Clinical Trials Register

Summary
EudraCT Number:	2018-004262-34
Sponsor's Protocol Code Number:	MM09-SIT-023
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:	2020-01-14
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

2018-004262-34

A.3

Full title of the trial

Randomized, placebo-controlled, prospective clinical trial of efficacy and safety for the treatment of rhinitis/rhinoconjunctivitis and asthma against a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae allergen extract

Ensayo clínico prospectivo aleatorizado controlado con placebo de eficacia y seguridad para el tratamiento de rinitis/rinoconjuntivitis y asma por alergia frente a un extracto alergénico con mezcla de Dermatophagoides pteronyssinus and Dermatophagoides farinae

A.3.1

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

A.4.1

Sponsor's protocol code number

MM09-SIT-023

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	Inmunotek, S.L.
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	INMUNOTEK, S.L.
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	INMUNOTEK, S.L.
B.5.2	Functional name of contact point	Miguel Casanovas
B.5.3	Address:
B.5.3.1	Street Address	Punto Mobi, 5
B.5.3.2	Town/ city	Alcalá de Henares
B.5.3.3	Post code	28805
B.5.3.4	Country	Spain
B.5.4	Telephone number	34912908942110
B.5.5	Fax number	34916639732
B.5.6	E-mail	mcasanovas@inmunotek.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	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	MM09-I
D.3.4	Pharmaceutical form	Solution 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	N/A
D.3.9.2	Current sponsor code	MM09-I
D.3.9.3	Other descriptive name	HOUSE DUST MITE ALLERGEN EXTRACT
D.3.9.4	EV Substance Code	SUB50983
D.3.10	Strength
D.3.10.1	Concentration unit	AU/ml allergy unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10.000
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.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	MM09-II
D.3.4	Pharmaceutical form	Solution 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	N/A
D.3.9.2	Current sponsor code	MM09-II
D.3.9.3	Other descriptive name	HOUSE DUST MITE ALLERGEN EXTRACT
D.3.9.4	EV Substance Code	SUB50983
D.3.10	Strength
D.3.10.1	Concentration unit	AU/ml allergy unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30.000
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

House dust mites allergy

Alergia frente a los ácaros Dermatophagoides pteronyssinus y Dermatophagoides farinae

E.1.1.1

Medical condition in easily understood language

House dust mites allergy

Alergia frente a los ácaros Dermatophagoides pteronyssinus y Dermatophagoides farinae

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10020419
E.1.2	Term	House dust mite allergy
E.1.2	System Organ Class	100000004870

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10001728
E.1.2	Term	Allergic rhinoconjunctivitis
E.1.2	System Organ Class	100000004853

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	10034382
E.1.2	Term	Perennial allergic rhinitis
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 clinical efficacy of polymerized allergenic extracts, administered subcutaneously, compared to placebo in subjects with moderate to severe persistent/ intermittent rhinoconjunctivitis associated with mild to severe persistent/intermittent asthma in mites sensitized subjects, without sensitization to other pneumoallergens, by combining the symptoms and the consumption of the medicine necessary for the control of asthma with rhinitis / rhinoconjunctivitis.

El objetivo principal de este ensayo es evaluar la eficacia clínica de los extractos alergénicos polimerizados, administrados por vía subcutánea, comparado con placebo en sujetos con rinoconjuntivitis persistente moderada – grave asociado a asma persistente leve-moderada controlada y que se encuentren sensibilizados a ácaros, sin sensibilización a otros neumoalergenos, mediante la puntuación combinada de síntomas y de consumo de medicación necesaria para el control del asma con rinitis/rinoconjuntivitis.

E.2.2

Secondary objectives of the trial

As secondary objectives will be assessed the tolerance, changes in immunological parameters, the subject quality of life, after the treatment and the safety of the subcutaneous immunotherapy

Como objetivos secundarios se evaluarán la tolerancia, cambios en parámetros inmunológicos, la calidad de vida del sujeto tras el tratamiento y la seguridad de la inmunoterapia subcutánea

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Written informed consent
- Positive suggestive clinical history of inhalation allergy (moderate-severe persistent/ rhinitis/ rhinoconjunctivitis with mild-moderate controlled persistent asthma) due to Dermatophagoides pteronyssinus and / or Dermatophagoides farinae allergy
- Subjects with a positive prick test (wheal size > 5 mm)
- Specific immunoglobulin E against house mites (Dermatophagoides pteronyssinus and/or Dermatophagoides farinae) > 10 kU/L (Class 3) and whose determinations does not exceed 6 months prior to the inclusion visit
- Subjects that are not sensitized to environmental allergens from other groups (pollens, mushrooms, animal epithelia, food, medicines or poisons).
- Subjects with diagnosis of asthmatic pathology performed by bronchodilator test or patients with previous diagnosis of asthma by clinical history
- Age between 14 and 65 years
- Both genders
- Subjects capable of complying with the study protocol
- Subjects who have not received immunotherapy in the last 5 years

- Sujeto que haya firmado el consentimiento informado
- Sujetos con historia clínica confirmada de alergia inhalatoria (rinitis y/o rinoconjuntivitis persistente moderada-grave con asma persistente controlada leve-moderada) causada por alergia a Dermatophagoides pteronyssinus y/o Dermatophagoides farinae
- Sujetos con un prick-test positivo (diámetro medio de la pápula de 5 mm) frente a un extracto de Dermatophagoides pteronyssinus y/o Dermatophagoides farinae
- IgE específica (CAP) frente a ácaros (Dermatophagoides pteronyssinus y/o Dermatophagoides farinae) con un valor > 10 KU/L (Clase 3) y cuya determinación no supere los 6 meses anteriores a la visita de inclusión
- Sujetos que no estén sensibilizados a alérgenos ambientales de otros grupos (polenes, hongos ni epitelios de animales), alimentos, medicamentos o venenos.
- Pacientes con diagnóstico de patología asmática realizado mediante test de broncodilatadores o pacentes diagnóstico previo de asma por historia clínica
- Sujetos con edad comprendida entre 14 y 65 años
- Ambos sexos
- Sujetos capaces de otorgar el consentimiento informado
- Sujetos capaces de cumplir con el protocolo del estudio
- Sujetos que no hayan recibido inmunoterapia frente a ácaros en los últimos 5 años

E.4

Principal exclusion criteria

- Subjects who have not given written informed consent
- Subjects outside of the age range
- Subjects who have previously received immunotherapy for the treatment of the allergic rhinoconjunctivitis and asthma in the last 5 years., or a cross-reactive allergen or are currently receiving immunotherapy with any allergen
-Subjects that immunotherapy can be subject to absolute general contraindication according to the criteria of the Immunotherapy Committee of the Spanish Society of Allergy and Clinical Immunology and of the European Allergy and Clinical Immunology Immunotherapy Subcommittee
- Subjects with intermittent or severe persistent or uncontrolled asthma, with a FEV1<60% with respect to the reference value despite the appropiate pharmacological treatment at the time of inclusion in the trial. Also subjects with intermittent rhinitis or with moderate to severe symptoms in whom the suspension of the systemic antihistamine treatment is contraindicated
-- Subjects who have required oral corticosteroids in the 12 weeks previous to the inclusion in the trial
- Subjects who have previously suffered a serious secondary reaction during the skin prick test
-Subjects in treatment with beta blockers
-Unstable subjects from the clinical point of view at the time of the inclusion in the trial (acute asthmatic exacerbation, respiratory infection, febrile, acute urticaria, etc.)
-Subjects with chronic urticaria, severe dermographism, severe atopic dermatitis, sunburn, active psoriasis with lesions in areas where skin tests will be performed, or a history of hereditary angioedema
-Subjects with some pathology in which the administration of adrenaline is contraindicated (hyperthyroidism, hypertension, heart disease, etc.)
-Subjects with any other disease not associated with the moderate rhinoconjunctivitis or asthma, but of potential severity and that could interfere with the treatment and follow-up (epilepsy, psychomotor deterioration, diabetes, malformations, multi-operated, kidney diseases,…).
-Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumor diseases or with a diagnosis of immunodeficiency
-Subject whose status prevents him from providing cooperation and/or who presents severe psychiatric disorders
-Subjects with known allergy to other vaccine components different from mite allergen extract
-Subjects with lower airway diseases other than asthma such as emphysema or bronchiectasis
-Direct investigator’s relatives
-Pregnant or women at risk of pregnancy women

- Sujetos que no hayan otorgado el consentimiento informado por escrito.
- Sujetos fuera del rango de edad.
- Sujetos que hayan recibido previamente inmunoterapia para el tratamiento de la rinoconjuntivitis y asma alérgica por ácaros en los 5 años previos. Tampoco podrán incluirse los pacientes en los que la inmunoterapia pueda ser objeto de contraindicación general absoluta según los criterios del Comité de Inmunoterapia de la Sociedad Española de Alergia e Inmunología Clínica y del European Allergy and Clinical Immunology Immunotherapy Subcommittee ).
- Sujetos con asma intermitente o persistente grave o no controlada, con un FEV1 < 60% con respecto al valor de referencia a pesar de un tratamiento farmacológico adecuado en el momento de la inclusión en el ensayo. Así mismos sujetos con rinitis intermitente o con síntomas moderados a severos en los cuales la suspensión del tratamiento anthistamínicos por vía sistémica sea contraindicado
- Sujetos que hayan requerido corticoides orales en las 12 semanas previas al momento de la inclusión en el ensayo
- Sujetos que hayan presentado previamente una reacción secundaria grave durante la realización de pruebas cutáneas de diagnóstico mediante prick test
- Sujetos en tratamiento con ß-bloqueantes.
- Sujetos inestables desde el punto de vista clínico en el momento de la inclusión en el ensayo (exacerbación asmática aguda, infección respiratoria, proceso febril, urticaria aguda, etc.).
- Sujetos con urticaria crónica activa, dermografismo severo, dermatitis atópica severa, quemaduras solares, psoriasis activa con lesiones en zonas donde se realizarán pruebas cutáneas, o antecedentes de angioedema hereditario.
- Sujetos que tengan alguna patología en la que esté contraindicada la administración de adrenalina (hipertiroidismo, HTA, cardiopatía, etc.).
- Sujetos con alguna otra enfermedad no relacionada con la rinoconjuntivitis moderada o con el asma, pero de potencial gravedad y que pueda interferir con el tratamiento y seguimiento (epilepsia, alteración psicomotora, diabetes, malformaciones, multioperados, nefropatías,).
- Sujetos con enfermedad autoinmune (tiroiditis, lupus, etc.), enfermedades tumorales o con diagnóstico de inmunodeficiencias.
- Sujeto cuyo estado le impide ofrecer cooperación y o que presente trastornos psiquiátricos severos.
- Sujetos con alergia conocida a otros componentes de la vacuna diferentes del alérgeno.
- Sujetos con enfermedades de la vía respiratoria inferior diferentes al asma como el enfisema o las bronquiectasias.
- Sujetos que sean familiares directos de los investigadores.
- Mujeres embarazadas. Las mujeres fértiles deberán acceder a usar un método anticonceptivo médicamente aceptable. Una mujer fértil se define como una mujer que es biológicamente capaz de quedarse embarazada. Los métodos anticonceptivos médicamente aceptables son dispositivos intrauterinos colocados con, al menos, 3 meses de antelación, la esterilización quirúrgica (por ejemplo, ligaduras de trompas), métodos de barrera o el uso de anticonceptivos orales”.

E.5 End points

E.5.1

Primary end point(s)

Combined symptom and medication score at the beginning and the end of the trial that will be evaluated by the symptom diary.

Puntuación combinada de síntomas y consumo de medicación concomitante entre el inicio y el final del ensayo que se evaluaran mediante el diario de síntomas.

E.5.1.1

Timepoint(s) of evaluation of this end point

Begining and end of the clinical trial

Principio y final del ensayo

E.5.2

Secondary end point(s)

- Skin prick test
- Free days of symptoms and medication
- Asthmatic Exacerbations (Number, severity and time)
- Quality of life
- Visual analogue scales
- Immunological parameters: total and specific IgE; IgG (specific IgG4)
- Registration of health consumption
- Safety variables

- Prick test diagnóstico
- Días libres de síntomas y medicación
- Exacerbaciones asmáticas (Número, severidad y tiempo)
- Calidad de vida medida en cuestionarios (ESPRINT 15, ACT)
- Escala visual analógica (EVA)
- Parámetros inmunológicos IgE total y específica, IgG (IgG4 específica)
- Registro de consumo sanitario
- Variables de seguridad

E.5.2.1

Timepoint(s) of evaluation of this end point

Begining and end of the clinical trial

Principio y final del ensayo

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Nada

None

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

The trial will finished with the database closed out.

El ensayo finalizará con el cierre de la base de datos de los resultados del ensayo.

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:

100

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

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

150

F.4.2

For a multinational trial

F.4.2.1

In the EEA

150

F.4.2.2

In the whole clinical trial

150

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

2020-04-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-24

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

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