Clinical Trials Register

Summary
EudraCT Number:	2019-002847-62
Sponsor's Protocol Code Number:	TCS_19_02
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-11-21
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

Austria - BASG

A.2

EudraCT number

2019-002847-62

A.3

Full title of the trial

Clinical evaluation of two different dosage groups of Tacrosolv over 8 days with once daily administration in a placebo controlled cross-over design to evaluate safety and efficacy in patients suffering from grass pollen-induced allergic rhinoconjunctivitis in the Vienna Challenge Chamber.

Klinische Bewertung von zwei verschiedenen Dosierungsgruppen von Tacrosolv über 8 Tage mit einmal täglicher Verabreichung in einem Placebo kontrollierten Crossover-Design zur Bewertung der Sicherheit und Wirksamkeit bei Patienten mit Gräserpollen induzierter allergischer Rhinokonjunktivitis unter Verwendung der Vienna Challenge Chamber.

A.3.1

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

Clinical study to evaluate safety and efficacy of two different dosage groups of Tacrosolv eye drops in patients suffering from grass pollen-induced allergic rhinoconjunctivitis.

Klinische Studie zur Wirksamkeit und Sicherheit zweier unterschiedlicher Dosen von Tacrosolv Augentropfen in allergischen Patienten mit graspolleninduzierbarer Bindehautentzündung.

A.4.1

Sponsor's protocol code number

TCS_19_02

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	Marinomed Biotech AG
B.1.3.4	Country	Austria
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	Marinomed Biotech AG
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Marinomed Biotech AG
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Veterinaerplatz 1
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1210
B.5.3.4	Country	Austria
B.5.4	Telephone number	+431250774460
B.5.5	Fax number	+431250774493
B.5.6	E-mail	cornelia.siegl@marinomed.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	Tacrosolv 50 micrograms, eye drops
D.3.2	Product code	Tacrosolv
D.3.4	Pharmaceutical form	Ear/eye drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Conjunctival use (Noncurrent) Topical use (Noncurrent) Ophthalmic use (Noncurrent) Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tacrolimus
D.3.9.1	CAS number	109581-93-3
D.3.9.2	Current sponsor code	n.a.
D.3.9.3	Other descriptive name	TACROLIMUS MONOHYDRATE
D.3.9.4	EV Substance Code	SUB23141
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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)	No
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	Ear/eye drops, solution
D.8.4	Route of administration of the placebo	Ophthalmic use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Allergic rhinoconjunctivitis

E.1.1.1

Medical condition in easily understood language

Allergic red eye

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

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	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

The primary objective of the trial is to demonstrate the safety and efficacy of two doses of Tacrosolv (1 drop per eye per day - low dose treatment; 2 drops per eye per day - high dose treatment) on day 8 of treatment.

E.2.2

Secondary objectives of the trial

Secondary objective of the trial is to evaluate the onset of action of either dose of Tacrosolv on day one of treatment as well as efficacy differences between low dose and high dose treatment on day eight.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

I1. Written informed consent obtained before any trial related procedures are performed
I2. Healthy male or female subjects aged 18 to 65 years
I3. Female subjects of child-bearing potential must have a negative pregnancy test and be willing to practice appropriate and safe contraceptive methods until the end of treatment visit
I4. A documented clinically relevant allergic history of moderate to severe SAR with rhinoconjunctivitis to grass pollen for the previous two years
I5. Subjects exhibit a moderate to severe response to approximately 1800 grass pollen grains/m3 within the first 2 hours in the Vienna Challenge Chamber, which is defined as total ocular symptom score (TOSS) of at least 4 (out of 12) with at least one single ocular symptom scored ≥2 (“moderate”) at least twice during the first two hours of the screening challenge session using standard VCC grass pollen allergen mixture. Ocular symptom score is the sum of “ocular redness”, “ocular itching”, “watery eyes”, ”gritty feeling” each of which have been scored on a categorical scale from 0 to 3.
I6. Positive Skin Prick Test (SPT) response (wheal diameter at least 3 mm larger than diluent control) to grass pollen SPT solutions (standard Allergopharma) at screening or within the last 12 months prior to study start.
I7. Positive serum specific IgE against recombinant major allergen components of the used grass pollen e.g. g6 (specific CAP IgE ≥0.70 kU/L) at screening or within the last 12 months prior to study start.
I8. Non-smoking subjects (smoked <10 packs per year in their lifetime and had not smoked in the last 6 months).
I9. Asthma patients only if the asthma condition is mild or intermittent, and if those are not treated with steroids
I10. Subject has a forced expiratory volume in 1 second (FEV1) of at least 80% of predicted value (ECCS) at the screening.
I11. Subject is capable of understanding the study procedures and potential risks associated with the study, and voluntarily agrees to participate by giving written informed consent.
I12. Subject is able to adhere to dose and visit schedules.
I13. Subject is able to read, understand and complete questionnaires and diaries.

E.4

Principal exclusion criteria

E1 Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted and safe birth control method (pregnancy to be controlled by a pregnancy dipstick test).
E2 Contact lens users
E3 A clinical history of uncontrolled asthma within 3 months prior to screening.
E4 Subjects with asthma requiring treatment with inhaled or oral corticosteroids on a regular basis judged by the investigator.
E5 Previous successful immunotherapy to grass pollen, a grass pollen allergen or a cross-reacting allergen within the past 3 years
E6 Ongoing treatment with any allergen-specific immunotherapy product
E7 Subjects with a current oral candidiasis infection or treatment for oral candidiasis during the last 30 days before starting the study.
E8 Subjects with history of tuberculosis.
A subject meeting any of the exclusion criteria listed below must be excluded from participating in the trial:

E1 Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted and safe birth control method (pregnancy to be controlled by a pregnancy dipstick test).
E2 Contact lens users
E3 A clinical history of uncontrolled asthma within 3 months prior to screening.
E4 Subjects with asthma requiring treatment with inhaled or oral corticosteroids on a regular basis judged by the investigator.
E5 Previous successful immunotherapy to grass pollen, a grass pollen allergen or a cross-reacting allergen within the past 3 years
E6 Ongoing treatment with any allergen-specific immunotherapy product
E7 Subjects with a current oral candidiasis infection or treatment for oral candidiasis during the last 30 days before starting the study.
E8 Subjects with history of tuberculosis.
E9 Subjects with any fungal/viral/bacterial respiratory or systemic infections during the last 30 days.
E10 Symptoms of or treatment for upper respiratory tract infection, acute sinusitis, acute otitis media or other relevant infectious process (at randomization)
E11 Subjects with uveitis, prior chemical burn to the ocular surface, pemphigoid, Mooren’s ulcer, ulcerative keratitis, bacterial/fungal/viral infection of the eye
E12 Subjects using any ophthalmic steroids during the last 30 days
E13 Subjects treated with nasal, inhaled or systemic immunosuppressants during the last 30 days
E14 History of anaphylaxis with cardiorespiratory symptoms (immunotherapy, exercise induced, food allergy, drugs or an idiopathic reaction).
E15 Any clinically relevant chronic disease judged by the investigator.
E16 Systemic or ocular disease involving the immune system judged by the investigator.
E17 Use of an investigational drug within 30 days/5 half-lives of the drug (which ever longest) prior to screening.
E18 History of allergy, hypersensitivity or intolerance to any ingredients of the IMP.
E19 History of alcohol or drug abuse.
E20 Being immediate family of the investigator or trial staff, defined as the investigator's/staff’s spouse, parent, child, grandparent or grandchild.
E21 Subjects treated with topical anti-allergy or cyclosporin-containing eyedrops within 2 weeks before study start.
E22 Subjects treated with leukotriene antagonists (1 month before study start), long- lasting anti-histamines, like cetirizine, fexofenadine, loratadine, desloratadine, hydroxyzine (5 to 10 days before study start), mast cell stabilizer (2 weeks before study start) or nasal decongestant (3 days before study start).
E23 Subjects with hypersensitivity to immunosuppressants judged by the investigator.
E24 Presence or history of any ocular infection or clinically significant inflammation
E25 Ocular surgery in the 3 months preceding the study
E26 Treatment with corticosteroids in the 4 weeks preceding the study
E27 Is currently being treated with a medication that induces or inhibits CYP3A4 or 5

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint will be the mean 'Total Ocular Symptom Score' (TOSS), calculated as the baseline adjusted mean of TOSS measured every 15 minutes during the grass pollen allergen exposure challenge from time-point 0 to 4 hours on day 8.
TOSS is defined as the sum of the four individual ocular symptoms:
 ocular redness
 ocular itching
 watery eye
 gritty feeling
each scored on a 4-point categorical scale from 0-3 with
“0”= none
“1”=mild
“2”=moderate
“3”=severe

E.5.1.1

Timepoint(s) of evaluation of this end point

Every 15 minutes during the grass pollen allergen exposure challenge

E.5.2

Secondary end point(s)

 Change in ocular redness image score
 Total nasal symptom score (TNSS) is the sum of the symptoms “nasal congestion”, “rhinorrhea””, “itchy nose” and “sneezing”.
 Total asthma symptom score (TASS) is the sum of the symptoms “cough”, “wheeze”, “dyspnea”.
 Nasal airflow (AAR) will be assessed every 60 minutes during the four hours grass pollen allergen exposure challenge
Each individual symptom of TNSS and TASS will be scored on a 4-point categorical scale from 0-3 (where “0”= none, “1”=mild, “2”=moderate, “3”=severe). TNSS and TASS will be assessed every 15 minutes during the four hours grass pollen allergen exposure challenge.

E.5.2.1

Timepoint(s) of evaluation of this end point

TNSS and TASS will be scored every 15 minutes during the grass pollen allergen exposure challenge
AAR every 60 minutes during the grass pollen allergen exposure challenge

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

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)

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

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

two dosage groups each vs. placebo in a cross over design

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

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:

107

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

Yes

F.3.2

Patients

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

107

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

2020-01-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-04-22

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