Clinical Trials Register

Summary
EudraCT Number:	2018-003427-11
Sponsor's Protocol Code Number:	PRO-RCT-ACAROS-2018-01
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:	2021-06-14
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

2018-003427-11

A.3

Full title of the trial

Efficacy and safety assessment of a subcutaneous immunotherapy (Beltavac®) with polymerized allergenic extract from house dust mites in patients with allergic rhinitis/rhinoconjuntivitis

Evaluación de la eficacia y seguridad de la inmunoterapia subcutánea (Beltavac®) con extracto alergénico polimerizado de mezcla de ácaros del polvo en pacientes con rinitis/rinoconjuntivitis alérgica

A.3.1

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

N/A

A.4.1

Sponsor's protocol code number

PRO-RCT-ACAROS-2018-01

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	Probelte Pharma S.L.U.
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	NA
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	Probelte Pharma
B.5.2	Functional name of contact point	Medical Affairs
B.5.3	Address:
B.5.3.1	Street Address	NA
B.5.3.2	Town/ city	NA
B.5.3.3	Post code	NA
B.5.3.4	Country	Spain
B.5.6	E-mail	inmaculadabuendia@probeltepharma.es

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	Beltavac® with polymerized extract from Dermatophagoides
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	House dust mites allergoid from Dermatophagoides pteronyssinus and Dermatophagoides farinae
D.3.9.3	Other descriptive name	HOUSE DUST MITES ALLERGEN EXTRACTS (CHEMICALLY MODIFIED)
D.3.9.4	EV Substance Code	SUB187925
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
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)	Yes
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 injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Allergic rhinitis/ rhinoconjuntivitis associated or not with asthma

rinitis/rinoconjuntivitis alérgica asociada o no con asma

E.1.1.1

Medical condition in easily understood language

House dust mite allergy

Alergia a los ácaros del polvo

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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	10001724
E.1.2	Term	Allergic rhinitis (excl hay fever)
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 assess the efficacy of Beltavac® with polymerized dust mite extract measured by the combined scale of nasal symptoms and specific allergy medication completed by the patient daily in periods of 4 weeks repeatedly for a year.

Evaluar la eficacia de Beltavac® con extracto polimerizado de ácaros del polvo utilizando la escala combinada de síntomas nasales y medicación específica de alergia completada por el paciente diariamente en periodos de 4 semanas de forma repetida durante un año.

E.2.2

Secondary objectives of the trial

To assess the efficacy of of Beltavac® with polymerized dust mite extract measured by the impact on:
-the combined scale of nasal and ocular symptoms and specific allergy medication completed by the patient daily in periods of 4 weeks repeatedly for a year.
- the global allergy symptoms, rhinitis control and quality of life at baseline and after 6 and 12 months of treatment.
- serological levels of specific antibodies at baseline and after 6 and 12 months of treatment.
To assess the safety of of Beltavac® with polymerized dust mite extract measured during the study period.
To assess the impact of IMP on health economics during the study period.

Evaluar la eficacia de Beltavac® con extracto polimerizado de ácaros del polvo utilizando:
- la escala combinada de síntomas nasales y oculares y medicación específica de alergia completada por el paciente diariamente en periodos de 4 semanas de forma repetida durante un año.
-los síntomas globales de alergia, el control de los síntomas de rinitis y la calidad de vida evaluados en visita basal y tras 6 y 12 meses de tratamiento.
-los niveles de inmunoglobulinas específicas en suero en visita basal y tras 6 y 12 meses de tratamiento.
Evaluar la seguridad de Beltavac® con polimerizado de ácaros del polvo durante el periodo estudio.
Evaluar el impacto del medicamento en investigación en la economía de la salud durante el periodo de estudio.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Written informed consent, signed and duly dated.
Man or woman between 12 and 65 years old (both included).
Patient with moderate or severe symptoms of persistent rhinitis according to the ARIA Guide, associated or not with well or partially controlled asthma according to the GEMA 5.0 Guide.
Confirmation of sensitization to DPT or DF with a positive prick test (mean papule diameter greater than or equal to 3 mm) with a commercial standardized allergenic extract and a serum extract-specific IgE value of class 3 or higher (> 3.5 kU / L) within the 6 months prior to the study.
Negative pregnancy test.
Nasal symptom and medication combined scale score ≥ 1.5 during the screening phase.

Consentimiento informado por escrito, firmado y fechado debidamente.
Hombre o mujer entre 12 y 65 años (ambos incluidos).
Paciente con síntomas moderados o graves de rinitis persistente según la Guía ARIA asociados o no a asma bien o parcialmente controlada según la Guía GEMA 5.0.
Confirmación de sensibilización a DPT o DF con un “prick test” positivo (diámetro medio de la pápula mayor o igual a 3 mm) con un extracto alergénico estandarizado comercial y un valor de IgE específica del extracto en suero de clase 3 o superior (>3,5 kU/L) dentro de los 6 meses anteriores al estudio.
Test de embarazo negativo.
Puntuación de la escala combinada de síntomas nasales y medicación ≥ 1,5 durante la fase de selección.

E.4

Principal exclusion criteria

Concomitant sensitization to allergens other than dust mites if clinically relevant symptoms are anticipated that may interfere with study evaluation periods at the discretion of the investigator.
Poorly controlled asthma according to the GEMA 5.0 guideline
Severe asthma, that is, those who during the last months have controlled their asthma according to therapeutic step 5-6 of the GEMA 5.0 guideline.
Autoimmune diseases or immunodeficiency.
Malignant neoplasms, serious cardiovascular disease, serious mental illness or other relevant chronic diseases that may interfere with the results of the study.
Clinical history of anaphylaxis with cardio / respiratory symptoms.
Hypersensitivity to any of the excipients of the investigational product.
Immunosuppressive medication during the last 6 months before the inclusion of patients and until the end of the study.
Treatment with beta-blockers during the study.
Patients who have previously received immunotherapy with allergenic dust mite extract or other extracts and have failed within the last 5 years.
Patients with immunotherapy with allergens other than dust mites during the study period.
Patients who receive any other vaccine one week before the start of treatment or awaiting the second dose of vaccine against COVID-19.
Pregnant or nursing patients.

Sensibilización concomitante a otros alérgenos diferentes a los ácaros del polvo en caso de que se prevean síntomas clínicamente relevantes que puedan interferir con los periodos de evaluación del estudio según el criterio del investigador.
Asma mal controlada según la guía GEMA 5.0
Asma grave, es decir, aquellos que durante los últimos meses han controlado su asma según el escalón terapéutico 5-6 de la Guía GEMA 5.0.
Enfermedades autoinmunes o inmunodeficiencia.
Neoplasias malignas, enfermedades cardiovasculares graves, enfermedades mentales graves u otras enfermedades crónicas relevantes que puedan interferir con los resultados del estudio.
Historial clínico de anafilaxis con síntomas cardio/respiratorios.
Hipersensibilidad a cualquiera de los excipientes del producto en investigación.
Medicación inmunosupresora durante los últimos 6 meses antes de la inclusión de pacientes y hasta el fin del estudio.
Tratamiento con betabloqueantes durante el estudio.
Pacientes que hayan recibido inmunoterapia con extracto alergénico de ácaros del polvo anteriormente u otros extractos y que haya fracasado durante los últimos 5 años.
Pacientes con inmunoterapia con otros alérgenos que no sean ácaros del polvo durante el periodo del estudio.
Pacientes que reciban cualquier otra vacuna una semana antes del inicio del tratamiento o en espera de la segunda dosis de vacuna frente a la COVID-19.
Pacientes embarazadas o en lactancia.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the combined nasal symptom and medication score. The symptoms assessed are: itchy nose, sneezing, runny nose, and blocked nose (all rated from 0-3). The medication score is 1 for oral and/or topical antihistamines, 2 for intranasal corticosteroids, and 3 for oral corticosteroids. The scores from the nasal symptoms are added and divided by 4 to a total daily symptom score from 0-3. The total daily medication score ranges from 0-3. The combined nasal symptom and medication score will range from 0-6.

El parámetro principal es la puntuación combinada de síntomas nasales y medicación. Los síntomas evaluados son: picazón en la nariz, estornudos, secreción nasal y congestión nasal (todos clasificados de 0 a 3). La puntuación de la medicación es 1 para antihistamínicos orales y / o tópicos, 2 para corticosteroides intranasales y 3 para corticosteroides orales. Las puntuaciones de los síntomas nasales se suman y se dividen por 4 para obtener una puntuación total diaria de síntomas de 0 a 3. La puntuación total diaria de medicación varía de 0 a 3. La puntuación combinada de síntomas nasales y medicación variará de 0 a 6.

E.5.1.1

Timepoint(s) of evaluation of this end point

Four weeks before randomization visit and at 6, 9 and 12 months of treatment.

Cuatro semanas antes de la visita de aleatorización y a los 6, 9 y 12 meses de tratamiento.

E.5.2

Secondary end point(s)

-Score of the nasal symptoms scale.
-Score of the specific medication scale.
-Nasal and ocular symptom scale score
-Score of the combined scale of nasal, ocular symptoms and medication.
-Percentage of days without symptoms or medication.
-VAS score (completed by the patient and the investigator) and RCAT and mini-RQLQ questionnaires.
-Specific values in serum of IgE and IgG4 specific to DPT and total DF, Der p1 and Der p2, Der p23, Der f1, Der f2 .
-Number of local and systemic reactions.
-Biochemical and hematological parameters.
-Number of days of hospitalization, number of visits to the emergency room, family doctor, specialist, ICU admission, number of absences from work / school and medication.

-Puntuación de la escala de síntomas nasales.
-Puntuación de la escala de medicación específica.
-Puntuación de la escala de síntomas nasales y oculares
-Puntuación de la escala combinada de síntomas nasales, oculares y medicación.
-Porcentaje de días sin síntomas ni medicación.
-Puntuación de la EVA (realizada por el paciente y el investigador), el cuestionario RCAT y el mini-RQLQ.
-Valores específicos en suero de IgE e IgG4 específica a DPT y DF total, Der p1 y Der p2, Der p23, Der f1, Der f2.
-Número de reacciones locales y sistémicas.
-Parámetros bioquímicos y hematológicos.
-Número de días de hospitalización, número de visitas a urgencias, médico de familia, especialista, ingreso UCI, número de ausencias laborales/escolares y medicación.

E.5.2.1

Timepoint(s) of evaluation of this end point

Symptoms and medication score will be performed four weeks before randomization visit and at 6, 9 and 12 months of treatment. The rest of the efficacy endpoints will be assessed at baseline and after 6 and 12 months of treatment. Biochemical and hematological parameters will be measured at baseline and end of the study. The rest the safety and health economics endpoints will be recorded during the whole study period.

Los síntomas y la puntuación de la medicación se realizarán cuatro semanas antes de la visita de aleatorización y a los 6, 9 y 12 meses de tratamiento. El resto de los criterios de valoración de eficacia se evaluarán al inicio del estudio y tras 6 y 12 meses de tratamiento. Los parámetros bioquímicos y hematológicos se medirán al inicio y al final del estudio. El resto de los criterios de valoración de la economía de la salud y la seguridad se registrarán durante todo el período de estudio.

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

Yes

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

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

273

F.1.3

Elderly (>=65 years)

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

350

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)

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

2021-09-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-07

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

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