Patients Suffering from Mite-Induced Allergic Rhino-Conjunctivitis Without or With Controlled Asthma MedDRA version: 19.1 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 effec-tive method of contraception during the entire study (implant, intrauterine device, male/female sterilization, hormonal contraception, sexual abstinence) or being post-menopausal for at least 1 year or sterilized women) outpatients, 18–64 years old (please also refer to section XI.3.). 2.Moderate to severe mite-induced rhino-conjunctivitis of at least 2 year according to the ARIA guidelines (please see the definition of moderate to severe rhino-conjunctivitis in the section III.2. Classification of Allergic Rhinitis). 3.Positive specific SPT (wheal diameter of 3 mm or larger than saline control) at screening for both mite extracts (Der p., and Der f.). 4.Written informed consent. 5.Positive nasal provocation test at screening (PNIF reduction by = 20% and symptom score increase by = 2 score points or PNIF reduction by = 40%). 6.Minimum level of rhinitis symptoms in a mite exposure challenge (baseline TNSS =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Allergen-specific immunotherapy (AIT) within the previous five years with mite-extracts and any current immunotherapy with another allergen. 2.History of hypersensitivity to any of the excipients used in LAIS® mites sublingual tablets or in placebo tablets (lactose monohydrate, cellulose microcrystalline, silica colloidal anhydrous and magnesium stearate). 3.Clinically relevant co-sensitization(s) (moderate-severe symptoms of AR/Asthma), e.g. to seasonal pollen or any animal hair and dander if regularly exposed and/or as demonstrated in SPT. 4.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 2015) at screening and/or severe asthma or history of uncontrolled/partly controlled asthma within 3 months prior to screening. 5.Subjects with reduced lung function forced expiratory volume in 1 second (FEV1) < 80% of the predicted value at screening. 6.Symptoms of or treatment for upper respiratory tract infection, acute sinusitis, acute otitis media, active tuberculosis or other relevant infectious process within 14 days of the first baseline AEC visit. 7.Clinically relevant nasal polyps, history of surgery either of paranasal sinus or of nasal turbinates and/or elective maxillofacial surgery within 6 months after planned treatment start (randomization). 8.History of anaphylaxis with cardiorespiratory symptoms (immunotherapy, exercise-induced, food allergy, drugs or an idiopathic reaction). 9.History of recurrent (defined as at least 2 or more episodes) generalized urticaria during the last 2 years. 10.History of drug-induced (including immunotherapy) facial and/or neck angioedema or a family (parents and siblings) history of hereditary angioedema. 11.Any clinically relevant chronic disease of = 6 months duration (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). 12.Systemic disease affecting the immune system (e.g., insulin-dependent diabetes, severe active autoimmune disease, immune complex disease or immune deficiency disease). 13.Contraindications to adrenaline (e.g. heart rhythm disorders, hyperthyroidism, Parkinson symptoms, glaucoma). 14.Concurrent use of prohibited medication(s) or inadequate wash-out of medication prior to SPT/NPT and AEC exposition. Other medications will be permitted, if they are not expected to interfere with the ability of the patient to participate in the study and provided they have been on a stable regimen (i.e., the same daily dosage and route of administration) for 4 weeks prior to screening. 15.Immunosuppressive treatment (ATC code L04 or L01) within 3 months prior to the screening visit. 16.Treatment with antidepressant medication with antihistaminic effect (e.g. doxepin, mianserin) 17.Treatment with antipsychotic medications with antihistaminic effect (e.g. chlorpromazine, levomepromazine, clozapine, olanzapine, thioridazine). 18.Treatment with anti-IgE drugs (e.g. omalizumab) within 130 days / 5 half-lives (whichever is the longest before 1st dosing). 19.Treatment with systemic ß-blockers. 20.Use of an investigational drug within 30 days / 5 half-lives of the drug (whichever is the longest prior to screening). 21.Direct family members of th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Change over time (time frame 6 months) in the TNSS in response to mite provocation in an AEC for 3 verum groups compared to placebo at V5 (final AEC) versus V1 (baseline AEC).;Secondary Objective: • Change over time in the TASS in response to mite provocation in an AEC for the 3 verum groups compared to placebo at V5 versus V1. • Assessment of the responder/non-responder rate in TNSS in response to mite provocation in an AEC. The responder are the patients demonstrating an improvement of 30% or more in TNSS at V5 compared to V1 (at time points 60–90 min). • Change over time in PNIF, VAS, cumulative VAS (for four symptoms for TNSS) in response to mite provocation in an AEC for the 3 verum groups compared to placebo at V5 versus V1. • Safety data obtained by physical examination and spirometry (FEV1, FEV1/FVC, MEF 25, 50, 75% and PEF). • Number of events and number of subjects affected by TEAEs and SAEs, local and systemic reactions, AEs leading to treatment discontinuation as well as analyses of early (occurring within 30 min after IMP intake) or delayed reactions (occurring later than 30 min after IMP intake).;Primary end point(s): Change over time (time frame 6 month) in the TNSS during AEC-challenge: scale from 0–3, total score up to 12 , in response to mite provocation in an AEC for 3 verum groups compared to placebo at V5 (final AEC) versus V1 (baseline AEC);Timepoint(s) of evaluation of this end point: Visit 1 and Visit 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • change over 6 months in the TASS: scale from 0–3 per symptom, total score up to 18, in response to mite provocation in an AEC for the 3 verum groups compared to placebo at V5 versus V1 • assessment of the responder/non-responder rate in TNSS. The responder are the patients demonstrating an improvement of 30% and more in TNSS at V5 compared to V1 at time points 60–90 min). The non-responder are the patients demonstrating an improvement of less than 30% and/or the patients demonstrating no change in TNSS and/or decrease in TNSS at V5 compared to V1 (at time points 60–90 min) • change over 6 months in PNIF in response to mite provocation in an AEC for the 3 verum groups compared to placebo at V5 versus V1 • change in VAS at 60 and 90 min in the 3 verum groups compared to placebo at V5 versus V1 • change in cumulative VAS for 4 symptoms of TNSS (maximal 400 mm, 100 mm per symptom) at V5 compared to V1 Safety: • safety data obtained by physical examination, spirometry (FEV1, FEV1/FVC, MEF 25, 50, 75% and PEF) • number of events and number of subjects affected by TEAEs and SAEs, local and systemic reactions, AEs leading to treatment discontinuation, as well as early (occurring within 30 min after IMP intake) or delayed reactions (occurring later than 30 min after IMP intake);Timepoint(s) of evaluation of this end point: Visit 1 and Visit 5 | — |
Countries
Germany
Contacts
Public ContactClinical Trials Information
Sacura GmbH
Outcome results
None listed