Clinical Trials Register

Summary
EudraCT Number:	2019-001532-65
Sponsor's Protocol Code Number:	LGT03-19
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-07-08
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-001532-65

A.3

Full title of the trial

A prospective, multicenter, double-blind, placebo-controlled randomized study to assess efficacy and safety of LAIS® Grass pollen tablets in patients with seasonal grass pollen-induced allergic rhinoconjunctivitis

Studio prospettico, multicentrico, in doppio cieco, placebo-controllato, randomizzato per valutare l’efficacia e la sicurezza delle compresse di LAIS® Grass in pazienti con rinocongiuntivite allergica stagionale indotta dal polline di graminacee

A.3.1

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

Efficacy and Safety of sublingual immunotherapy with LAIS® Grass pollen tablets in patients with seasonal grass pollen-induced allergic rhinoconjunctivitis

Efficacia e Sicurezza dell'immunoterapia sublinguale con compresse di di LAIS® Grass in pazienti con rinocongiuntivite allergica indotta dal polline di graminacee

A.3.2

Name or abbreviated title of the trial where available

LAIS® Grass pollen tablets in seasonal grass pollen-induced allergic rhinoconjunctivitis

Compresse di LAIS® Grass in pazienti con rinocongiuntivite allergica indotta dal polline di graminac

A.4.1

Sponsor's protocol code number

LGT03-19

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	LOFARMA S.P.A.
B.1.3.4	Country	Italy
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	Lofarma S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CD PHARMA GROUP SRL
B.5.2	Functional name of contact point	CRO
B.5.3	Address:
B.5.3.1	Street Address	PIAZZA DE ANGELI, 7
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20146
B.5.3.4	Country	Italy
B.5.4	Telephone number	0289051076
B.5.5	Fax number	0289051088
B.5.6	E-mail	info@cdpharma.it

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	LAIS Grass Sublingual Tablets
D.3.2	Product code	[LAIS Grass]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Sublingual use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	LAIS Grass
D.3.9.3	Other descriptive name	LAIS Grass tablets
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	1000
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
D.2.1.1.1	Trade name	AERIUS - 5 MG 20 COMPRESSE RIVESTITE CON FILM USO ORALE
D.2.1.1.2	Name of the Marketing Authorisation holder	MERCK SHARP e DOHME LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Desloratadina
D.3.2	Product code	[Desloratadina]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Desloratadina
D.3.9.1	CAS number	100643-71-8
D.3.9.2	Current sponsor code	Desloratadina
D.3.9.3	Other descriptive name	Desloratadine
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 3
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	NASONEX - SPRAY NASALE 0.05% 140 EROGAZIONI 50 MCG/SPRUZZO
D.2.1.1.2	Name of the Marketing Authorisation holder	MSD ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Mometasone Furoato
D.3.2	Product code	[Mometasone Furoato]
D.3.4	Pharmaceutical form	Nasal spray, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MOMETASONE FUROATO
D.3.9.1	CAS number	105102-22-5
D.3.9.2	Current sponsor code	Mometasone Furoato
D.3.9.3	Other descriptive name	mometasone furoate
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 4
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	BF2 - 5 MG COMPRESSE 20 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BF RESEARCH S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Prednisone
D.3.2	Product code	[Prednisone]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PREDNISONE
D.3.9.1	CAS number	53-03-2
D.3.9.2	Current sponsor code	Prednisone
D.3.9.3	Other descriptive name	Prednisone
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 5
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	LEVOSTAB - 0.5 MG/ML SPRAY NASALE, SOSPENSIONE FLACONE 10 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	GRUNENTHAL ITALIA S.R.L.
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	Levocabastina
D.3.2	Product code	[Levocabastina]
D.3.4	Pharmaceutical form	Eye drops, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVOCARNITINA CLORIDRATO
D.3.9.1	CAS number	79516-68-0
D.3.9.2	Current sponsor code	Levocabastina
D.3.9.3	Other descriptive name	Levocabastine
D.3.10	Strength
D.3.10.1	Concentration unit	Gtt drop(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Tablet
D.8.4	Route of administration of the placebo	Sublingual use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

seasonal grass pollen-induced allergic rhinoconjunctivitis

rinocongiuntivite allergica stagionale indotta dal polline di graminacee

E.1.1.1

Medical condition in easily understood language

seasonal grass pollen-induced allergic rhinoconjunctivitis

rinocongiuntivite allergica stagionale indotta dal polline di graminacee

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

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	10036019
E.1.2	Term	Pollen 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.1.3

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 study is to evaluate the efficacy and safety of tablet-based sublingual immunotherapy (SLIT) with the monomeric allergoid LAIS® Grass tablets compared to placebo in patients with grass pollen-induced allergic rhinoconjunctivitis with or without controlled asthma

L’obiettivo primario dello studio è di valutare l’efficacia e la sicurezza dell’immunoterapia sublinguale (SLIT) con compresse di allergoide monomerico LAIS® Grass comparata al placebo in pazienti con rinocongiuntivite allergica indotta da polline di graminacee in presenza o assenza di asma controllato.

E.2.2

Secondary objectives of the trial

• Assessment of the correlation between extent of positivity to Nasal Provocation Test and efficacy of the therapy;
• Assessment of average CSMS calculated on the 2 weeks with the highest symptom/medication scores of the placebo group at an individual site
• Assessment of average CSMS calculated with alternative symptoms-medication scoring: dSS = 0-18 (runny nose, blocked nose, sneezing, itchy nose, ocular itching/grittiness/redness and ocular tearing, each assessed on a scale from 0 to 3), dMS = 0-20 (oral antihistamine score, 6; ocular antihistamines score, 6, nasal corticosteroid score, 8). Consequently, the CSMS ranges from 0 to 38;
• Loss of asthma control (for asthmatic patients only) based on consensus-based GINA symptom control tool;
• Assessment of primary and secondary endpoints in the age subgroup of adolescents

• Valutazione della correlazione tra entità della positività al Test di Provocazione Nasale e l’efficacia della terapia;
• Valutazione del CSMS medio calcolato nelle due settimane con i punteggi sintomi/terapia più alti del gruppo placebo in ogni singolo centro;
• Valutazione del CSMS medio calcolato con un punteggio sintomo/terapia alternativo: dSS = 0-18 (naso che gocciola, naso congestionato, starnutazione, prurito al naso, prurito oculare/granulosità/rossore e lacrimazione; ognuno valutato con un scala da 0 a 3), dMS = 0-20 (punteggio antistaminico orale, 6; punteggio antistaminico oculare, 6, punteggio corticosteroide nasale, 8). Di conseguenza, il range CSMS da 0 a 38.
• Perdita di asma controllato (solo per pazienti asmatici) basato sullo strumento di controllo dei sintomi GINA
• Valutazione degli endopoint primari e secondari nel sottogruppo degli adolescenti

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female (not breastfeeding, with negative urine pregnancy test and using either a highly effective method of contraception during the entire study or being post-menopausal for at least 1 year or sterilized women) or male patients, aged 12–64 years with a history of at least 2 years of grass pollen induced allergic rhinoconjunctivitis (ARC) with or without seasonal controlled allergic asthma [From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2018. Available from: http://www.ginasthma.org],;
2. Moderate/Severe (interfering with usual daily activities or sleep) ARC defined according to ‘Allergic Rhinitis and it impact on Asthma’ (ARIA) guidelines (Brozek et al., 2017)
a) Requiring treatment (either antihistamines or nasal corticosteroids) during the grass pollen season and
b) Retrospective Symptoms Score >10 out of pharmacotherapy or >4 under pharmacotherapy, as sum of the score (0-3) for each of the six nasal and conjunctival symptoms referred to the previous grass pollen season (range 0-18) (EMA/414476/2011);
3. Positive clinical history of grass pollen allergy, proven by:
• The majority of clinical symptoms appearing during the grass pollen season;
• Specific IgE reactivity (immuneCAP) >= Class 2 to major allergens of Phleum pratense (if specific IgE have been recently examined in the year 2019 before the inclusion in the study, for instance at the moment of first clinical diagnosis, the results can be used as screening data);
• Positive Skin Prick Test to Phleum pratense (or Grass mix extract including Phleum pratense) (wheal diameter >= 3 mm, negative control < 2 mm);
• Positive reaction to Titrated Nasal Provocation Test (TNPT) with Lebel’s symptoms score (LSS) >=6;
• Wash-out of pharmacological treatment interfering with the test is required prior to the SPT/TNPT (see dedicated section).
4. Compliance and ability of the patient to complete a patient’s diary for self-evaluation of the symptoms and anti-symptomatic medication, and treatment compliance;
5. Signed and dated patient´s Informed Consent

Criteri di inclusione:
1. Donne (non in allattamento, con test di gravidanza su urine negativo e che utilizzino un metodo contraccettivo altamente efficace durante l'intero studio o che siano in post-menopausa da almeno 1 anno o che siano sterili) o uomini, tra i 12 e i 64 anni con una storia di almeno 2 anni di rinocongiuntivite allergica indotta da polline di graminacee (ARC) con o senza asma allergico [From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2018. Available from: http://www.ginasthma.org],;
2. ARC Moderata/Grave (che interferisce con le normali attività giornaliere e/o il sonno) definita in accordo con le line guida ARIA “ Rinite allergica e suo impatto sull’Asma” (Brozek et al., 2017) e che
a) richieda trattamento (antistaminici o corticosteroidi nasali) durante la stagione pollinica delle graminacee e
b) con Punteggio retrospettivo dei sintomi >10 (se fuori da terapia farmacologica) o > 4 (se in terapia farmacologica), come somma del punteggio (0-3) per ognuno dei sei sintomi nasali e congiuntivali riferiti alla stagione pollinica delle graminacee precedente (range 0-18)(EMA/414476/2011);
3. Storia clinica positiva di allergia a polline di graminacee, provata da:
• La maggioranza di sintomi clinici che appaiono durante la stagione pollinica delle graminacee;
• Reattività IgE specifica (ImmunoCAP) >= Classe 2 verso gli allergeni maggiori del Phleum pratense (se le IgE specifiche sono state recentemente esaminate nell’anno 2019 prima dell’inclusione nello studio, per esempio al momento della prima diagnosi clinica, i risultati possono essere usati allo screening));
• Skin Prick Test positivo al Phleum pratense (o un mix di estratti che includono Phleum pratense) (diametro del pomfo >= 3 mm, controllo negativo < 2 mm);
• Reazioni positive al Test di Provocazione Nasale (TNPT) con il punteggio dei sintomi di Lebel (LSS) >=6;
• È richiesto il wash-out dal trattamento farmacologico che interferisce con il test prima del SPT/TNPT (vedere la sezione dedicate).

4. Compliance e abilità del paziente nel completare il diario paziente per una auto-valutazione dei sintomi e della terapia antisintomatica, compliance al trattamento;
5. Ottenimento del Consenso Informato firmato e datato.

E.4

Principal exclusion criteria

Clinically relevant hypersensitivity to any of the excipients used in LAIS® Grass sublingual tablets or in placebo tablets (lactose monohydrate, cellulose microcrystalline, silica colloidal anhydrous and magnesium stearate);
History of intolerance to the rescue medications (prednisone, desloratadine, mometasone, levocabastine) and solution for nasal test, or their excipients; conditions representing contraindications to the rescue medications;
Previous immunotherapy with grass allergens or cross-reacting allergens within the last 5 years;
Ongoing immunotherapy with any allergen;
Existing or intended pregnancy, lactation and/or lack of adequate contraceptive protection;
History of moderate to severe perennial allergic rhinitis requiring medication, caused by perennial allergen (i.e. house dust mites);
History of clinically relevant allergic rhinitis and/or asthma caused by an allergen to which the subject is regularly exposed (i.e. pets’ and horse hair or dander);
History of clinically relevant seasonal allergic rhinitis and/or asthma due to genuine sensitization to tree pollens (Oleaceae, Betulaceae Corylaceae Cupressaceae), main weed pollens (Urticacee), Chloridoideae grass pollen (Cynodon Dactylon), moulds (Alternaria),with diffusion adjacent to the start of and potentially overlapping the grass pollen season (each co-sensitization has to be evaluated for relevance with relation to the expected exposure in each geographic area and climatic zone; for example, a subject with positive skin test to Parietaria, history of symptoms clinically related to Parietaria exposure in a region with expected significant levels of Parietaria pollens has to be excluded);
Symptoms of or treatment for acute inflammation of the nose, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process within 14 days of the baseline TNPT visit;
Diagnosed of choanal atresia, nasal polyps, septal perforation, severe septal deviation, atrophic rhinitis, adenoids obstructing nasal ventilation;
History of surgery either of paranasal sinus or of nasal turbinates, and/or elective maxillofacial surgery within 6 months before planned treatment start (randomization);
Severe asthma or history of uncontrolled/partly controlled asthma within 3 months prior to screening (based on consensus-based GINA symptom control tool);
History of chronic rhinosinisitit

Ipersensibilità clinicamente rilevante agli eccipienti usati in LAIS® Grass compresse sublinguali o nelle compresse di placebo (lattosio monoidrato, cellulosa microcristallina, silice colloidale anidra e magnesio stearato);
Storia di intolleranza alla terapia di supporto (prednisone, desloratadina, mometasone, levocabastina) e alla soluzione per il test nasale o i suoi eccipienti; condizioni che rappresentano controindicazioni alla terapia di supporto;
Immunoterapia precedente con allergeni di graminacee o allergeni cross-reattivi entro 5 anni;
Immunoterapia in corso con un allergene;
Gravidanza in corso o desiderata, allattamento e/o mancanza di adeguata anticontraccezione;
Storia di una rinite allergica perenne da moderata a grave che richieda terapia, causata da allergeni perenni (per esempio acari della polvere di casa);
Storia di una rinite allergica clinicamente rilevante e/o asma causato da un allergene a cui il soggetto è regolarmente esposto (per esempio pelo o epitelio di animale domestico o di cavallo);
Storia di una rinite allergica stagionale clinicamente rilevante e/o asma dovuto a una sensibilizzazione autentica ai pollini di alberi (Oleaceae, Betulaceae Corylaceae Cupressaceae), ai pollini delle principali erbe infestanti (Urticacee ), ai polline di erba Chloridoideae (Cynodon Dactylon), a muffe (Alternaria), con diffusione potenzialmente vicina o sovrapposta all’inizio della stagione pollinica delle graminacee (ogni co-sensibilizzazione va valutata per stabilirne la rilevanza in relazione all’esposizione attesa in ogni area geografica e zona climatica; per esempio, sarò escluso un soggetto con uno Skin Prick Test positivo per Parietaria , storia di sintomi clinicamente correlati alla esposizione alla Parietaria in una regione con significativi livelli attesi di pollini di Parietaria);
Sintomi di o trattamento per infiammazione acuta del naso, infezione del tratto superiore delle vie respiratorie, sinusite acuta, otite media acuta, o altre infezioni rilevanti entro 14 giorni dalla visita TNPT di baseline;
Atresia coanale diagnosticata, polipi nasali, perforazione del setto, grave deviazione del setto, rinite atrofica, adenoidi che ostruiscono la ventilazione nasale;
Storia di chirurgia dei seni paranasali o dei turbinati nasali, e/o chirurgia elettiva maxillofacciale entro 6 mesi prima dell’inizio del trattamento pianificato (randomizzazione);
Asma grave o storia di asma non controllato/parzialmente controllato entro 3 mesi prima dello screening (in base allo strumento di controllo GINA);
Storia di rinosinusite cronica

E.5 End points

E.5.1

Primary end point(s)

Average daily total Combined Symptom-Medication score (CSMS) based on an equal weight of the dSS and of the dMS for the 14 days of highest pollen load within the peaks of the grass pollen season taking into account:
• Daily rhinoconjunctivitis total Symptom Score (dSS) of the six rhinoconjunctivitis symptoms over the previous 24 hours, which include itching, sneezing, rhinorrhea, obstruction, ocular itching/grittiness/redness and ocular tearing with scale from 0-3 per symptom (maximum score 18 points / divided by 6 symptoms = 3 points)
and
• Daily Medication Score (dMS) over the previous 24 hours. If more than 1 class of rescue medication is used on a particular day, the highest score will be retained for the dMS of that day (maximum score = 3)

Media del Combined Symptom-Medication score (CSMS) totale quotidiano basato su un eguale peso del dSS e del dMS per i 14 giorni di maggior carico di polline entro i picchi della stagione pollinica delle graminacee, prendendo in considerazione:
• Daily rhinoconjunctivitis total Symptom Score (dSS) dei sei sintomi per la rinocongiuntivite nelle precedenti 24 ore, che includono prurito, starnutazione, rinorrea, ostruzione, prurito oculare/granulosità/rossore e lacrimazione oculare con scala da 0-3 per sintomo (Massimo score 18 punti/divisi per 6 sintomi = 3 punti)
e
• Daily Medication Score (dMS) nelle precedenti 24 ore. Se è stata usata più di 1 classe di terapia di supporto in un particolare giorno, il punteggio più alto sarà mantenuto per il dMS di quel giorno (punteggio Massimo = 3)

E.5.1.1

Timepoint(s) of evaluation of this end point

14 days of highest pollen load within the peaks of the grass pollen season

14 giorni di maggior carico di polline entro i picchi della stagione pollinica delle graminacee

E.5.2

Secondary end point(s)

Average Combined Symptom-Medication score (CSMS); average Daily rhinoconjunctivitis total Symptom Score (dSS); Average Daily Medication Score (dMS); The “well days”, being defined as days of the entire grass pollen season with a maximum ARC symptom score of 2 and no rescue medication use (verum vs placebo); Excellence of rhinoconjunctivitis control during the entire grass pollen season = more than 50% well days in the grass pollen season;; Visual analogue scale (VAS) score, using a 100-mm scale; A global evaluation carried out by the patient for the entire grass pollen season, to evaluate the Treatment Satisfaction (verum vs placebo); A global evaluation carried out by the patient in the overall comparison of the current grass pollen season versus the previous season (previous year); Safety of the treatment by means of physical examinations, blood and urine sampling, description of the adverse events (frequency, intensity, severity and duration of adverse events) and safety laboratory data following treatment with LAIS® Grass tablets .

Combined Symptom-Medication score (CSMS) medio; Daily rhinoconjunctivitis total Symptom Score (dSS) medio:; Daily Medication Score (dMS) medio; I “well days”, definiti come giorni dell’intera stagione pollinica delle graminacee con un punteggio massimo dei sintomi di 2 e nessuna terapia di supporto utilizzata (verum vs placebo); eccellenza del controllo di rinocongiuntivite durante l’intera stagione pollinica = più del 50% di well days nella stagione pollinica; Punteggio della scala visuo-analogica (VAS), usando una scala 100-mm; Valutazione globale eseguita dal paziente per l’intera stagione pollinica, per valutare la Soddisfazione al Trattamento (verum vs placebo); Valutazione globale eseguita dal paziente in una comparazione complessiva della corrente stagione pollinica delle graminacee rispetto alla stagione precedente (anno antecedente); Sicurezza del trattamento tramite esame fisico, prelievi di sangue e urine, descrizione degli eventi avversi ( frequenza, intensità, gravità e durata degli eventi avversi) e dei dati di sicurezza di laboratorio dopo il trattamento con le compresse LAIS® Grass

E.5.2.1

Timepoint(s) of evaluation of this end point

a) during the days with = 50 pollen/m3, b) the entire grass pollen season until the study end (verum vs placebo);; a) for the 14-days of highest pollen load in the peak grass pollen season, b) during the days with = 50 pollen/m3, c) over the entire grass pollen season until the study end (verum vs placebo); a) for the 14-days of highest pollen load in the peak grass pollen season, b) during the days with = 50 pollen/m3, c) over the entire grass pollen season until the study end (verum vs placebo); entire grass pollen season; entire study duration; entire grass pollen season; at the end of study; total study duration

a) durante i giorni con = 50 pollini/m3,
b) l’intera stagione pollinica delle graminacee fino alla fine dello studio (verum vs placebo);; a) per i 14 giorni di massimo carico di polline nel picco stagionale pollinico di graminacee,
b) durante i giorni con = 50 pollini/m3
c) durante l’intera stagione pollinica delle graminacee fino alla fine dello studio (verum vs placebo);; a) per i 14 giorni di massimo carico di polline nel picco stagionale pollinico di graminacee,
b) durante i giorni con = 50 pollini/m3
c) durante l’intera stagione pollinica delle graminacee fino alla fine dello studio (verum vs placebo);; intera stagione pollinica delle graminacee; intera durata dello studio; intera stagione pollinica; fine dello studio; durante l'intero studio

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

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

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

Information not present in EudraCT

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

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.1.1.1

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:

176

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

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

264

F.4.2

For a multinational trial

F.4.2.1

In the EEA

264

F.4.2.2

In the whole clinical trial

264

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)

the subject, at the end of study, will be followed according to the normal clinical practice

i pazienti al termine della sperimentazione saranno seguiti da normale pratica clinica

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

2019-08-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-12

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials