Clinical Trials Register

Summary
EudraCT Number:	2020-004328-41
Sponsor's Protocol Code Number:	AL0001nh
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-04-13
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

Germany - PEI

A.2

EudraCT number

2020-004328-41

A.3

Full title of the trial

A multicentre, randomized, open label clinical trial for the safety evaluation of a short dose escalation scheme using one strength for allergen immunotherapy with an aluminium-hydroxide adsorbed native allergen preparation of house dust mite allergens in adult and adolescent patients with moderate to severe allergic rhinitis or rhinoconjunctivitis with or without asthma.

Eine multizentrische, randomisierte, offene klinische Prüfung zur Untersuchung der Verträglichkeit eines verkürzten Aufdosierungsschemas für ein Einstärken-Präparat zur spezifischen Immuntherapie mit einem Aluminium-hydroxid adsorbierten nativen Hausstaubmilben Allergenpräparat bei Erwachsenen und Jugendlichen mit mittelschwerer bis schwerer allergischer Rhinitis oder Rhimokonjunktivitis mit oder ohne Asthma.

A.3.1

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

Study to investigate the safety of a short (fast) dose escalation in immune therapy with house dust mite allergens as compared to the approved long (slow) dose escalation in adult and adolescent patients with allergic cold (with and w/o asthma).

Studie zur Untersuchung der Sicherheit einer kurzen (schnellen) Dosiseskalation in der Immuntherapie mit Hausstaubmilbenallergenen im Vergleich zu der zugelassenen langen (langsamen) Dosiseskalation bei erwachsenen und jugendlichen Patienten mit allergischem Schnupfen (mit und ohne Asthma).

A.3.2

Name or abbreviated title of the trial where available

TiME (short allergen immunotherapy mites)

A.4.1

Sponsor's protocol code number

AL0001nh

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	Allergopharma GmbH & Co. KG
B.1.3.4	Country	Germany
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	Allergopharma GmbH & Co. KG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Allergopharma GmbH & Co. KG
B.5.2	Functional name of contact point	Clinical Project Leader
B.5.3	Address:
B.5.3.1	Street Address	Hermann-Körner-Straße 52
B.5.3.2	Town/ city	Reinbek
B.5.3.3	Post code	21465
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4940727650
B.5.5	Fax number	+494072765600
B.5.6	E-mail	kristina.duwensee@allergopharma.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	Novo-Helisen Depot house dust 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.3.9.1	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	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5000
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	Comparator
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	NOVO-HELISEN® DEPOT
D.2.1.1.2	Name of the Marketing Authorisation holder	Allergopharma GmbH & Co. KG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	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.3.9.1	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	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	50 to 5000
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

moderate to severe allergic rhinitis or rhinoconjunctivitis with or without asthma

E.1.1.1

Medical condition in easily understood language

moderate to severe allergic cold with or without asthma

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	10001723
E.1.2	Term	Allergic rhinitis
E.1.2	System Organ Class	100000004855

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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

to evaluate the safety and tolerability of an accelerated high dose escalation scheme with one strength for allergen immunotherapy with NHD D.p./D.f. 50%/50% compared to the standard escalation scheme involving 3 strengths in adults and adolescents with rhinitis or rhinoconjunctivitis caused by house dust mite allergens with or without allergic asthma

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent given from patient (and parents/legal guardian(s), as applicable)

2. Age between 12 and ≤ 65 years

3. IgE-mediated moderate to severe allergic rhinitis or rhinoconjunctivitis with or without allergic asthma caused by house dust mite allergens (established and documented as part of the screening procedures)

4. Symptoms of allergic rhinitis or rhinoconjunctivitis triggered by house dust mite exposure over at least the last 2 years

5. No diagnosis of bronchial asthma in medical history, or confirmed diagnosis of asthma as being “well controlled”

6. Previous symptomatic anti-allergic treatment for at least 2 years prior to enrolment

7. Negative SARS-CoV-2 test result

E.4

Principal exclusion criteria

General criteria:
1. Patients and if relevant parents/legal guardian(s) are unable to understand and comply with the requirements of the trial, as judged by the investigator
2. Currently participating in another clinical trial or participating in any other clinical trial within 30 days prior informed consent for this trial
3. Low adherence to trial procedures expected or inability to understand instructions/trial documents by participant and/or parents/legal guardian(s)
4. Involvement in the planning and conduct of the trial
5. Patients and if relevant parent/legal guardian is employee of Allergopharma GmbH & Co. KG or of one of the trial sites or CRO
6. Any relationship of dependence with the sponsor or with the investigator
7. Previous randomization to treatment in the present trial
8. Mentally disabled
9. Institutionalized due to an official or judicial order

For female patients with childbearing potential
10. Positive urine pregnancy test or pregnant
11. Wish to become pregnant during the course of the trial
12.Not using highly effective and reliable contraception, as judged by the investigator (reliable and highly effective methods of birth control defined as failure rate less than 1% per year)
13. Wish to breast feed or breast feeding

Immunotherapy criteria:
14. History of a confirmed anaphylaxis after an AIT injection
15. AIT with house dust mite allergoids or allergens within the last 5 years
16. Current treatment with any kind of allergen immunotherapy (AIT)
17. AIT with unknown allergen within the last 5 years Diseases and health status:
18. Clinically relevant chronic rhinoconjunctival or respiratory symptoms related to other reasons than allergy
19. Forced expiratory volume in 1 second (FEV1) < 70 % of predicted normal values according to Quanjer (Quanjer et al. 2012) under adequate asthma treatment according to
GINA recommendation (GINA 2020)
20. Uncontrolled or partly controlled asthma according to GINA recommendation (INA 2020)
21. Acute asthma attack within the last 6 months prior to randomization defined as unscheduled doctors visit, hospitalization, or emergency visit
22. Severe acute or chronic diseases (e.g. COVID-19, chronic urticaria, mastocytose, active tuberculosis, diabetes mellitus type I, malignant neoplasia, chronic renal failure), severe inflammatory diseases (liver, kidneys), acute viral and bacterial infections presenting with fever
23. Autoimmune diseases, immune defects including immunosuppression, immune-complexinduced immunopathies (e.g. HIV, post-transplant patients, lupus erythematodes [SLE], vitiligo, Grave’s disease, multiple sclerosis)
24. Severe psychiatric and psychological disorders including impairment of cooperation (e.g. alcohol or drug abuse)
25. Recurrent seizures (e.g. febrile convulsion, untreated epilepsy)
26. Irreversible secondary alterations of the reactive organ (e.g. emphysema, bronchiectasis)
27. For assessment the normal reference ranges of the central laboratory should be applied. If out of range, laboratory values greater than grade 1 according to the FDA Guidance for Industry (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) will lead to exclusion of the patient.

Medications:
28. Use of β-blockers (locally or systemically), ACE inhibitors
29. Contraindication for use of adrenalin (e.g. acute or chronic symptomatic coronary heartdisease, severe hypertension)
30. Completion or ongoing treatment with anti-IgE-antibodies (e.g. omalizumab)
31. Hypersensitivity to excipients of the investigational medical product Novo-Helisen Depot house dust mite preparation

E.5 End points

E.5.1

Primary end point(s)

(descriptive safety variables)
1) Number, incidence, time of onset, type and intensity of AEs and serious adverse events (SAE) according to MedDRA primary system organ class (SOC) and preferred term
2) Number, incidence, time of onset, type and intensity of AEs and serious adverse events assessed as drug related (by investigator) according to MedDRA primary SOC and preferred term
3) Incidence and intensity of allergic systemic reactions after injections according to the World Allergy Organization (WAO) grading system
4) Number of patients reaching the maintenance dose without dose adjustment due to adverse events
5) Change of laboratory values (hematology, clinical chemistry and urinalysis) measured before and after the treatment phase
6) Change of vital signs and lung function measured before and after the treatment phase
7) Assessment of the overall tolerability by the investigator and the patient using a 5 point Likert scale (Likert 1932)

E.5.1.1

Timepoint(s) of evaluation of this end point

endpoints 1, 2, 3:
cumulative data from every visit except screening visit 1:
for accelerated dose escalation group (G1): screening phone contact (week -2 - 0), weeks 0, 1, 2, 3, 4, 5, 7, 11, follow-up visit (week 13 - 15)
for standard dose escalation group (G2): screening phone contact (week -2 - 0), weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 8, 10, 11, 12, 13, 15, 19, follow-up visit (week 21 - 23)

endpoint 4:
for G1: week 5
for G2: 13

endpoints 5, 6:
screening visit 1, follow-up visit (G1: week 13 - 15; G2: week 21 - 23)

endpoint 7:
for G1: weeks 1, 2, 3, 4, 5, 7, 11, follow-up visit (week 13 - 15)
for G2: weeks 1, 2, 3, 4, 5, 6, 7, 8, 8, 10, 11, 12, 13, 15, 19, follow-up visit (week 21 - 23)

E.5.2

Secondary end point(s)

exploratory enpoint:
IgG4 specific for Dermatophagoides farinae and Dermatophagoides pteronyssinus

E.5.2.1

Timepoint(s) of evaluation of this end point

Screening visit (week -14 - 0), follow-up visit (group 1: week 13 - 15; group 2: week 21 - 23)

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

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

Yes

E.6.13.1

Other scope of the trial description

tolerability

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

Yes

E.8.2.2

Placebo

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

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

database lock

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

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:

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

140

F.4.2.2

In the whole clinical trial

140

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-04-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-04

P. End of Trial
P.	End of Trial Status	Completed

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