Clinical Trials Register

Summary
EudraCT Number:	2020-003614-13
Sponsor's Protocol Code Number:	hzVSF_v13-0006
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-23
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-003614-13

A.3

Full title of the trial

Efficacy and safety of intravenously administered hzVSF-v13 in patients with COVID-19 pneumonia: a phase II, proof of concept, multicentre, randomized, parallel-group, double-blind, placebo-controlled study

Efficacia e sicurezza di hzVSF-v13 somministrato per via endovenosa in pazienti affetti da polmonite da COVID-19: studio proof of concept di fase II, multicentrico, randomizzato, a gruppi paralleli, in doppio cieco, controllato verso placebo

A.3.1

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

Study with hzVSF-v13 in patients with COVID-19 pneumonia: a phase II, proof of concept, multicentre, randomized, parallel-group, double-blind, placebo-controlled study

Studio con hzVSF-v13 somministrato per via endovenosa in pazienti affetti da polmonite da COVID-19: studio proof of concept di fase II, multicentrico, randomizzato, a gruppi paralleli, in doppio cieco, controllato verso placebo

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

hzVSF_v13-0006

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	ImmuneMed Inc.
B.1.3.4	Country	Korea, Republic of
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	ImmuneMed Inc.
B.4.2	Country	Korea, Republic of
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	OPIS s.r.l.
B.5.2	Functional name of contact point	Dipartimento Medico
B.5.3	Address:
B.5.3.1	Street Address	Palazzo Aliprandi - Via Matteotti, 10
B.5.3.2	Town/ city	Desio (MB)
B.5.3.3	Post code	20832
B.5.3.4	Country	Italy
B.5.4	Telephone number	03626331
B.5.5	Fax number	0362633633
B.5.6	E-mail	info.studiclinici@opis.it

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	hzVSF-v13
D.3.2	Product code	[hzVSF-v13]
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.3.9.2	Current sponsor code	hzVSF-v13
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	200
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
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

Moderate-to-severe COVID-19 pneumonia

Polmonite da COVID-19 da moderata a severa

E.1.1.1

Medical condition in easily understood language

Moderate-to-severe COVID-19 pneumonia

Polmonite da COVID-19 da moderata a severa

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10053983
E.1.2	Term	Corona virus infection
E.1.2	System Organ Class	100000004862

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 preliminarily investigate the safety and efficacy of two doses of hzVSF-v13 + SOC vs. placebo + SOC for the treatment of COVID-19 pneumonia.
- To characterize the pharmacodynamic effects of the hzVSF-v13 doses.

- Studiare in modo preliminare la sicurezza e l’efficacia di due dosi di hzVSF-v13 + SOC vs. placebo + SOC per il trattamento della polmonite da COVID-19.
- Caratterizzare gli effetti farmacodinamici delle dosi di hzVSF-v13.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed written informed consent from any patient capable of giving consent, or, when the patient is incapable of doing so, by his or her legal/authorized representative. Note: In accordance with the European Medicines Agency (EMA) “Guidance on the management of clinical trials during the covid-19 (coronavirus) pandemic version 3 28/04/2020”, if written consent by the trial participant is not possible (for example because of physical isolation due to COVID-19 infection), consent may be given orally by the trial participant in the presence of an impartial witness.
2. Age 18 years or older.
3. Patient is currently hospitalized.
4. Diagnosis of COVID-19 pneumonia including a positive RT-PCR test for SARS-CoV-2 of any specimen and lung involvement confirmed with chest imaging (X-ray or computed tomography [CT] scan).
5. Able to comply with the study protocol.
6. Female patients must be postmenopausal (24 months of amenorrhea), surgically sterile or must agree to use an effective method of contraception throughout the study and for up to 120 days after stopping treatment. Effective contraception includes an established hormonal therapy or intrauterine device for females, and the use of a barrier contraceptive (i.e. diaphragm or condoms) with spermicide.

1. Consenso informato scritto per qualsiasi paziente in grado di dare il consenso, oppure, nel caso in cui il paziente non sia in grado di farlo, consenso da parte del suo rappresentante legale/autorizzato. Nota: in conformità alla linea guida sulla gestione degli studi clinici durante la pandemia da coronavirus (“Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic version 3 28/04/2020”) dell’Agenzia Europea del Farmaco (European Medicines Agency – EMA), se non è possibile ottenere il consenso scritto da parte del partecipante allo studio (ad esempio a causa dell’isolamento fisico dovuto all’infezione da COVID-19), il consenso può essere dato verbalmente dal partecipante allo studio in presenza di un testimone imparziale.
2. Età uguale o superiore a 18 anni.
3. Paziente attualmente in regime di ricovero.
4. Diagnosi di polmonite da COVID-19 compreso un test RT-PCR positivo per SARS-CoV-2 su qualsiasi campione e coinvolgimento polmonare confermato tramite diagnostica per immagini del torace (radiografia o TAC).
5. Paziente in grado di aderire al protocollo di studio.
6. Le pazienti di sesso femminile devono essere in fase di post-menopausa (24 mesi di amenorrea), chirurgicamente sterili o devono acconsentire all’utilizzo di un metodo contraccettivo efficace per tutta la durata dello studio e fino ad un massimo di 120 giorni dopo l’interruzione del trattamento. La contraccezione efficace comprende una terapia ormonale consolidata o un dispositivo intrauterino per le donne, e l’utilizzo di un contraccettivo di barriera (ad es. diaframma o preservativo) con spermicida.

E.4

Principal exclusion criteria

1. Patients with known or suspected hypersensitivity to hzVSF-v13 or to any of its excipients.
2. Active tuberculosis or suspected active bacterial, fungal, viral, or other infection (besides COVID-19).
3. Anti-rejection or immunomodulatory drugs within the past 3 months.
4. Absolute neutrophil count (ANC) < 1000/µL at screening.
5. Platelet count < 50,000/ µL at screening.
6. ALT or AST > 5 x upper limit of normal (ULN) within 24 hours at screening.
7. Serum creatinine > 2 mg/dL (> 176.8 µmol/L) or estimated creatinine clearance < 30 ml/min measured or calculated by Cockroft Gault equation.
8. Pregnancy or breastfeeding.
9. Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization (approved/investigational COVID-19 antivirals and other off-label drugs recommended by local health authorities are permitted).
10. Patients who in the opinion of the treating physician should not participate in this program (ex: severe acute respiratory distress syndrome [ARDS], septicaemia).

1. Pazienti con nota o sospetta ipersensibilità a hzVSF-v13 o ad uno qualsiasi dei suoi eccipienti.
2. Tubercolosi in fase attiva o sospetta infezione batterica, micotica, virale o altra infezione attiva (oltre a COVID-19).
3. Farmaci anti-rigetto o immunomodulanti nei 3 mesi precedenti.
4. Conta assoluta dei neutrofili (Absolute Neutrophil Count – ANC) < 1000/µL allo screening.
5. Conta piastrinica < 50,000/ µL allo screening.
6. ALT o AST > 5x ULN (Upper Limit of Normal – limite superiore di normalità) entro 24 ore allo screening.
7. Creatinina sierica > 2 mg/dL (> 176.8 µmol/L) o clearance della creatinina < 30 ml/min misurata o calcolata tramite l’equazione di Cockroft Gault.
8. Gravidanza o allattamento.
9. Trattamento con un farmaco sperimentale entro 5 emivite o 30 giorni (a seconda di quale dei due periodi sia più lungo) dalla randomizzazione (sono consentiti antivirali approvati/sperimentali per COVID-19 e altri farmaci off-label raccomandati dalle autorità sanitarie locali).
10. Pazienti che, a giudizio del medico, non dovrebbero partecipare a questo programma (ad es. sindrome severa da distress respiratorio acuto [Acute Respiratory Distress Syndrome – ARDS], setticemia.

E.5 End points

E.5.1

Primary end point(s)

Safety endpoints
- Incidence and severity of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
- Change from baseline in vital signs and clinical laboratory test results.
Efficacy endpoints
- Clinical failure at Day 28, defined as any of:
• Death
• Respiratory failure (patient is intubated)
• Patient is in ICU
- Clinical Improvement, defined as a decrease of at least 2 points on the WHO ordinal scale:
0. Uninfected: no clinical or virologic evidence of infection
1. Ambulatory: no limitation of activities
2. Ambulatory: limitation of activities
3. Hospitalized with mild disease: no oxygen therapy
4. Hospitalized with mild disease: oxygen by mask or nasal prongs
5. Hospitalized with severe disease: non-invasive ventilation or high-flow oxygen
6. Hospitalized with severe disease: intubation and mechanical ventilation
7. Hospitalized with severe disease: ventilation + additional organ support: vasopressors, renal replacement therapy, extracorporeal membrane oxygenation
8. Death
- Time to clinical improvement, defined as the time from randomization to clinical improvement as described above.
- Rate of overall survival at Day 28 and Day 60.
- Cumulative mortality rate at Days 7, 14, 21, 28, and 60.
- Time to hospital discharge or “ready for discharge” (i.e. normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or = 2L supplemental oxygen).
Pharmacodynamic endpoint
Serum tumour necrosis factor (TNF)-a, interleukin (IL)-1ß, IL-6 and C-reactive protein (CRP) levels at baseline and at specified times after initiation of study drug. If available, the same assessments are to be performed in BAL samples.

Endpoint di sicurezza
- Incidenza e severità degli eventi avversi in base ai criteri NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v5.0.
- Variazione rispetto al basale dei segni vitali e dei risultati delle analisi di laboratorio clinico.
Endpoint di efficacia
- Insuccesso clinico al Giorno 28, definito come uno qualsiasi dei seguenti:
• Decesso
• Insufficienza respiratoria (il paziente è intubato)
• Il paziente è in ICU
- Miglioramento clinico, definito come una riduzione di almeno 2 punti sulla scala ordinale WHO:
0. Non infetto: nessuna evidenza clinica o virologica di infezione
1. Deambulazione: nessuna limitazione di attività
2. Deambulazione: limitazione di attività
3. Ricoverato con malattia lieve: nessuna ossigenoterapia
4. Ricoverato con malattia lieve: ossigeno somministrato tramite maschera o cannule nasali
5. Ricoverato con malattia severa: ventilazione non invasiva o ossigeno ad alto flusso
6. Ricoverato con malattia severa: intubazione e ventilazione meccanica
7. Ricoverato con malattia severa: ventilazione + supporto aggiuntivo d’organo: vasopressori, terapia renale sostitutiva, ossigenazione a membrana extracorporea (extracorporeal membrane oxygenation)
8. Decesso
- Tempo al miglioramento clinico, definito come il tempo dalla randomizzazione al miglioramento clinico come descritto precedentemente.
- Tasso di sopravvivenza complessiva (rate of overall survival) al Giorno 28 e al Giorno 60.
- Tasso cumulativo di mortalità ai Giorni, 7, 14, 21, 28 e 60.
- Tempo alla dimissione o al momento in cui il paziente è “pronto per la dimissione” (ovvero, temperatura corporea e frequenza respiratoria normali e saturazione di ossigeno stabile in aria ambiente o con ossigeno supplementare = 2L).
Endpoint di farmacodinamica
Livelli di TNF-a (Tumor Necrosis Factor – fattore di necrosi tumorale) sierico, interleuchina (IL)-1ß, IL-6 e proteina C-reattiva (C-Reactive Protein – CRP) al basale e a tempi specifici dopo l’inizio del trattamento in studio. Se disponibili, le stesse valutazioni devono essere effettuate sui campioni di BAL.

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety endpoints
- Up to day 30 after the final dose of the treatment; after this period, only serious adverse events suspected of being related to study treatment are to be reported
- Vital signs up to day 60; laboratory parameters up to day 28.
Efficacy endpoints
- Day 28
- Up to day 60
- Up to day 60
- Day 28 and day 60
- Day 7, 14, 21, 28 and 60
- Up to day 60
Pharmacodynamic endpoint
- Up to day 28

Endpoint di sicurezza
- Fino a 30 giorni dalla ultima dose del trattamento; dopo questo periodo, verranno riportati solamente gli eventi avversi con sospetto correlazione con il trattamento di studio;
- Segni vitali fino a giorno 60; parametri di laboratorio fino al giorno 28.
Endpoint di efficacia
- Giorno 28
- Fino al giorno 60
- Fino al giorno 60
- Giorno 28 e Giorno 60
- Giorni 7, 14, 21, 28 e 60
- Fino al giorno 60
Endpoint di farmacodinamica
- Fino al giorno 28

E.5.2

Secondary end point(s)

- Ventilator-free days to Day 28.
- Organ failure-free days to Day 28.
- Duration of supplemental oxygen.
- SARS-CoV-2 viral clearance over time through nasopharyngeal swab and bronchoalveolar lavage (BAL) samples (if available).

- Giorni liberi da ventilazione al Giorno 28.
- Giorni liberi da insufficienza d’organo al Giorno 28.
- Durata dell’ossigeno supplementare.
- Clearance virale per SARS-CoV-2 nel tempo tramite campioni da tampone nasofaringeo e lavaggio broncoalveolare (Bronchoalveolar Lavage – BAL) (se disponibile).

E.5.2.1

Timepoint(s) of evaluation of this end point

- Day 28
- Day 28
- Up to day 60
- Up to day 28

- Giorno 28
- Giorno 28
- Fino al giorno 60
- Fino al giorno 28

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

Yes

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

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

Information not present in EudraCT

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

Italy

Russian Federation

E.8.7

Trial has a data monitoring committee

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

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:

F.1.3

Elderly (>=65 years)

Yes

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

105

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

Terapia standard

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

2020-12-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-10

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
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