Efficacy and Safety of sublingual immunotherapy with Allergoid LAIS® Grass tablets for patients with grass pollen-induced allergic rhinoconjunctivitis, a phase III study

INTERVENTION: Product Name: LAIS Grass tablets Product Code: LAIS Grass Tablets Pharmaceutical Form: Sublingual tablet INN or Proposed INN: LAIS Grass tablets Other descriptive name: Chemically modified extract (monomeric allergoid) from grass pollen extracts (Holcus lanatus 33 %, Phleum pratense 33%, Poa pratensis 33 %) Concentration unit: AgU antigen unit(s) Concentration type: equal Concentration number: 1000‐ Pharmaceutical form of the placebo: Sublingual tablet Route of administration of the placebo: Sublingual use CONDITION: Patients suffering from allergic rhinoconjunctivitis ; MedDRA version: 16.1 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853 Therapeutic area: Body processes [G] ‐ Immune system processes [G12] SECONDARY OUTCOME: Secondary end point(s): ‐Total Combined Score (TCS) (entire pollen season); ‐ 6 individual symptom scores of the Rhinoconjunctivitis Symptom Score (peak month and entire pollen season); ‐ Total Rhinoconjunctivitis Symptom Score (entire pollen season); ‐ Total Rescue Medication Score (entire pollen season); ‐ Asthma symptoms + use of asthma rescue medication (entire pollen season); ‐ clinical benefit of SLIT (reduction of rhinoconjunctivitis symptoms and rhinitis symptom control); ‐ Mean improvement in allergic severity S in CPT (baseline and visit V4); ‐ changes of the threshold allergen concentration for a positive response within CPT (baseline and V4) ; ‐The redness of the eye in CPT (assessed by a central observer); ‐ The “well days”(entire pollen season, maximum symptom score of 2, no rescue medication) ; ‐ Assessment of grass specific IgG4; ‐ A global evaluation (entire pollen season); ‐ Safety (physical examinations, adverse Events, safety laboratory data) ; ‐ Rhinoconjunctivitis Quality of Life (RQLQ) Timepoint(s) of evaluation of this end point: The peak of the grass pollen season, defined by those 30 consecutive days per centre with the highest local grass pollen counts, starting with at least “moderate” pollen concentrations (stage 2 according to Deutscher Wetterdienst Medizin‐Meteorologie, http://www.dwd.de) in the nearest pollen count station in that region; PRIMARY OUTCOME: Main Objective: The primary objective is to assess the efficacy of sublingual immunotherapy with the allergoid LAIS®Grass tablets by the total combined score (TCS) taking in account the rhinoconjunctivitis total symptom score (RTSS) of the six rhinoconjunctivitis symptoms (sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus and watery eyes and the total rescue medication score (TRMS) for the peak of the grass pollen season. Primary end point(s): The primary objective is to assess the efficacy of sublingual immunotherapy with the allergoid LAIS® Grass tablets by the total combined score (TCS) regarding the rhinoconjunctivitis total symptom score (RTSS) of the six rhinoconjunctivitis symptoms (sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus and watery eyes and the total rescue medication score (TRMS). Secondary Objective: ‐Total Combined Score (TCS) (entire pollen season); ‐ 6 individual symptom scores of the Rhinoconjunctivitis Symptom Score (peak month and entire pollen season); ‐ Total Rhinoconjunctivitis Symptom Score (entire pollen season); ‐ Total Rescue Medication Score (entire pollen season); ‐ Asthma symptoms + use of asthma rescue medication (entire pollen season); ‐ clinical benefit of SLIT (reduction of rhinoconjunctivitis symptoms and rhinitis symptom control); ‐ Mean improvement in allergic severity S in CPT (baseline and visit V4); ‐ changes of the threshold allergen concentration for a positive response within CPT (baseline and V4) ; ‐The redness of the eye in CPT (assessed by a central observer); ‐ The “well days”(entire pollen season, maximum symptom score of 2, no rescue medication) ; ‐ Assessment of grass specific IgG4; ‐ A global evaluation (entire pollen season); ‐ Safety (physical examinations, adverse Events, safety laboratory data) ; ‐ Rhinoconjunctivitis Quality of Life (RQLQ) Timepoint(s) of evaluation of this end point: The peak of the grass pollen season, defined by those 30 consecutive days per centre with the highest local grass pollen counts, starting with at least “moderate” pollen concentrations (stage 2 according to Deutscher Wetterdienst Medizin‐Meteorologie, http://www.dwd.de) in the nearest pollen count station in that region; INCLUSION CRITERIA: • Female or male patients aged 18–75 years with a history of at least two years of grass pollen induced allergic rhinitis and/or allergic rhinoconjunctivitis with or without seasonal controlled allergic asthma [From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2012. Available from: http://www.ginasthma.org]. • Clinical sensitization to grass pollen. Patients with sensitization to perennial allergens like mites, cats and dogs may be included, in the case that these sensitizations are not clinically relevant during the evaluation season. • Positive clinical history of grass pollen, proven by: ‐ the majority of clinical symptoms appearing during the appropriate season for grass, ‐ specific IgE reactivity to grass pollen: CAP‐RAST results to Phl p1 or Phl p5b = class 2 (0.70 kU/L) AND CAP‐RAST results to Phl p1 or Phl p5b > CAP‐RAST results Phl p7 or Phl p12 ‐ positive screening skin prick