Clinical Trials Register

Summary
EudraCT Number:	2020-005823-35
Sponsor's Protocol Code Number:	20201206
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-12-09
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

Denmark - DHMA

A.2

EudraCT number

2020-005823-35

A.3

Full title of the trial

ILIT.FT – Dose finding for intralymphatic allergen immunotherapy in a randomized, parallel group, double blind placebo-controlled field trial

A.3.1

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

Effect of low dose intralymphatic immunotherapy

A.3.2

Name or abbreviated title of the trial where available

ILIT.FT

A.4.1

Sponsor's protocol code number

20201206

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	Aarhus Universitet
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Innovation Fund Denmark
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Aarhus University Hospital
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Aarhus University
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	ALK-Abelló, Hørsholm
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aarhus University, Department of Clinical Medicine
B.5.2	Functional name of contact point	Hans Jürgen Hoffmann
B.5.3	Address:
B.5.3.1	Street Address	Palle Juul Jensens Blvrd 67
B.5.3.2	Town/ city	Aarhus N
B.5.3.3	Post code	8200
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4528188147
B.5.6	E-mail	hjh@clin.au.dk
B.Sponsor: 2
B.1.1	Name of Sponsor	Aarhus Universitet
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Innovation Fund Denmark
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Aarhus University Hospital
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Aarhus University
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	ALK-Abello, Hoersholm
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aarhus Universitet
B.5.2	Functional name of contact point	Hans Jürgen Hoffmann
B.5.3	Address:
B.5.3.1	Street Address	Palle Juul Jensens Boulevard 99
B.5.3.2	Town/ city	Århus C
B.5.3.3	Post code	8200
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4528188147
B.5.6	E-mail	hjh@clin.au.dk
B.Sponsor: 3
B.1.1	Name of Sponsor	Aarhus Universitet
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Innovation Fund Denmark
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Aarhus University Hospital
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AU
B.5.2	Functional name of contact point	Hans Jürgen Hoffmann
B.5.3	Address:
B.5.3.1	Street Address	Palle Juul Jensens Blvrd 67
B.5.3.2	Town/ city	Aarhus N
B.5.3.3	Post code	8200
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4528188147
B.5.6	E-mail	hjh@clin.au.dk
B.Sponsor: 4
B.1.1	Name of Sponsor	Aarhus Universitet
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Innovation Fund Denmark
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Aarhus University Hospital
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	Aarhus University
B.4.2	Country	Denmark
B.4.1	Name of organisation providing support	ALK-Abelló
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aarhus University, Department of Clinical Medicine
B.5.2	Functional name of contact point	Hans Jürgen Hoffmann
B.5.3	Address:
B.5.3.1	Street Address	Palle Juul Jensens Boulevard 99
B.5.3.2	Town/ city	Århus N
B.5.3.3	Post code	8200
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4528188147
B.5.5	Fax number	28188147
B.5.6	E-mail	hjh@clin.au.dk

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	Alutard SQ phleum pratense (ALK 225)
D.2.1.1.2	Name of the Marketing Authorisation holder	ALK-Abelló
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Alutard SQ phleum pratense (ALK 225)
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	Intralymphatic use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	PHLEUM PRATENSE (225)
D.3.9.4	EV Substance Code	SUB123113
D.3.10	Strength
D.3.10.1	Concentration unit	SQU Standardised Quality Unit(s) (Deprecated)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	100 to 300
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

Allergic rhinitis

E.1.1.1

Medical condition in easily understood language

hayfever

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10039085
E.1.2	Term	Rhinitis allergic
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10010744
E.1.2	Term	Conjunctivitis allergic
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary aim of the trial is to test the hypothesis that there is similar or more efficacy associated with fewer side effects of intralymphatic immunotherapy with 300 SQ-U/injection than with 1000 SQ-U/injection.

E.2.2

Secondary objectives of the trial

2.1 change in specific IgE to Grass and Phl p5 with ImmunoCAP, and of grass molecules on the ISAC chip with different treatment intensities
2.2.1 Improvement in cSMS expressed as but also as mild (Well) days and severe (Hell) days , which is more patient oriented, and as response to Log10 of daily grass pollen counts.
2.2.2 We will test the predictive ability of the skin prick test as a ratio of the histamine positive control (Cha) for cSMS
2.2.3 Effect of treatment arms on the well standardised Junipers RQLQ on a weekly basis during the grass pollen season 2021.
3. Safety assessment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients have seasonal grass pollen induced rhino conjunctivitis during the two most recent seasons and a positive skin prick test resulting in a wheal diameter ≥ 3 mm to ALK Soluprick Grass 225. The latter is important as it predicts that the patients IgE recognises allergens found in ALKs preparation for treatment, a crucial condition for treatment success.
Patients are adults; more than 18 years old on the day of first treatment,
Patients must be comfortable with digital data entry and have accepted and digitally approved the informed consent document.
Patient have to have sufficient symptoms during the grass pollen season to allow us to record an effect of the treatment; we will evaluate question 1 – 6 and 18 – 22 of their RHINE III and the sum of the retrospective RTSS questionnaires from the pre-screening tools to assess the severity of grass pollen dependent rhinoconjunctivitis and to identify or predict possible grass pollen dependent asthma affecting patients. For inclusion, patients have to have a retrospective RTSS score >7 on a scale of 0 – 18 (most severe). We will select patients with the highest RTSS score.
90% of patients included for the baseline year will be included in the treatment study.

E.4

Principal exclusion criteria

pregnancy
1 previous allergen immunotherapy for grass pollen allergy
2 Significant allergic sensitisation to mugwort (Artemisia vulgaris) or sensitisation with persistent exposure to pet animal allergens that results in allergic symptoms
3 Known or suspected allergy to additives to the study product; allergy to aluminium hydroxide or phenol
4 Depot steroid injection for treatment of allergic rhinoconjunctivitis
5 Upper airway disease (non-allergic sinusitis, nasal polyps)
6 uncontrolled asthma or severe asthma with post bronchodilator FEV1<70% of expected, decided by the investigator
7 Pulmonary disease, perennial or seasonal with daily use of more than 800 microgram inhaled budesonide/ day (or equivalent) or treatment with omalizumab or other biologics for allergy or asthma.
8 Pulmonary disease with post bronchodilator FEV1 < 70 % of predicted
9 Allergic reaction within the last 4 days or anaphylaxis last month before ILIT injections

10 severe Autoimmune or collagen disease
11 Disease or conditions rendering the treatment of anaphylactic reactions difficult (symptomatic coronary heart diseases, severe arterial hypertension and treatment with beta-blockers)
12 Known cardiovascular disease, i.e. not even NYHA class I.
13 Use of ACE-blockers. If ACE-blockers are used, they should be withdrawn after discussion with the Principal Investigator 2 weeks before first injection and until after the last injection
14 Recent or on-going hepatic or renal disease
15 All malignant diseases
16 Immuno- or chemotherapy during the last 15 years,
17 Increased bleeding tendency
18 Any other than study medication with an effect of interfering with the immune response
19 Chronic obstructive or restrictive lung disease
20 Skin diseases with barrier defect in the inguinal areas
21 Alcohol or drug abuse
22 Participation in another clinical study from visit 1-8.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is a comparable or better reduction in median cSMS due to treatment with 300 SQ-U Allergen compared with patients treated with 1000 SQ-u during the grass pollen season of 2021

E.5.1.1

Timepoint(s) of evaluation of this end point

Change in parameters between groups in the grass pollen season after treatment.

E.5.2

Secondary end point(s)

Change in skin prick test from before treatment (Spring 2021) to after the first season after treatment (Autumn 2021) in the group treated with 300 SQ-U is similar or better than in the group treated with 1000 SQ-U.
Change in Junipers RQLQ in the group treated with 300 SQ-U is similar or better than in the group treated with 1000 SQ-U.
Change in IgE and IgG4 is similar or better in the group treated with 300 SQ-U is similar or better than in the group treated with 1000 SQ-U

E.5.2.1

Timepoint(s) of evaluation of this end point

Change in skin prick test before treatment to after the season after treatment.
Change in other parameters between groups in the grass pollen season after treatment, as well as in the second season after treatment.

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

lower dose of Alutard - comparing 1000 and 300 SQ-U

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

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:

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

Yes

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.4.2.2

In the whole clinical trial

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

2021-01-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-01-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-02-28

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