Clinical Trials Register

Summary
EudraCT Number:	2020-001886-35
Sponsor's Protocol Code Number:	RHMCRI0399
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-05-11
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

UK - MHRA

A.2

EudraCT number

2020-001886-35

A.3

Full title of the trial

A clinical trial of nebulized surfactant for the Treatment of moderate to severe COVID-19 in adults

A.3.1

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

A Clinical Trial of Nebulized Bovactant (Alveofact ®) for the Treatment of Moderate to Severe COVID-19

A.3.2

Name or abbreviated title of the trial where available

COVID-19 Surfactant Clinical Trial

A.4.1

Sponsor's protocol code number

RHMCRI0399

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04362059

A.5.4

Other Identifiers

Name:

MHRA Correspondence

Number:

E/2020/0772

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	University Hospital Southampton NHS Foundation Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bill & Melinda Gates Foundation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Hospital Southampton NHS Foundation Trust
B.5.2	Functional name of contact point	Mike Grocott
B.5.3	Address:
B.5.3.1	Street Address	Southampton General Hospital, Tremona Road
B.5.3.2	Town/ city	Southampton
B.5.3.3	Post code	SO16 6YD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02381208449
B.5.6	E-mail	mike.grocott@soton.ac.uk

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	Alveofact®
D.2.1.1.2	Name of the Marketing Authorisation holder	Lyomark Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Alveofact®
D.3.4	Pharmaceutical form	Powder for nebuliser suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Endotracheopulmonary use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SF-RI 1
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	45
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COVID-19 infection in patients requiring endotrachael intubation

E.1.1.1

Medical condition in easily understood language

Coronavirus infection in patients requiring endotrachael intubation

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	10051905
E.1.2	Term	Coronavirus infection
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 whether administration of surfactant therapy via the modified Aerogen nebuliser results in improved PaO2/FiO2 ratio and ventilation index in patients with COVID-19 after last dose of surfactant and the optimal dosing schedule to be used.

E.2.2

Secondary objectives of the trial

To assess the safety of surfactant therapy via the modified Aerogen nebuliser and mean clinical improvement of patients with COVID-19 following administration.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥18 years old
2. Confirmed COVID-19 positive by PCR
3. Within 24 hours of mechanical ventilation
4. Assent obtained from personnel (PerLR) or professional legal representative (ProfLR)

E.4

Principal exclusion criteria

1. Imminent expected death within 24 hours
2. Specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary haemorrhage)
3. Known or suspected pregnancy
4. Stage 4 severe chronic kidney disease or requiring dialysis (i.e., eGFR < 30)
5. Liver failure (Child-Pugh Class C)
6. Anticipated transfer to another hospital, which is not a study site within 72 hours.
7. Current participation or participation in another study within the last month that in the opinion of the investigator would prevent enrollment for safety purposes.
8. Consent declined

E.5 End points

E.5.1

Primary end point(s)

Change in PaO2/FiO2 ratio at 48 hours after study initiation.

Change in the Ventilation Index at 48 hours after study initiation.

E.5.1.1

Timepoint(s) of evaluation of this end point

48 hours after study initiation

E.5.2

Secondary end point(s)

The key secondary endpoint is safety over the first 29 days after administration of surfactant assessed by:
• Cumulative incidence of serious adverse events (SAEs)
• Cumulative incidence of Grade 3 and 4 adverse events (AEs).
• Cumulative incidence of AEs.
• Changes in white cell count, hemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, and AST over time.

Other secondary endpoints are:
• Change in PaO2/FiO2 after last dose of surfactant at 24 and 48 hours after study initiation
• Change in ventilatory index value at 24 and 48 hours after study initiation
• Change in pulmonary compliance (L/cmH2O) at 24 and 48 hours after study initiation
• Change in PEEP requirement at 24 and 48 hours after study initiation
• Number of days on mechanical ventilation after last dose of surfactant
• Number of days hospitalized after last dose of surfactant
• Ordinal outcome after last dose of surfactant assessed daily while hospitalized and on Days 15 and 28
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.
• Ventilation days, every day after study initiation
• Ventilator Free days, every day after study initiation until day 21
• Intensive Unit Care length of stay, every day after study initiation
• Number of Hospital Days, every day after study initiation
• 28-day mortaility, on day 28 after the study initiation

E.5.2.1

Timepoint(s) of evaluation of this end point

Ongoing safety analysis up until day 28 after administration of the first dose of surfactant.
Hospitalisation and ventilator requirements - ongoing analysis up until day 28 after administration of the first dose of surfactant.
Change in pulmonary compliance (L/cmH20) at 24 and 48 hours after study initiation.
Daily assessment of clinical outcome after the last dose of surfactant whilst hospitalised.

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Standard care

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

The completion of the testing of samples. This will be achieved no later than 3 months after 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