Clinical Trials Register

Summary
EudraCT Number:	2020-001052-18
Sponsor's Protocol Code Number:	010
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-03-20
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

Denmark - DHMA

A.2

EudraCT number

2020-001052-18

A.3

Full title of the trial

A Multicenter, Adaptive, Randomised Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults - Version for European Union/United Kingdom Sites

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

Adaptive COVID-19 Treatment Trial in the EU & UK (ACTT-EU/UK)

A.4.1

Sponsor's protocol code number

010

A.5.4

Other Identifiers

Name:

DMID - NIH

Number:

20-0006, Version no. 6.0

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	Regents of the University of Minnesota
B.1.3.4	Country	United States
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	National Institute of Health
B.4.2	Country	United States
B.4.1	Name of organisation providing support	University of Minnesota
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	United States NIAID, Division of Microbiology and Infectious Diseases (DMID) National Institute of Health (NIH)
B.5.2	Functional name of contact point	Janice Arega
B.5.3	Address:
B.5.3.1	Street Address	5601 Fishers Lane
B.5.3.2	Town/ city	Bethesda
B.5.3.3	Post code	20892
B.5.3.4	Country	United States
B.5.4	Telephone number	+1240292-0928
B.5.5	Fax number	+1301480-3579
B.5.6	E-mail	aregaj@niaid.nih.gov

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	REMDESEVIR
D.3.2	Product code	GS-5734
D.3.4	Pharmaceutical form	Lyophilisate for 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	REMDESIVIR
D.3.9.2	Current sponsor code	GS-5734
D.3.9.4	EV Substance Code	SUB195655
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	5
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.IMP: 2
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	Olumiant
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland B.V. Papendorpsweg 83, 3528BJ, Utrecht, The Netherlands
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Olumiant
D.3.2	Product code	LY3009104
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.8	INN - Proposed INN	BARICITINIB
D.3.9.2	Current sponsor code	LY3009104
D.3.9.3	Other descriptive name	BARICITINIB
D.3.9.4	EV Substance Code	SUB180983
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	2
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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
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

Influenza COVID-19

E.1.1.1

Medical condition in easily understood language

Influenza 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	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10022005
E.1.2	Term	Influenza viral infections
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 evaluate the clinical efficacy, as assessed by time to recovery or different investigational therapeutics as compared to the control arm.

E.2.2

Secondary objectives of the trial

Key Secondary: To evaluate the clincial efficacy of different investigational therapeutics relative to the control arm in adults hospitalised with COVID-19 accroding to clinical status (8-point scale) at Day 15.
Additional secondary:
1. To evaluate the clinical efficaty of different invesitgational therapeutics as compared to the control arm assessed by: Clinical Severity, NEWS, Oxygenation, Non-invasive ventilation/high flow oxygen, Invasive Mechanical Ventilation/ECMO, Hospitalisation, Mortality: 14-day, 28-day.
2. To evaluate the safety of different investigational therapeutics as compared to the control arm as assessed by:
Commulative incidence of SAE thorough Day 29, Commulative incidence of Grade 3 and 4 clincial and/or laboratory AEs through Day 29
Discontinuation or temporary suspension of infusions, Changes in laboratory values over time (analysis of lab. values in addition to AEs noted above
Exploratory with stored samples (separate consent required)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Admitted to a hospital with synmptoms suggestive of COVID-19 infection
2. Subject (or legally authorised representative) provides informed consent prior to initiation of any study procedures
3. Subject (or legally authorised representative) understands and agrees to comply wiht planned study procedures
4.Male or non-pregnant female adult ≥ 18 years of age at time of enrollment
5. Has laboratory - confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen as documented by either of the following: PCR positive in sample collected < 72 hours prior to randomisation OR PCR positive in sample collected ≥ 72 hours prior to randomisation, documented inabilty to obtain a repeat sample (e.g. due to lack of testing supplies limited testing capacity, results taking > 24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection
6. Illness of any duaration, and at least one of the following:
Radiographic infiltrates by imagin (chest X-ray, CT-scanm etc.) OR SpO2 ≤ 94% on room air, OR Requiring supplemental oxygen, OR Requiring mechanical ventilation or ECMO
7. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not incluidng hormonal contraception from the time of screening through Day 29
8. Agrees to not participate in another clinical trial for treatment of COVID-19 or SARS-CoV-2 thorugh Day 29

E.4

Principal exclusion criteria

1. ALT/AST > 5 times the upper limit of normal
2. Estimated glumerular filtration rate (eGFR) < 30 ml/min or patientes receiving hemodialysis or hemofiltration at time of screening
3. Neutropenia (absolute neutrophil count < 1000 cells/µL) (<1.0 x 103/µL, or <1.0 GI/L)
4. Lymphopenia (absolute lymphocyte count <200 cells/µL) (<0.20 x 103/µL or < 0.20 GI/L)
5. Pregnancy or breast feeding
6. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours
7. Allergy to any study medication
8. Received three or more doses of remdesivir including the loadingdose, outside of the study under the EUA (or similar mechanism) for COVID-19
9. Received convalesent plasma or intravenous immunoglobulin (IVIg]) for COVID-19 the current ilness for which they are being enrolled
10. Received small molecule tyrosin kinase inhibitors (e.g. baricitinib, imatibib, genfinitib) in the 1 week prior to screening
11. Received monoclonal antibodies targeting cytokines (e.g. TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab]) or cells (e.g. abatacept) im the 4 weeks prior to screening
12. Received moniclonal antibodies targeting B-cell (e.g. rituximab and including any targeting multiple cell lines including B-cells) in the 23 month prior to screening
13. Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with baricitinib is larger thatn the risk of COVID-19
14. Received ≥ 20 mg/day of prednisolone or equivalent for ≥14 consecutive days in the 4 weeks prior to screening.
15. Use of probenecid that cannot be discontinued at study enrollment.
16. Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
17. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.
18. Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects.
19. Have a history of VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 12 weeks prior to screening or have a history of recurrent (>1) VTE (DVT/PE).
20. Immunocompromised patients, patients with a chronic medical condition, or those taking a medication that cannot be discontinued at enrollment, who, in the judgment of PI, are at increased risk for serious infections or other safety concerns given the study products.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoints:
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale:
Hospitalised, not requireing supplemental oxygen - no longer requires ongiong medical care
Not hospitalised, limitation on activities and/or requiering home oxygen
Not hospitalised, no limitations on activities
Recovery is evaluated up until Day 29
Key Secondary:
Death
Hospitalised on invasive mechanical ventilation or ECMO
Hospitalised on non-invasive ventilation or high flow oxygen devices
Hospitalised, requiring supplemental oxygen
Hospitallised, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalised, not requiring supplemental oxygen - no longer requires ongoing medical care
Not hospitalised, limitation on activities and/or requiring home oxygen
Not hospitalised, no limitations on activities

E.5.1.1

Timepoint(s) of evaluation of this end point

Subjects will be assessed daily while hospitalised.
If the subjects discharged from the hospital they will have a study visit at Days 15, 22 and 29.
For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and (for consenting subjects) OP swab and blood (serum only) samples for secondary research as well as clinical outcome data.
The day 22 vist is conducted by phone

E.5.2

Secondary end point(s)

Clinical outcome assessed using ordinal scale daily while hospitalised and on Days 15, 22 and 29
NEWS assessed daily while hospitalised and on Day 15 and 29
Days of supplemental oxygen (if applicable) up to Day 29
Days of non-invasive ventilation/high flow oxygen (if applicable) up to Day 29
Days of invasive mechanical ventilation/ECMO (if applicable) up to Day 29
Days of hospitalisation up to Day 29
Date and cause of death (if applicable)
SAEs
Grade 3 and 4 AEs
WBC, with differential, haemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, AST, INR, d-dimer, CRP on Day 1, days 3, 5, 8 and 11 (while hospitalized) and Day 15 and 29 (if attends in-person visit or still hospitalized)

E.5.2.1

Timepoint(s) of evaluation of this end point

Subjects will be assessed daily while hospitalised.
If the subjects discharged from the hospital they will have a study visit at Days 15, 22 and 29.
For discharged subjects, it is preferred that athe Day 15 and 29 visits are in person to obtain safety laboratory tests and (for consenting subjects) OP swab and blood (serum only) samples for secondary research as well as clinical outcome data.
The day 22 vist is conducted by phone

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)

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

Yes

E.8.1.7.1

Other trial design description

Adaptive

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

Denmark

Germany

Greece

Poland

Spain

United Kingdom

United States

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 years

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:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

400

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

300

F.4.2.2

In the whole clinical trial

800

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
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	INSIGHT (International Network for Strategic Initiatives in Global HIV Trials)
G.4.3.4	Network Country	United States

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-03-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-09-10

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