ventilation:
o Ventilator free days in the first 28 days (on Day 29).
o Incidence and duration of new mechanical ventilation use during the trial (on Day 29).

• Hospitalization:
o Duration of hospitalization (days) - on Day 29.

• Mortality:
o 28-day mortality - on Day 29.

E.5.2.1

Timepoint(s) of evaluation of this end point

• 7-point ordinal scale:
o Clinical status - Days 3, 5, 8, 11 and 29
o Time to improvement - Day 1 (baseline) then every day up to and including day 17
o Change in clinical status from baseline - Days 1, 3, 5, 8, 11, 15, and 29
• NEWS:
o The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first - Every day up to and including day 17
o Change in NEWS from baseline - Days 1, 3, 5, 8, 11, 15, and 29
• Oxygenation:
o Oxygenation free days in the first 28 days (Day 29)
o Incidence and duration of new oxygen use (on Day 29)
• Mechanical Ventilation:
o Ventilator free days in the first 28 days (Day 29)
o Incidence and duration of new mechanical ventilation use (on Day 29)
• Hospitalization - Day 29
• Mortality - Day 29

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

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

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

Russian Federation

France

Italy

Poland

Romania

Slovakia

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 end of the trial is the last visit of the last subject undergoing the trial.

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

E.8.9.2

In all countries concerned by the trial days

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:

227

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

227

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

464

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)

None

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

2020-11-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-03-05

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