Patients Suffering from Mite-Induced Allergic Rhino-Conjunctivitis Without or With Controlled Asthma MedDRA version: 20.0 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853
Conditions
Sponsors
Lofarma S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female (not breastfeeding, with negative 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) outpatients, 18–64 years old. 2. Moderate to severe mite-induced ARC of at least 2 years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. 3. Positive specific SPT (wheal size diameter of =3 mm for histamine control AND wheal size diameter of >= 3 mm larger than saline control) at screening for Der. f. or Der. p. 4. Serum specific IgE to Der. f. or Der. p. (>0.7 kU/l). 5. Positive nasal provocation test at V1: mean LSS, as total score of applied allergen dosages divided by the number of allergen dosages, =5. 6. Subject must be willing and able to comply with the trial protocol 7. Written informed consent. Are the trial subjects under 18? no 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 184 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Allergen Immunotherapy (AIT) within the previous five years with mite-extracts and any current immunotherapy with another allergen. 2. Clinically relevant hypersensitivity to any of the excipients used in LAIS® mites sublingual tablets, in placebo tablets, in the rescue medications (prednisone, desloratadine, mometasone) and/or SPT and/or NPT solutions (lactose monohydrate, cellulose microcrystalline, silica colloidal anhydrous, magnesium stearate, sodium carboxymethyl cellulose, silicon dioxide, carmellose sodium, glycerol, citric acid monohydrate, sodium citrate dihydrate, polysorbate 80, benzalkonium chloride, maize starch, hypromellose, hydro treated vegetable oil (Type 1), titanium dioxide, macrgol 400, indigocarmin-aluminiumsalt, phenol, sodiumphospate dihydrate, disodium phosphate dodecahydrate, sodium chloride, human albumin) and/or active substances of the rescue medication (prednisone, desloratadine, mometasone). 3. Clinically relevant co-sensitization(s) (moderate to severe symptoms of ARC/asthma against co-allergens), e.g. to seasonal pollen and/or any animal hair and dander, if regularly exposed and/or as demonstrated in SPT. 4. Co-sensitizations with the allergen reaction to co-allergens having a wheal size diameter larger than that of house dust mite allergens in SPT. 5. Asthma requiring treatment other than short-acting inhaled ß2- agonists and low-dose inhaled corticosteroids [e.g. Step 2 (patients receiving Leucotriene receptor antagonists (LTRA) to Step 5, GINA- definition 2018] at screening and/or severe asthma or history of uncontrolled/partly controlled asthma within 3 months prior to screening. 6. Subjects with reduced lung function forced expiratory volume in 1 second (FEV1) <80% of the predicted value at screening. 7. Symptoms of or treatment for acute inflammation of the nose, upper respiratory tract infection, acute sinusitis, acute otitis media, active tuberculosis or other relevant infectious process within 14 days of the first baseline TNPT visit. 8. Clinically relevant nasal polyps, history of surgery either of paranasal sinus or of nasal turbinates, and/or elective maxillofacial surgery within 6 months before planned treatment start (randomization). 9. Diagnosis of choanal atresia, chronic rhinosinusitis with nasal polyps, septal perforation, severe septal deviation, atrophic rhinitis, adenoids obstructing nasal ventilation. 10. History of anaphylaxis Grade 3 or 4 according to Ring et al. (2014). 11. History of recurrent (defined as at least 2 or more episodes) generalized urticaria during the last 2 years. 12. History of immunotherapy-induced facial and/or neck angioedema or a family (parents and siblings) history of hereditary angioedema. 13. Any clinically relevant chronic disease (e.g. cystic fibrosis, emphysema, malignancy, malabsorption or malnutrition, renal or hepatic abnormality, chronic infections, or any other diseases that, in the opinion of the investigator, would interfere with the trial evaluations or the safety of the subjects). 14. Systemic disease affecting the immune system (e.g., insulin dependent diabetes, severe active autoimmune disease, immune complex disease or immune deficiency disease). 15. Contraindications to adrenaline (e.g. heart rhythm disorders, hyperthyroidism, Parkinson symptoms, glaucoma). 16. Concurrent use of prohibited medication(s) or inadequate wash-out of medication prior to SPT/NPT. Other medications will be permitted, if they are not expected to interfere w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this clinical trial is to determine the optimal effective and safe dose of tablet-based ‘sublingual specific immunotherapy’ (SLIT) with the monomeric allergoid LAIS® dermatophagoides sublingual tablets, administered once daily (o.d.), to adults with mite-induced ARC undergoing allergen-specific provocation with Titrated Nasal Provocation Test (TNPT) and natural ‘in-field’ allergen exposure.;Secondary Objective: Not applicable;Primary end point(s): Change over time (final TNPT vs baseline TNPT) in the mean Lebel’s Symptoms Score (LSS) in response to mite provocation for 3 verum groups compared to placebo.;Timepoint(s) of evaluation of this end point: baseline TNPT (V1) and final TNPT (V10) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Change over time (difference interim TNPT vs baseline TNPT) in the mean Lebel’s Symptoms Score (LSS) in response to mite provocation for 3 verum groups compared to placebo and between active groups for dose-response evaluation. ? Percentage of subjects with at least 10-fold increase in the dose eliciting a positive nasal provocation test for 3 verum groups compared to placebo. ? Mean Lebel’s Symptoms Score (LSS) in interim TNPT and final TNPT in the 3 verum groups compared to placebo (comparison between groups in the LSS). ? Change over time (difference final TNPT and interim TNPT vs baseline TNPT) in PNIF in response to mite provocation (the highest between the two evaluations at 10min and 45 min from the last dose administered) for the 3 verum groups compared to placebo. ? Change over time (difference final TNPT and interim TNPT vs baseline TNPT) in VAS for 4 nasal symptoms and cumulative VAS (maximal 400 mm, 100 mm per symptom) in response to mite provocation in the 3 verum groups compared to placebo. ? Mean Combined Symptom-Medication score (CSMS, range 0-6), mean dSS, and mean dMS in the 3 verum groups compared to placebo during the period 1st November to 31st December 2019 of diary documentation. ? Mean change from baseline (2 weeks run-in) of the CSMS in the period 1st November to 31st December 2019 of diary documentation in the 3 verum groups compared to placebo. ? VAS score for 4 nasal symptoms and cumulative VAS (maximal 400 mm, 100 mm per symptom) in the three verum groups compared to placebo at each control visit. ? Safety data obtained by physical examination, vital signs, laboratory variables and spirometry (FEV1, FEV1/FVC, PEF and optinal MEF 25,50,75% and or MEF25-75) ? Number of events and number of subjects affected by TEAEs and SAEs, local and systemic reactions, as well as analyses of early (occurring within 30 min after IMP intake) or delayed reactions (occurring later than 30 min after IMP intake). ? Serum specific i | — |
Countries
Germany
Contacts
Public ContactClinical Trials Information
Sacura GmbH
Outcome results
None listed