Clinical Trials Register

Summary
EudraCT Number:	2020-000982-18
Sponsor's Protocol Code Number:	NOR-SOLIDARITY
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-03-24
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

Norway - NOMA

A.2

EudraCT number

2020-000982-18

A.3

Full title of the trial

The NOR Solidarity multicenter trial on the efficacy of different anti-viral drugs in SARS-CoV-2 infected patients (COVID-19).

A.3.1

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

A clinical study to evaluate the efficacy of different anti-viral drugs in SARS-CoV-2 infected patients (COVID-19).

A.3.2

Name or abbreviated title of the trial where available

NOR-SOLIDARITY

A.4.1

Sponsor's protocol code number

NOR-SOLIDARITY

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	Oslo University Hospital
B.1.3.4	Country	Norway
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	Oslo university hospital
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Oslo university hospital
B.5.2	Functional name of contact point	Sect. Clin. Imm. & Infect. Diseases
B.5.3	Address:
B.5.3.1	Street Address	Sognsvannsveien 20
B.5.3.2	Town/ city	Oslo
B.5.3.3	Post code	0372
B.5.3.4	Country	Norway
B.5.4	Telephone number	+4723071916
B.5.6	E-mail	andreas.barrattdue@gmail.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	Yes
D.2.1.1.1	Trade name	Plaquenil
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-aventis Norge
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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	Plaquenil
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	hydroxychloroquine sulphate
D.3.9.1	CAS number	747-36-4
D.3.9.3	Other descriptive name	HYDROXYCHLOROQUINE SULFATE
D.3.9.4	EV Substance Code	SUB02587MIG
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	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	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	Remdesivir
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.3.9.3	Other descriptive name	Remdesivir
D.3.9.4	EV Substance Code	SUB195655
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	100
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)	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

SARS-COV-2 infection

E.1.1.1

Medical condition in easily understood language

Coronavirus disease

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	LLT
E.1.2	Classification code	10037373
E.1.2	Term	Pulmonary disorder
E.1.2	System Organ Class	100000004855

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 investigate the effect of Remdesivir and Hydroxychloroquine on all-cause in-hospital mortality compared to standard of care.

E.2.2

Secondary objectives of the trial

- To assess the effect of Remdesivir and Hydroxychloroquine treatment on hospital duration, receipt of ventilation or intensive care, and to identify any serious adverse reactions.
- To assess the effect of Remdesivir and Hydroxychloroquine treatment on 28 days mortality, viral clearance, kidney and myocardial failure, co-infections, organ dysfunction and health-related Quality of Life.

Exploratory:
Assess the effect of Remdesivir and Hydroxychloroquine on biomarkers and safety.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

POPulation PharmacoKinetic (POPPK) study of antiviral drugs in SARS-CoV-2 infected patients participating in The Investigational NOR-SOLIDARITY study. Version 6, 28 April 2020.

Primary objective:
To develop novel population pharmacokinetic models for Remdesivir and Hydroxychloroquine in moderate/severe COVID-19 patients.

Explorative objective:
Assess viral decay, CRP/ IL-6 levels, SUSARs and Grade 3 and 4 AEs, myocardial failure/ QT-time prolongation, eGFR reduction of > 50% from baseline.

E.3

Principal inclusion criteria

1. Adult patients, 18 years and above
2. Confirmed SARS-2-CoV-2 infection by PCR
3. Admitted to the hospital ward or the ICU
4. Subjects (or legally authorized representative) provides written informed consent prior to initiation of the study
5. No anticipated transfer within 72 hours to a non-study hospital

E.4

Principal exclusion criteria

1. Severe co-morbidity with life expectancy <3 months according to investigators assessment
2. ASAT/ALAT > 5 times the upper limit of normal
3. Acute co-morbidity within 7 days before inclusion such as myocardial infarction
4. Known intolerance and hypersensitivity to any of the components of the available study drug.
5. Pregnancy or breast feeding
6. Any reason why, in the opinion of the investigators, the patient should not participate
7. Participation in a potentially confounding drug or device trial during the course of the study
8. Prolonged QTc interval (>470 ms)
9. Already receiving any of the study drugs
10. Patients with psoriasis
11. Patients on concomitant medication which is part of the list of prohibited medications have to be excluded from the current study (see protocol section 4.3)

E.5 End points

E.5.1

Primary end point(s)

All-cause in-hospital mortality.

E.5.1.1

Timepoint(s) of evaluation of this end point

During hospitalisation.

E.5.2

Secondary end point(s)

During hospitalisation:
- Receipt of mechanical ventilation
- Time to first receiving and duration of mechanical ventilation
- Receipt of intensive care
- Duration of intensive care
- Occurrence of Suspected Unexpected Serious Adverse Reactions (SUSARs)

During hospitalisation:
- Viral clearance as assessed by SARS-CoV 2 PCR in oropharyngeal specimens during hospitalization
- Occurence of kidney failure (eGFR <40 mL/min)
- Occurence of myocardial involvement assessed by biochemical markers as well as echocardiography measuring left ventricular ejection fraction within the first week
- Occurence of co-infections (super infections with bacteria, fungi and other virus)

Assessed after 28 days:
- Overall survival
- Patient reported respiratory health status by CAT (Chronic Obstructive Pulmonary Disease (COPD) assessment Test) score

Assessed after 3 months:
- Occurence of systolic and diastolic cardiac dysfunction and level of remodelling asssessed by echocardiography and biochemical markers
- Occurence of pulmonary dysfunction and level of fibrosis assessed by spirometry and thoracic CT scan
- Health related quality of life assessed by the RAND 36-item Short Form Health Survey (SF-36) item scores and the 5-dimension EuroQol (EQ-5D) questionnaires index value.

Exploratory:
Biomarkers during hospitalisation and after 3 months
- Inflammatory and anti-inflammatory mediators as assessed in serum and plasma
- Markers of extracellular matrix remodelling
- Markers of endothelial activation
- Markers of platelet activation
- Cellular immunity
- Prognostic biosignatures (RNA)
- Gut microbiota assessed by rectal swab
- Pharmacokinetics during hospitalization
- Adverse events during hospitalization

E.5.2.1

Timepoint(s) of evaluation of this end point

Please see above

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Standard of 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

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

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:

609

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

609

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

When the patient lacks the capacity to consent to participation, an appropriate representative will be approached by staff trained in consent procedures that protect the rights of the patient, and adhere to the Declaration of Helsinki.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

1218

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

2020-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-13

P. End of Trial
P.	End of Trial Status	Ongoing

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