Clinical Trials Register

Summary
EudraCT Number:	2021-000316-31
Sponsor's Protocol Code Number:	HIDR-0721/COV
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-07-30
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

Spain - AEMPS

A.2

EudraCT number

2021-000316-31

A.3

Full title of the trial

Multicenter, double-blind, randomized clinical trial to evaluate the efficacy of calcifediol soft capsules versus placebo in reducing hospital admissions in patients with a positive diagnostic test for SARS-CoV-2.

Ensayo clínico multicéntrico, doble ciego, aleatorizado, para evaluar la eficacia de calcifediol cápsulas blandas versus placebo en la reducción de ingresos hospitalarios en pacientes con prueba diagnóstica positiva para SARS-CoV-2.

A.3.1

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

Clinical trial to evaluate if treatment with calcifediol (vitamin D analog) reduces the number of hospital admissions in patients with COVID-19.

Ensayo Clínico para evaluar si el tratamiento con calcifediol (análogo de la vitamina D) disminuye el número de ingresos en el hospital de pacientes con COVID-19.

A.3.2

Name or abbreviated title of the trial where available

IMMUNOCOVIDIOL

A.4.1

Sponsor's protocol code number

HIDR-0721/COV

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	FAES FARMA S.A.
B.1.3.4	Country	Spain
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	FAES FARMA S.A.
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	Dynamic Science S.L.
B.5.2	Functional name of contact point	Departamento de Operaciones
B.5.3	Address:
B.5.3.1	Street Address	C/ Azcona, 31
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28028
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3491 456 11 05
B.5.5	Fax number	+3491 456 11 26
B.5.6	E-mail	ensayosclinicos@dynasolutions.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	Hidroferol® 0.266 mg soft capsules.
D.2.1.1.2	Name of the Marketing Authorisation holder	FAES FARMA 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.3.1	Product name	Hidroferol
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	Capsule, soft
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

SARS-CoV-2 coronavirus infection (COVID-19).

Infección por el coronavirus SARS-CoV-2 (COVID-19).

E.1.1.1

Medical condition in easily understood language

Coronavirus infection (COVID-19).

Infección por el coronavirus (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 of calcifediol in reducing hospital admissions in patients with a positive result for a diagnostic test for SARS-CoV-2 and at least one risk factor for the development of severe disease.

Evaluar la eficacia de calcifediol en la disminución de ingresos hospitalarios en pacientes con resultado positivo para prueba diagnóstica para SARS-CoV-2 y al menos un factor de riesgo para el desarrollo de enfermedad grave.

E.2.2

Secondary objectives of the trial

1. To evaluate the safety of calcifediol in the treatment of patients with a positive result for SARS-CoV-2 and at least one risk factor.
2. Describe the frequency of admission to the intensive care unit (ICU) in patients with a positive result for SARS-CoV-2 and at least one risk factor, for each treatment group.
3. Describe the frequency of mortality in patients with a positive result for SARS-CoV-2 and at least one risk factor, for each treatment group.
4. Describe the morbidity and mortality in patients with a positive result for SARS-CoV-2 and at least one risk factor, for each treatment group.
5. Describe the evolution of the symptoms related to COVID-19, reported by the patients themselves.

1. Evaluar la seguridad de calcifediol en el tratamiento de pacientes con resultado positivo para SARS-CoV-2 y al menos un factor de riesgo.
2. Describir la frecuencia de ingresos en unidad de cuidados intensivos (UCI) en pacientes con resultado positivo para SARS-CoV-2 y al menos un factor de riesgo, para cada grupo de tratamiento.
3. Describir la frecuencia de mortalidad en pacientes con resultado positivo para SARS-CoV-2 y al menos un factor de riesgo, para cada grupo de tratamiento.
4. Describir la morbimortalidad en pacientes con resultado positivo para SARS-CoV-2 y al menos un factor de riesgo, para cada grupo de tratamiento.
5. Describir la evolución de la sintomatología relacionada a la COVID-19, reportada por el propio paciente.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age: over 18 years old
2. Patient with a suspected respiratory clinical picture of COVID-19, confirmed with a positive result either by PCR for SARS-CoV-2 of nasopharyngeal exudate with or without oropharyngeal exudate; and / or rapid antigen detection test (Antigen Rapid Diagnostic Test, Ag-RDT) of nasal or nasopharyngeal exudate.
The result of any of the diagnostic tests must be available within 72 hours of the onset of the clinical picture.
3. Present at least one of the following risk factors for the development of serious disease:
o Age ≥ 60 years
o Body mass index (BMI) ≥ 30 kg / cm2
o Chronic cardiovascular disease
o Chronic respiratory disease
o Chronic kidney disease
4. Voluntary signing of the Informed Consent (IC).
5. Only for women of reproductive age: availability to perform pregnancy tests; They should also agree to the use of highly effective birth control methods for the entire duration of the study, which include: combined hormonal contraceptives associated with ovulation inhibitors (oral, intravaginal or transdermal), hormonal contraceptives of progesterone associated with inhibitors of the ovulation (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner (if such partner is the only sexual partner of the trial participant and has documentation of azoospermia) or sexual abstinence (defined as avoiding heterosexual sex for the entire risk period associated with trial treatment).
The investigator is responsible for determining whether the patient is using an appropriate birth control method for study participation.

1. Edad: mayores de 18 años
2. Paciente con cuadro clínico respiratorio sospechoso de COVID-19, confirmado con un resultado positivo bien por realización de PCR para SARS-CoV-2 de exudado nasofaríngeo con o sin exudado orofaríngeo; y/o prueba rápida de detección de antígenos (Antigen Rapid Diagnostic Test, Ag-RDT) de exudado nasal o nasofaríngeo.
El resultado de cualquiera de las pruebas diagnósticas debe estar disponible dentro de las 72 horas del inicio del cuadro clínico.
3. Presentar al menos uno de los siguientes factores de riesgo para el desarrollo de enfermedad grave:
o Edad ≥ 60 años
o Índice de masa corporal (IMC) ≥ 30 kg/cm2
o Enfermedad cardiovascular crónica
o Enfermedad respiratoria crónica
o Enfermedad renal crónica
4. Firma voluntaria del Consentimiento Informado (CI).
5. Sólo para mujeres en edad reproductiva: disponibilidad para realizar pruebas de embarazo; asimismo deben acceder al uso de métodos de control de natalidad altamente efectivos durante toda la duración del estudio, los cuales incluyen: anticonceptivos hormonales combinados asociados con inhibidores de la ovulación (oral, intravaginal o transdérmico), anticonceptivos hormonales de progesterona asociados con inhibidores de la ovulación (oral, inyectable o implantable), dispositivo intrauterino (DIU), sistema intrauterino de liberación hormonal, oclusión tubaria bilateral, pareja vasectomizada (en caso que dicha pareja sea la única pareja sexual de la participante en el ensayo y tenga documentación de azoospermia) o abstinencia sexual (definida como evitar relaciones sexuales heterosexuales durante todo el período de riesgo asociado al tratamiento del ensayo).
El investigador es responsable de determinar si la paciente utiliza un método de control de la natalidad adecuado para la participación en el estudio.

E.4

Principal exclusion criteria

1. Subjects who have been treated with calcifediol or cholecalciferol continuously and in doses greater than or equal to 0.266 mg / month or 800 IU / day, respectively, during the last 3 months.
2. Subjects who have taken or are required to take medications that can modify vitamin D levels within the last week before enrollment or during the study: phenobarbital, phenytoin, primidone, digoxin, rifampin, thiazide diuretics (hydrochlorothiazide), some antibiotics (penicillin, neomycin and chloramphenicol), antiretrovirals (tenofovir, adefovir), oral chronic corticosteroids (defined as a dose of prednisolone ≥ 5 mg daily or equivalent) for more than 3 months, verapamil, paraffin, mineral oil laxatives, magnesium salts, actinomycin, and antifungal imidazoles. Subjects taking orlistat, cholestyramine, or colestipol who do not observe a time interval of at least 2 hours with respect to taking study medication.
3. History of hypersensitivity to any of the active ingredients or components of the investigational drug (IM).
4. Subjects who have taken calcium supplements within the last week before inclusion, or who require to take them during the study.
5. Uncorrected hypercalcemia (serum calcium> 10.5 mg / dL), known hypercalciuria, or history of nephrolithiasis.
6. Severe kidney disease, defined by CKD-EPI estimated glomerular filtration rate (GFR) <30 mL / min / 1.73m2
7. Diagnosis of liver failure, exacerbated congestive heart failure, malabsorption, primary hyperparathyroidism, hypoparathyroidism, prolonged immobilization, sarcoidosis, tuberculosis, or other granulomatous diseases.
8. Presence of serious illness that requires direct hospital admission or that due to its characteristics does not allow oral treatment.
9. Persons admitted to an institution by order of judicial authorities or other authorities.
10. People who cannot collaborate with the study procedures.
11. Patients with a current or previous history of neoplasia in the last five years.
12. History of previous hospitalization for COVID-19 or positive diagnostic test for SARS-CoV-2 before the current episode.
13. Women who are pregnant, nursing or planning a pregnancy.
14. Any other medical and / or therapeutic circumstance considered by the researcher that prevents adequate monitoring and / or adequate evolution of the response to the study treatment.
15. Patients who have received an investigational drug (including vaccines) or have used an investigational invasive medical device in the last 30 days prior to the start of the screening phase or are currently participating in another clinical trial.
16. Patients who have received the last dose of any of the approved SARS-CoV-2 vaccines less than 10 days prior to the start of the study; or who have not yet completed the vaccination.
NOTE: If the doctor knows or suspects that the patient does not have the capacity to understand the implications of her participation in the study, he should not allow her to enter without the signature of a legal representative of the same.

1. Sujetos que hayan sido tratados con calcifediol o colecalciferol de forma continuada y en dosis superior o igual a 0,266 mg/mes u 800 UI/día, respectivamente, durante los últimos 3 meses.
2. Sujetos que hayan tomado o requieran tomar medicaciones que puedan modificar los niveles de vitamina D dentro de la última semana antes de la inclusión o durante el estudio: fenobarbital, fenitoína, primidona, digoxina, rifampicina, diuréticos tiazídicos (hidroclorotiazida), algunos antibióticos (penicilina, neomicina y cloranfenicol), antirretrovirales (tenofovir, adefovir), corticosteroides crónicos por vía oral (definido como una dosis de prednisolona ≥ 5 mg al día o equivalente) por más de 3 meses, verapamilo, parafina, laxantes de aceites minerales, sales de magnesio, actinomicina, e imidazoles antifúngicos. Sujetos que tomen orlistat, colestiramina o colestipol que no respeten un intervalo de tiempo de al menos 2 horas con respecto a la toma de la medicación de estudio.
3. Antecedentes de hipersensibilidad a alguno de los principios activos o componentes del medicamento en investigación (MI).
4. Sujetos que hayan tomado suplementos de calcio dentro de la última semana antes de la inclusión, o que requieran tomarlos durante el estudio.
5. Hipercalcemia no corregida (calcio sérico > 10,5 mg/dL), hipercalciuria conocida o antecedentes de nefrolitiasis.
6. Enfermedad renal grave, definida por un filtrado glomerular estimado (FGE) por CKD-EPI <30 mL/min/1,73m2
7. Diagnóstico de fallo hepático, insuficiencia cardiaca congestiva reagudizada, malabsorción, hiperparatiroidismo primario, hipoparatiroidismo, inmovilización prolongada, sarcoidosis, tuberculosis u otras enfermedades granulomatosas.
8. Presencia de enfermedad grave que requiera ingreso hospitalario directamente o que por sus características no permita el tratamiento por vía oral.
9. Personas ingresadas en una institución por orden de autoridades judiciales u otras autoridades.
10. Personas que no puedan colaborar con los procedimientos del estudio.
11. Pacientes con antecedente actual o previo de neoplasia en los últimos cinco años.
12. Antecedente de hospitalización previa por COVID-19 o de prueba diagnóstica positiva para SARS-CoV-2 antes del episodio actual.
13. Mujeres embarazadas, en lactancia o que estén planeando un embarazo.
14. Cualquier otra circunstancia médica y/o terapéutica considerada por el investigador que impida un seguimiento adecuado y/o evolución adecuada de la respuesta al tratamiento del estudio.
15. Pacientes que hayan recibido un fármaco en investigación (incluyendo vacunas) o hayan usado un dispositivo médico invasivo en investigación en los últimos 30 días previos al inicio de la fase de selección o estén actualmente participando en otro ensayo clínico.
16. Pacientes que hayan recibido la última dosis de cualquiera de las vacunas aprobadas para el SARS-CoV-2 en menos de 10 días antes del comienzo del estudio; o que aún no hayan completado la vacunación.
NOTA: Si el médico conoce o sospecha que el paciente no tiene la capacidad de comprender las implicaciones de su participación en el estudio, no debe permitir su ingreso sin la firma de un representante legal del mismo.

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients who, being initially in outpatient follow-up, require hospital admission as a consequence of SARS-CoV-2 infection.

Porcentaje de pacientes que estando inicialmente en seguimiento ambulatorio requieren ingreso hospitalario como consecuencia de infección por SARS-CoV-2.

E.5.1.1

Timepoint(s) of evaluation of this end point

During all the clinical trial period, from the screening to the end of study.

Durante todo el ensayo clínico, desde el screening hasta el final del estudio.

E.5.2

Secondary end point(s)

During all the clinical trial period, from the screening to the end of study.

Durante todo el ensayo clínico, desde el screening hasta el final del estudio.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Percentage of calcifediol-related adverse events
2. Percentage of patients who, being initially in outpatient follow-up, require admission to the ICU as a consequence of SARS-CoV-2 infection.
3. Percentage of patients who die as a result of SARS-CoV-2 infection.
4. Morbidity and mortality rate in patients. Death, hospital admission, or admission to the ICU are considered morbidity and mortality.
5. Change in symptoms related to COVID-19 with respect to baseline and with respect to the days of treatment completed, evaluated using a 5-point Likert scale.

1. Porcentaje de acontecimientos adversos relacionados con calcifediol
2. Porcentaje de pacientes que estando inicialmente en seguimiento ambulatorio requieren ingreso en UCI como consecuencia de infección por SARS-CoV-2.
3. Porcentaje de pacientes que fallecen como consecuencia de infección por SARS-CoV-2.
4. Tasa de Morbimortalidad en los pacientes. Se considera como morbimortalidad el fallecimiento, ingreso hospitalario o el ingreso en UCI.
5. Cambio de la sintomatología relacionada a la COVID-19 con respecto al basal y con respecto a los días de tratamiento cumplidos, evaluada mediante una escala Likert de 5 puntos.

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

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

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

LVLS

Última visita último paciente.

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

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:

804

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

804

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

804

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.

Ninguno.

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

2021-07-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-07-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-08-30

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