Clinical Trials Register

Summary
EudraCT Number:	2020-001890-56
Sponsor's Protocol Code Number:	COVID-Γ
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-07-22
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

Spain - AEMPS

A.2

EudraCT number

2020-001890-56

A.3

Full title of the trial

Double-blind randomized placebo-controlled clinical trial to evaluate the efficacy and safety of the use of intravenous gammaglobulins in the treatment of patients with COVID-19

Ensayo clínico aleatorizado doble ciego comparado con placebo para evaluar la eficacia y seguridad del uso de Gammaglobulinas por vía endovenosa en el tratamiento de pacientes con COVID-19

A.3.1

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

Clinical trial to evaluate the efficacy and safety of gammaglobulins in COVID-19 treatment

Ensayo clínico para evaluar la eficacia y seguridad de gammaglobulinas en el tratamiento de la COVID-19

A.4.1

Sponsor's protocol code number

COVID-Γ

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	Universidad Católica de Murcia (UCAM)
B.1.3.4	Country	Spain
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	Universidad Católica de Murcia
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bioithas, S.L.
B.5.2	Functional name of contact point	Bioithas
B.5.3	Address:
B.5.3.1	Street Address	Parque Cientifico de Alicante. Edificio Naves Incubadoras
B.5.3.2	Town/ city	San Vicente del Raspeig
B.5.3.3	Post code	03690
B.5.3.4	Country	Spain
B.5.6	E-mail	laura.navarro@bioithas.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	Flebogamma (Human normal immunoglobulin (IVIg)) One ml contains: Human normal immunoglobulin,100mg ((purity of at least 97% IgG)
D.2.1.1.2	Name of the Marketing Authorisation holder	Instituto Grifols, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Concentrate 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	Gammaglobuline
D.3.9.1	CAS number	8000010-96-0
D.3.9.3	Other descriptive name	GAMMA GLOBULIN
D.3.9.4	EV Substance Code	SUB13945MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/l milligram(s)/litre
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with severe symptoms of COVID-19, a disease caused by infection with the SARS-CoV-2 virus.

Pacientes con síntomas graves de COVID-19, una enfermedad causada por una infección con el virus SARS-CoV-2.

E.1.1.1

Medical condition in easily understood language

Patients with severe COVID-19 disease.

Pacientes con enfermedad grave de COVID-19.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

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 efficacy and safety of using intravenously administered gammaglobulin as treatment in patients with COVID-19.

Evaluar la eficacia y seguridad del uso de gammaglobulina administrada por vía endovenosa como tratamiento en pacientes COVID-19.

E.2.2

Secondary objectives of the trial

To evaluate the impact of the treatment on the clinical situation of the patients and on the inflammation markers at the end of the study period.

Evaluar el impacto del tratamiento sobre la situación clínica de los pacientes y sobre los marcadores de inflamación al finalizar el periodo de estudio.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Adults 18 years of age or over.

- SARS-CoV-2 infection confirmed by PCR technique from samples of the nasopharynx and / or sputum and / or the upper respiratory tract.

- Interval between the onset of symptoms and randomization greater than or equal to 5 days. The onset of symptoms is mainly based on fever. If there is no fever, cough or other related symptoms may be used.

- Patients with a diagnosis of multilobar pneumonia attributed to SARS-Cov-2 infection and diagnosed by chest X-ray or CT.

- At least one of the following conditions: respiratory distress, Respiratory Rate (RF) ≥ 30 times / min; oxygen saturation ≤ 90% at rest; PaO2 / FiO2 ratio ≤ 300 mmHg; respiratory failure with a clinical situation that in clinical judgment requires mechanical ventilation; shock situation; requiring monitoring and ICU treatment due to the patient's clinical situation.

- At least one of the following conditions: levels above the normal range in a peripheral blood sample of: Ferritin, D-Dimer, Procalcitonin and IL-6.

- Signing the informed consent on a voluntary basis.

- Adultos de una edad igual o superior a 18 años.

- Infección por SARS-CoV-2 confirmada mediante técnica de PCR a partir de muestras de nasofaringe y/o esputo y/o del tracto respiratorio superior.

- Intervalo entre el inicio de los síntomas y la aleatorización mayor o igual a los 5 días. La aparición de los síntomas se basa principalmente en la fiebre. Si no hay fiebre, se pueden usar tos u otros síntomas relacionados.

- Pacientes con diagnóstico de neumonía multilobar atribuida a la infección por SARS-Cov-2 y diagnosticada por Rx de tórax o TAC.

- Al menos una de las siguientes condiciones: dificultad respiratoria, Frecuencia Respiratoria (FR) ≥ 30 veces/min; saturación de oxígeno ≤ 90% en estado de reposo; cociente PaO2/FiO2 ≤ 300 mmHg; insuficiencia respiratoria con situación clínica que a criterio clínico requiere de ventilación mecánica; situación de shock; que requiera monitorización y el tratamiento en UCI consecuencia de la situación clínica del paciente.

- Al menos una de las siguientes condiciones: niveles por encima del rango de la normalidad en los valores basales en muestra de sangre periférica de: Ferritina, Dímero D, Procalcitonina e IL-6.

- Firma del consentimiento informado de forma voluntaria.

E.4

Principal exclusion criteria

- There are other culture microbiological evidences, antigen study or serology that can explain pneumonia, which include, but are not limited to: influenza A virus, influenza B virus, bacterial pneumonia, fungal pneumonia or suspect a non-infectious process.

- Allergy to intravenous immunoglobulin or its preparation components.

- Patients with selective IgA, IgM or IgG deficiency or another condition that makes the patients unsuitable for study therapy.

- Pregnant or lactating women.

- That the investigators consider it inappropriate to clinical criteria and other circumstances in which the investigator determines that the patient is not suitable for the clinical trial.

- Existen otras evidencias microbiológicas por cultivo, estudio de antígenos o serología que pueden explicar la neumonía, que incluyen, pero no se limitan a: virus de influenza A, virus de influenza B, neumonía bacteriana, neumonía fúngica o bien sospecha de un proceso no infeccioso.

- Alergia a la inmunoglobulina intravenosa o sus componentes de preparación.

- Pacientes con deficiencia selectiva de IgA, IgM o IgG u otra condición que hace que los pacientes no sean adecuados para la terapia del estudio.

- Mujeres embarazadas o en periodo de lactancia.

- Que los investigadores lo consideran inadecuado a criterio clínico y otras circunstancias en las que el investigador determine que el paciente no es apto para el ensayo clínico.

E.5 End points

E.5.1

Primary end point(s)

1. Mortality, that is, number of deaths.

1. Mortalidad, es decir, número de muertes.

E.5.1.1

Timepoint(s) of evaluation of this end point

End point 1: Between 0- and 28-days.

End point 1: Entre los días 0 y 28.

E.5.2

Secondary end point(s)

2. Clinical improvement of 2 points or more, based on a 7-point scale.

3. Proportion of patients with negative RT-PCR results.

4. Duration, in days, of mechanical ventilation.

5. Duration, in days, of hospitalization, that is, days the patient stays in the hospital.

6. Duration, in days, of the stay in the Intensive Care Unit.

7. Changes in inflammation markers: Ferritin, D-Dimer, Procalcitonin, Interleukin-6.

8. Number of days of receiving the prescribed medication to treat COVID-19 infection (hydroxychloroquine, antivirals, steroids, immunomodulators, monoclonal antibodies and / or others).

9. Frequency of occurrence of adverse events, due or not to the intervention.

10. Frequency of occurrence of serious adverse events, due or not to the study intervention.

2. Mejora clínica de 2 puntos o más, basada en una escala de 7 puntos.

3. Proporción de pacientes con resultados negativos de RT-PCR.

4. Duración, en días, de la respiración asistida.

5. Duración, en días, de la hospitalización, es decir, días que el paciente permanece en el hospital.

6. Duración, en días, de la permanencia en la Unidad de Cuidados Intensivos.

7. Cambios en los marcadores de inflamación: Ferritina, Dímero D, Procalcitonina, Interleucina- 6.

8. Número de días que reciben el medicamento prescrito para tratar la infección COVID-19 (hidroxicloroquina, antivirales, esteroides, inmunomoduladores, anticuerpos monoclonales y/o otros).

9. Frecuencia de aparición de acontecimientos adversos, debidos o no a la intervención.

10. Frecuencia de aparición de acontecimientos adversos graves, debidos o no a la intervención en estudio.

E.5.2.1

Timepoint(s) of evaluation of this end point

End point 2: At 7-, 14- and 28-days after randomization.

End point 3: At 7-, 14- and 28-days after randomization.

End point 4: Between 0- and 28-days.

End point 5: Between 0- and 28-days.

End point 6: Between 0- and 28-days.

End point 7: At 7- and 14-days after randomization.

End point 8: Between 0- and 28-days.

End point 9: Between 0- and 28-days.

End point 10: Between 0- and 28-days.

End point 2: A los 7, 14 y 28 días después de la aleatorización.

End point 3: A los 7, 14 y 28 días después de la aleatorización.

End point 4: Entre los días 0 y 28.

End point 5: Entre los días 0 y 28.

End point 6: Entre los días 0 y 28.

End point 7: A los 7 y 14 días después de la aleatorización.

End point 8: Entre los días 0 y 28.

End point 9: Entre los días 0 y 28.

End point 10: Entre los días 0 y 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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

LVLP

Only in case of inability to include the 100 expected patients, the IPs of each center will meet to decide whether or not to finish the study with the number included until this moment, provided that at least 70% of theplanned cases have been reached

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

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

100

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

2020-06-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-06

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

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