Clinical Trials Register

Summary
EudraCT Number:	2016-000051-27
Sponsor's Protocol Code Number:	PM/0041
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-06-21
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

2016-000051-27

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled (DBPC) parallel-group multi-centre study to assess the efficacy and safety of PURETHAL Mites subcutaneous immunotherapy (SCIT) in patients with allergic rhinitis/rhinoconjunctivitis (ARC) caused by house dust mite (HDM) allergy

Estudio multicéntrico, aleatorizado, con doble enmascaramiento, controlado con placebo y de grupos paralelos para evaluar la eficacia y la seguridad de PURETHAL® Mites como inmunoterapia subcutánea en pacientes con rinitis/rinoconjuntivitis alérgica causada por los ácaros del polvo

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

PURETHAL Mites pivotal phIII efficacy study

Estudio pivotal de la eficacia en fase III de PURETHAL Mites

A.4.1

Sponsor's protocol code number

PM/0041

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	HAL Allergy B.V.
B.1.3.4	Country	Netherlands
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	HAL Allergy B.V.
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	HAL Allergy B.V.
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	J.H. Oortweg 15
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CH
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31881959 076
B.5.5	Fax number	+31881959 004
B.5.6	E-mail	mvnimwegen@hal-allergy.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	PURETHAL® Mites
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	A modified house dust mite extract from Dermatophagoides pteronyssinus and Dermatophagoides farinae
D.3.9.1	CAS number	8000045-20-7
D.3.9.3	Other descriptive name	ALLERGENS, HOUSE DUST & MITE
D.3.9.4	EV Substance Code	SUB12784MIG
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	50.000
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	Yes
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	Suspension 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/rhinoconjunctivitis (ARC) caused by house dust mite (HDM) allergy.

rinitis/rinoconjuntivitis alérgica (RCA) causada por los ácaros del polvo.

E.1.1.1

Medical condition in easily understood language

House dust mite (HDM) 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	19.0
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	19.0
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 clinical efficacy of 50,000 AUeq/mL (0.5 mL) PM SCIT, compared to placebo, in patients suffering from HDM-induced ARC, measured by the combined symptom and medication score (CSMS(n)) during the last 8 weeks of approximately 1 year treatment. For this primary CSMS(n) evaluation, the symptom score of the CSMS(n) will be based on nasal symptoms only.

Evaluar la eficacia clínica de 50.000 AUeq/ml (0,5 ml) de PM s.c. en comparación con el placebo en pacientes con RCA causada por los ácaros del polvo, determinada por la puntuación combinada de los síntomas y la medicación (combined symptom and medication score, CSMS(n)) durante las últimas 8 semanas de aproximadamente un año de tratamiento. Para la evaluación principal de la CSMS(n), la puntuación de los síntomas de la misma se basará únicamente en los síntomas nasales.

E.2.2

Secondary objectives of the trial

• To assess clinical efficacy of PM, compared to placebo, measured by the:
o dSS(n) (mean individual daily symptom scores, nasal symptoms only) assessed during the last 8 weeks of the approximately 1 year treatment period;
o dMS (mean daily medication score) assessed during the last 8 weeks of the approximately 1 year treatment period;
o Difference in NPT (nasal provocation test) at the end of study compared to baseline.
• To determine the onset of efficacy based on CSMS(n) for PM vs placebo.
• To compare the proportion of ‘symptom-free days’ (i.e. days without nasal symptoms) and ‘troubled days’ (i.e. days with CSMS(n) ≥ 1.5), assessed during the last 8 weeks of the approximately 1 year treatment period.
• To assess the effect of PM, compared to placebo, on Quality of Life (QoL) after approximately 1 year of treatment.
• To assess the effect of PM, compared to placebo, on serum specific immunoglobulin levels.

• Evaluar la eficacia clínica de PM, en comparación con el placebo, determinada por:
o Media individual de las puntuaciones diarias de síntomas nasales únicamente , determinada en las últimas 8 semanas de aprox un año de tto.
o Media de las puntuaciones diarias de la medicación determinada en las últimas 8 semanas de aprox 1 año de tratamiento.
o La diferencia registrada en la prueba de provocación nasal (PPN) al final del estudio respecto al valor basal.
• Determinar el inicio de la eficacia sobre la base de la CSMS(n) de PM en comparación con el placebo.
Comparar la proporción de "días sin síntomas" y de "días malos" (es decir, días con una CSMS(n) ≥ 1,5), determinada en las últimas 8 semanas de aproximadamente un año de tratamiento.
• Evaluar el efecto de PM, en comparación con el placebo, en la calidad de vida (CdV) tras aproximadamente un año de tratamiento.
• Evaluar el efecto de PM, en comparación con el placebo, en los niveles de inmunoglobulinas específicas en suero.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients who signed their informed consent form.
2. Patients aged ≥18 and ≤65 years at signing of informed consent form.
3. Patients with moderate to severe HDM-induced allergic rhinitis or rhinoconjunctivitis (based on ARIA classification) for at least one year prior to screening; with or without concomitant asthma (asthma must be controlled (GINA 2010)).
4. Patients with a history of concomitant asthma must have an FEV1 >70% of predicted value, at screening. Patients without a history of asthma must have an FEV1 >70% or a PEF >80% of predicted value at screening.
5. Patient that reported a mean CSMS(n) ≥1.5 during the baseline period .
6. Patients that are willing and capable to complete an e-diary daily during 12 weeks of the study (≥60% compliance in e-diary completion during the 14 days baseline period).
7. Patients with a positive SPT for HDM D. pter or D. far (mean wheal diameter ≥3 mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter ≥3 mm) assessed during screening or a documented positive response obtained within one year before screening.
8. Patients with an allergen specific serum IgE (ssIgE) level for HDM D. pter or D. far of ≥0.7 U/mL assessed during screening.
9. Patients with a positive NPT for HDM D. pter extract during screening (Lebel score ≥6 at 10,000 AU/mL).

1.Pacientes que hayan firmado el consentimiento informado.
2.Los pacientes que firmen el consentimiento informado han de tener edades comprendidas entre ≥18 y ≤65 años
3.Pacientes con rinitis/rinoconjuntivitis alérgica (RCA) de moderada a severa de acuerdo a la clasificación ARIA, durante al menos un año antes del screening, con o sin asma concomitante (el asma sí debe estar controlado (GINA 2010)).
4.Los pacientes con asma concomitante deben tener un FEV1<70% del valor predicho en el momento de la seleccion. Los pacientes sin historial de asma han de tener un FEV>70% o PEF>80% de los valores predichos de la seleccion.
5.Pacientes que tengan un CSMS (combined symptom and medication score) ≥1.5 durante el periodo basal.
6.Pacientes que estén dispuestos y que sean capaces de completar un diario electrónico durante las 12 semanas del estudio (con un cumplimiento ≥ 60% durante los 14 días del periodo basal).
7.Pacientes con pruebas de punción cutánea positivas para los ácaros del polvo D. pter or D. far (el diámetro medio de la roncha ≥3 mm en comparación con el control negativo; el control negativo debe ser negativo; el control de histamina debe ser positivo (diámetro medio ≥3 mm)) medido durante la selección o correctamente documentado un año antes de la seleccion.
8.Pacientes con IgEs séricas específicas para ácaros del polvo D. pter o D. far de ≥0.7 U/ml evaluado durante la selección.
9.Pacientes con una prueba de provocación nasal positiva para extractos de ácaros del polvo durante la selección (puntiación Lebel ≥6 a 10,000 AU/mL).

E.4

Principal exclusion criteria

1. Patients with concomitant sensitization i.e. positive SPT (mean wheal diameter ≥3 mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter ≥3 mm)) to other allergens than HDM, if they have expected clinically relevant symptoms related to the other allergen, overlapping with either the 8-week efficacy assessment period and/or the screening/baseline period, based on the judgement of the investigator.
2. Patients sensitized and symptomatic to pets, that will be regularly exposed to pets during the study period.
3. Patients with a history of anaphylaxis with cardio-respiratory symptoms (food allergy, drugs or an idiopathic reaction).
4. Patients who received immunotherapy (SCIT or SLIT) with HDM allergens within the past 5 years.
5. Patients with unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the past 5 years (e.g., but not limited to, prematurely stopped immunotherapy due to non-compliance, AEs, or lack of therapeutic effect).
6. Patients who undergo allergen-specific immunotherapy (SCIT or SLIT) with other allergens than HDM during the study period (screening up to EoS).
7. Patients who participated in a clinical study within the last 3 months (e.g. new investigational drug or biological) or within the last 30 days (e.g. observational study), or plans on participating in another clinical trial during the duration of this study, at the discretion of the investigator.
8. Patients that (will) receive any vaccination (including influenza vaccine) one week before start of treatment and/or during the up-dosing phase.
9. Patients undergoing any immunosuppressive treatment (e.g. anti-IgE therapy) within the last 6 months prior to inclusion and up to EoS.
10. Patients suffering from severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs.
11. Patients suffering from active malignancies or any relevant disease (see protocol for more details) .

1.Pacientes con sensibilización concomitante, p.ej. con punción cutánea positivas (diámetro de la roncha ≥3 mm comparado con el control negativo; el control negativo debe ser negativo; el control histamina debe ser positivo (diámetro de la roncha ≥3 mm)) a otros alérgenos aparte de los ácaros del polvo, en caso de que se prevean síntomas clínicamente relevantes que puedan contrapearse durante el periodo de 8 semanas al analizar la eficacia y/o durante el periodo de selección /basal a criterio del investigador.
2.Pacientes sensibilizados y sintomáticos a mascotas, que vayan a estar regularmente expuestos a mascotas durante el periodo del estudio.
3.Pacientes con un historial clínico de anafilaxis con síntomas cardio/respiratorios (alergias alimentarias, fármacos o una reacción idiopática).
4.Pacientes que hayan recibido inmunoterapia con ácaros del polvo durante los últimos 5 años.
5.Pacientes que hayan recibido inmunoterapia específica con cualquier alérgeno y que hayan fracasado, dentro de los últimos 5 años (por ejemplo, pero no limitada a, inmunoterapia detenida prematuramente debido a falta de cumplimiento, AEs o falta de efecto terapéutico) .
6.Pacientes que vayan a recibir inmunoterapia con diferentes alérgenos específicos que ácaros del polvo, durante el periodo de estudio (desde la selección hasta el fin de estudio).
7.Pacientes que hayan participado en un ensayo clínico en los últimos 3 meses (con producto en investigación o biológico) o en los últimos 30 días (en el caso de un estudio observacional), o que planifique participar en otro ensayo clínico mientras dure el presente estudio, según criterio del investigador.
8.Pacientes que vayan a recibir cualquier vacuna (incluyendo la gripe) una semana antes del inicio del tratamiento y/o durante el periodo de escalada de dosis.
9.Pacientes bajo medicación inmunosupresora (ej. Terapia anti-IgE) durante los últimos 6 meses antes de la inclusión de pacientes y hasta el fin del estudio.
10.Pacientes que sufran desórdenes inmunes severos (incluyendo los autoinmunes) y que requieran medicación inmunosupresora.
11.Pacientes que sufran desde enfermedades malignas activas o cualquier tipo de enfermedad relevante (ver protocolo para ver el listado completo).

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the Combined Symptom (nasal symptoms only) and Medication Score CSMS(n).
The primary evaluation of the CSMS(n) includes only nasal symptoms; itchy nose, sneezing, runny nose, and blocked nose (all rated from 0-3), and the medication score; 1 for oral and/or topical antihistamines, 2 for intranasal corticosteroids, and 3 for oral corticosteroids. The eye symptoms will not be taken into account in the primary evaluation, because these are less relevant for HDM induced allergies (23). The scores from the four nasal symptoms are added and divided by 4 to a total daily symptom score (dSS(n)) from 0-3. The medication score can reach a maximum of 3 and the total daily medication score ranges from 0-3. The CSMS(n) will range from 0-6.

The EAACI has recently published a position paper on the use of the CSMS as a primary end-point in allergen immunotherapy trials.

Baseline CSMS(n) will be determined during a period of 14 days during the screening period . After randomization, the e-diary will be filled out during two separate periods of 1 week (this will be skipped for patients that are suffering from any co-allergy during these periods), and during the last part of the study patients will be asked to fill in the symptom and medication e-diary on a daily basis for a period of 8 weeks. Timing of this 8 weeks period depends on the randomization date of the patients. For details on the timing of this efficacy period, please refer to the SoE (Table 1). Scores for each of these periods will be averaged. The mean CSMS(n) is the mean of the non-missing daily scores during the period considered. Patients will be asked to fill in their CSMS(n) daily on a fixed time window. For the primary endpoint the data collected during the last 8 weeks of the approximately 1 year treatment period will be used.

El criterio de valoración principal es el síntoma combinado (síntomas nasales solamente) y Puntuación de la medicaciónvCSMS (n).
La evaluación primaria de CSMS (n) incluye sólo los síntomas nasales; picazón en la nariz, estornudos, rinorrea y congestión nasal (clasificación 0-3), y la puntuación de la medicación; 1 para los antihistamínicos orales y / o tópicos, 2 de los corticosteroides intranasales, y 3 de corticosteroides orales. Los síntomas en los ojos, no se tendrán en cuenta en la primera evaluación, ya que estos son menos relevantes para las alergias inducidas por los ácaros del polvo(23). Se añaden las puntuaciones de los cuatro síntomas nasales y se dividen por 4 a una puntuación de síntomas diarios totales (DSS (n)) de 0-3. La puntuación de la medicación puede llegar a un máximo de 3 y los rangos de la puntuación del total de la medicación diaria de 0-3. Los CSMS (n) estará en el intervalo 0-6.
La EAACI ha publicado recientemente un documento de posición sobre el uso de los CSMS como principal objetivo en ensayos de inmunoterapia con alérgenos.
CSMS (n) basal se determinará durante un período de 14 días durante el período de selección. Después de la aleatorización, el diario electrónico será rellenado durante dos períodos separados de 1 semana (esto se omitirá para los pacientes que están sufriendo de cualquier co-alergia durante estos periodos), y durante la última parte del estudio se les pedirá a los pacientes que rellenen los síntoma y la medicación en el diario electrónico diariamente durante un período de 8 semanas. El momento de este período de 8 semanas depende de la fecha de aleatorización de los pacientes. Para más detalles sobre el calendario de este periodo de eficacia, por favor referirse a la Tabla 1. Será calculado las puntuaciones para cada uno de estos períodos. La media de CSMS (n) es la media de las puntuaciones diarias no perdidas durante el período considerado. Se les pedirá a los pacientes que rellenen sus CSMS (n) todos los días en un periodo de tiempo fijo. Para el criterio principal de valoración que se utilizarán los datos recogidos durante las últimas 8 semanas del periodo de tratamiento de aproximadamente 1 año.

E.5.1.1

Timepoint(s) of evaluation of this end point

Difference in mean CSMS(n) (nasal symptoms only) between PM vs. placebo treatment group, will be assessed during the last 8 weeks of the approximately 1 year treatment period.

Diferencia en la CSMS(n) media (limitada a los síntomas nasales) entre PM y el grupo del placebo determinada en las últimas 8 semanas de aproximadamente un año de tratamiento

E.5.2

Secondary end point(s)

Efficacy
• dSS(n) (nasal symptoms only), measured during the last 8 weeks of the approximately 1 year
treatment period.
• dMS measured during the last 8 weeks of the approximately 1 year treatment period.
• Difference in change from baseline in NPT outcome (Lebel score).
• Onset of efficacy based on CSMS(n), measured during the two one-week periods during treatment
and during the last 8 weeks of the approximately 1 year treatment period.
• Proportion of ‘symptom-free days’ (i.e. days without nasal symptoms) and ‘troubled days’ (i.e. days
with CSMS(n) ≥ 1.5), assessed during the last 8 weeks of the approximately 1 year treatment period.
• QoL measured with the standardized rhinoconjunctivitis quality of life questionnaire (RQLQ-S) and
EQ-5D-5L questionnaire, for all patients; and an additional asthma control questionnaire (ACQ, for
patients with concomitant asthma only) as measured during treatment (2 times) and during the last
8 weeks of the approximately 1 year treatment period.
• Difference from baseline in serum specific immunoglobulin levels (IgE, IgG, IgG4) between PM and
placebo, during and after treatment.

Safety
• Safety and tolerability assessed by:
o local and systemic reactions
o (serious) adverse events
o blood safety biochemistry/haematology parameters
o urinalysis
o vital signs
o ECG
in PM compared to placebo, as measured before, during and after treatment.

Exploratory
• Difference in CSMS (nasal and conjunctival symptoms) between PM and placebo, measured during
the last 8 weeks of the approximately 1 year treatment period.
• dSS (nasal and conjunctival symptoms), measured during the last 8 weeks of the approximately 1
year treatment period.
• Difference in aluminium levels in serum and urine in PM compared to placebo, as measured before
and after treatment.
• Difference in QoL measured with the standardized rhinoconjunctivitis quality of life questionnaire
(RQLQ-S) and EQ-5D-5L questionnaire, for all patients; and an additional asthma control
questionnaire (ACQ, for patients with concomitant asthma only) as measured two times during
treatment.
• Difference in mean CSMS(n) between PM and placebo with sufficient HDM exposure at the
patients’ home measured both at screening and at the end of the study.

Eficacia
• dSS(n) (limitada a los síntomas nasales), determinada en las últimas 8 semanas de aproximadamente un año de tratamiento.
• dMS, determinada en las últimas 8 semanas de aproximadamente un año de tratamiento.
• Diferencia en el cambio respecto del nivel basal en la PPN (en función de la escala de Lebel).
• Inicio de la eficacia en función de la CSMS(n), durante los dos periodos de tratamiento de 1 semana y durante las últimas 8 semanas de aproximadamente un año de tratamiento.
• Proporción de "días sin síntomas" (es decir, días en los que no se observen síntomas nasales) y de "días malos" (es decir, días con una CSMS(n) ≥ 1,5), determinada en las últimas 8 semanas de aproximadamente un año de tratamiento.
• CdV de todos los pacientes, determinada con el cuestionario estandarizado de calidad de vida para la rinoconjuntivitis (RQLQ-S) y el cuestionario EQ-5D-5L; y un cuestionario
Resumen del protocolo V2.1 09MAY16 Confidencial 4 de 6
EudraCT 2016-000051-27 / PM/0041 Estudio pivotal de la eficacia en fase III de PURETHAL Mites
de control del asma (ACQ, únicamente para los pacientes que sufran de asma concomitante), determinada durante el tratamiento (en dos ocasiones) y durante las últimas 8 semanas de aproximadamente un año de tratamiento.
• Diferencia en los niveles de inmunoglobulinas específicas (IgE, IgG, IgG4) en suero respecto a los niveles basales entre PM y el placebo durante y después del tratamiento.
Seguridad
• La seguridad y la tolerabilidad se evaluarán mediante:
o reacciones localizadas y sistémicas
o acontecimientos adversos (graves)
o parámetros bioquímicos y hematológicos de la seguridad en sangre
o análisis de orina
o constantes vitales
o ECG
de los pacientes tratados con PM en comparación con el placebo, antes, durante y después del tratamiento.
Exploratorios
• Diferencia en la CSMS (síntomas nasales y conjuntivales) entre PM y el placebo, determinada en las últimas 8 semanas de aproximadamente un año de tratamiento.
• dSS (síntomas nasales y conjuntivales), determinada en las últimas 8 semanas de aproximadamente un año de tratamiento.
• Diferencia en los niveles de aluminio en suero y orina de PM en comparación con el placebo, determinados antes y después del tratamiento.
• Diferencia en la CdV de todos los pacientes, determinada con el cuestionario estandarizado de calidad de vida para la rinoconjuntivitis (RQLQ-S) y el cuestionario EQ-5D-5L; y un cuestionario de control del asma (ACQ, únicamente para los pacientes que sufran de asma concomitante), determinada en dos ocasiones durante el tratamiento.
• Diferencia en la CSMS(n) media entre PM y el placebo con una exposición suficiente a ácaros del polvo en el domicilio del paciente, determinada en la selección y al final del studio.

E.5.2.1

Timepoint(s) of evaluation of this end point

Last 8 weeks of one year of treatment

Las últimas 8 semanas de aproximadamente un año de tratamiento

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

ultima visita del ultimo 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

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:

730

F.1.3

Elderly (>=65 years)

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

160

F.4.2

For a multinational trial

F.4.2.1

In the EEA

730

F.4.2.2

In the whole clinical trial

730

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)

If allowed following local country regulations, patients will receive PM (20,000 AUeq/mL) as post-study medication after completion of the study. Patients that received placebo during the study will receive 3 years, patients that received active will receive 2 years of PM therapy as post study medication.

Si se le permite seguir los reglamentos locales de cada país, los pacientes recibirán PM (20.000 AuEq / ml) como medicación post-estudio después de la finalización del estudio. Los pacientes que recibieron placebo durante el estudio recibirán 3 años, los pacientes que recibieron activo recibirán 2 años de tratamiento con PM como medicación de post-estudio.

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

2016-08-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-08-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-04-23

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