Treatment of tree pollen-induced allergic rhinoconjunctivitis MedDRA version: 20.0 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853
Conditions
Interventions
Product Name: Lais Frühblüher sublingual Drops
Product Code: Lais Frühblüher sublingual Drops
Pharmaceutical Form: Oromucosal drops
Pharmaceutical form of the placebo: Oromucosal drops
Route of admini
Sponsors
Lofarma S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed and dated Informed Consent Form by a legally competent patient • Female or male patients aged 18–64 years • Being in good physical and mental health • Confirmed normal renal and liver function (including non-clinically signifcant deviations as defined per laboratory ranges) • For females: non-pregnant, non-lactating with adequate contraception or unable to bear children (e.g. tubal ligation, hysterectomy, or post-menopausal (defined as a minimum of one year since the last menstrual period)) • Having the diagnosis of allergy based on all the following criteria: • A medical history of moderate to severe allergic rhinoconjunctivitis for birch pollen allergens for at least 2 years (definition of allergy severity according to ARIA (Bousquet et al., 2001)) • A positive skin prick test (SPT, wheal diameter =3 mm) to birch pollen allergens, positive control (histamine) wheal =3 mm, negative control (NaCl) wheal =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Simultaneous participation in other clinical trials or previous participation within 30 days before inclusion • Previous immunotherapy with birch pollen allergens within the last 5 years • Ongoing immunotherapy with birch pollen allergens or any other allergens • Being in any relationship with or dependence on the Sponsor, CRO and/or Investigator • Inability to understand instructions/study documents • History of severe systemic reactions and/or anaphylaxis to food (e.g. peanut, seafood), Hymenoptera venom (e.g. bee, wasp stings), medication (e.g. penicillin), etc. • History of hypersensitivity to the excipients of the investigational product or placebo • Mild persistent to severe persistent asthma, partly controlled or uncontrolled asthma according to GINA guidelines (GINA 2014) • Chronic asthma or emphysema, i.e. FEV1 <80% of the patient’s reference value or PEF <80% of the patients´ individual optimal value • Respiratory tract infection or exacerbation of asthma within 4 weeks before the screening • Patients symptomatic to any seasonal inhaled allergens circulating during the study period (e.g.hazel) confirmed by medical history and SPT • Patients symptomatic to any perennial inhaled allergens (e.g. cat, dog, mites), to which the patients are regularly exposed during the study period, confirmed by medical history and SPT • Infections in the oral cavity with severe symptoms • Moderate to severe oral allergy syndrome caused by tree pollen-food cross-reactivity • Oral inflammation or wounds • History of significant renal disease or chronic hepatic disease • Malignant active disease (ongoing or within the five past years) • Severe autoimmune disease • Immune defects including immunosuppression, immunopathies • Vaccination, use of systemic immunosuppressive medications (e.g. methotrexate or cyclosporine A) or a blood transfusion one month before screening • General inflammatory, severe, acute or chronic inflammatory diseases • Other chronic diseases such as severe congestive heart failure, cardiovascular insufficiency, active gastric ulcer, inflammatory bowel disease, uncontrolled diabetes mellitus, etc. • Intake of antidepressant drugs with potent antihistamine properties such as tricyclic antidepressants (e.g. doxepin, amitriptyline, desipramine, imipramine, etc.) • Administration or planned administration of anti-IgE antibodies, mast cell stabilizers or anti-leukotriene agents • Use of systemic beta-blockers • Active tuberculosis • Contraindication for the use of adrenaline (including hyperthyroidism) • Contraindication for CPT (eye diseases except for anomalies of refraction, active allergic conjunctivitis, contact lenses, antiallergic therapy) • Known positive serology to Human Immunodeficiency Virus-1/2, Hepatitis B Virus or Hepatitis C Virus • Females who are pregnant, lactating, or of child-bearing potential and not using adequate contraceptives • Use of corticosteroids (oral, topic or nasal) or anti-histaminic drugs before screening visit. Exception made for routine medication for asthma control in asthmatic patients • Planned vaccination during the study (e.g. against flu, pneumococae, etc.) • Clinically relevant laboratory values, i.e. grade =2 according to the FDA Guidance for Industry for preventive Vaccine Trials (FDA 2007) • Patients, who the Investigator believes will not comply with the study protocol (patients with alcohol/drug abuse, history of serious psychiatric disorder, or who unwilling to give informed c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to assess the safety and clinical tolerability of Lais® Frühblüher sublingual drops in patients with birch pollen-induced allergic rhinoconjunctivitis.;Secondary Objective: The secondary objectives of this trial are to assess •the impact on the immunological status by comparing actively treated and placebo patients •the clinical impact with regard to conjunctival reactivity by comparing actively treated and placebo patients based on the reduction of conjunctival tissue reactivity following Conjunctival Provocation Test (CPT) ;Primary end point(s): Safety and clinical tolerability of Lais tree pollen sublingual drops treatment will be assessed by: •Solicited adverse events including local reactions at the administration site (oropharyngeal and gastrointestinal symptoms) and systemic allergic reactions after investigational product administration. ;Timepoint(s) of evaluation of this end point: Solicited adverse events including local reactions at the administration site (oropharyngeal and gastrointestinal symptoms) and systemic allergic reactions as well as unsolicited adverse events will be evaluated after investigational product administration over the time frame of the entire treatment period between V2 and V6. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and clinical tolerability will also be assessed by: •Unsolicited adverse events •Proportion of patients who reached the maximum dose •Use of rescue medication during treatment phase •Physical examinations and vital signs •Laboratory tests (blood count, renal and liver function parameters) •Pulmonary function for asthmatic patients Clinical immunogenicity endpoints will include: •Production of Bet v1 specific IgE, IgA and IgG4 Clinical impact endpoints will include: •Conjunctival provocation test ;Timepoint(s) of evaluation of this end point: The proportion of patients who reached the maximum dose and the use of rescue medication will be evaluated over the time frame of the entire treatment period between V2 and V6. Physical examinations and vital signs will be evaluated over all visits (V1 - V6/V6b). Pulmonary function in asthmatic patients right before the intake of IMP will be evaluated over the time frame of the entire treatment period betwenn V2 and V6. Evaluation of blood count, renal and liver function-related parameters will be done at visits V1 and V6. Birch pollen specific Ige, IgA and IgG4 will be measured at visits V1 and V6. Conjunctival provocation testing will be evaluated at visits V1 and V6 or V6b. | — |
Countries
Germany
Contacts
Public ContactCoordinating Investigator
CRI - Clinical Research International Ltd.
Outcome results
None listed