seasonal grass pollen-induced allergic rhinoconjunctivitis MedDRA version: 20.0 Level: LLT Classification code 10036019 Term: Pollen allergy System Organ Class: 100000004870 MedDRA version: 20.0 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853
Conditions
Interventions
Product Name: LAIS Grass Sublingual Tablets
Product Code: [LAIS Grass]
Pharmaceutical Form: Tablet
Current Sponsor code: LAIS Grass
Other descriptive name: LAIS Grass tablets
Concentration unit: AU/ml
Sponsors
LOFARMA S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
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 =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 Are the trial subjects under 18? yes 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: • 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;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);Timepoint(s) of evaluation of this end point: 14 days of h | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 .;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 | — |
Countries
Italy
Contacts
Public ContactCRO
CD PHARMA GROUP SRL
Outcome results
None listed