Clinical trial NCT02560948: Clinical Efficacy and Safety of a Subcutaneous Immunotherapy With gpASIT+™ in Patients With Grass Pollen-induced Allergic Rhinoconjunctivitis
Official title: A Multicenter, International, Randomised, Double-blind, Placebo Controlled Study to Demonstrate the Clinical Efficacy and Safety of a Subcutaneous Immunotherapy With gpASIT+™ in Patients With Grass Pollen-induced Allergic Rhinoconjunctivitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hay Fever
Lead sponsor: BioTech Tools S.A.
Sponsor class: INDUSTRY
First posted: 2015-09-25
Enrollment: 554
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: gpASIT+TM product is based on highly purified allergen fragments obtained from grass pollen. The purpose of this study is to demonstrate the clinical efficacy and safety of a subcutaneous immunotherapy with gpASIT+™ in patients with grass pollen-induced allergic rhinoconjunctivitis compared to placebo.


Eligibility criteria: Key Inclusion Criteria:

* Allergy diagnosis:

  * A medical history of moderate to severe seasonal allergic rhinoconjunctivitis (SARC) for the grass pollen season during at least the two previous seasons (definition of allergy severity according to ARIA (Bousquet et al 2001))
  * A positive skin prick test (SPT - wheal diameter ≥ 3 mm) to grass pollen mixture, histamine wheal ≥ 3 mm, NaCl control reaction \< 2 mm
  * Specific IgE against grass pollen (with recombinant allergens - g213) \> 0.7 kU/L
  * Positive response to CPT with at least 10,000 SQ-E/mL of grass allergens
* Patients treated with anti-allergic medication for at least 2 grass pollen seasons prior to enrollment
* For asthmatic patients: confirmed diagnosis of controlled asthma according to Global Initiative for Asthma (GINA) guidelines (steps 1-3, GINA 2014)

Key Exclusion Criteria:

* Previous immunotherapy with grass allergens within the last 5 years
* Ongoing immunotherapy with grass allergens or any other allergens
* Patients with a history of anaphylaxis, including food (e.g. peanut or marine animals) or hymenoptera venom (e.g. bee or wasp stings) or medication (e.g. penicillin)
* Patients with partly controlled or uncontrolled asthma according to GINA guidelines (GINA 2014)
* Patients with chronic asthma or emphysema, particularly with a forced expiratory volume in 1 second (FEV1) \< 80% of the predicted value (ECSC) or with a peak expiratory flow (PEF) \< 70% of the individual optimum value
* Patients symptomatic to inhaled allergens circulating during the grass pollen season (specific to each country: e.g. birch, hazel, mugwort, ragweed, olive, Alternaria alternata)
* Patients symptomatic to perennial inhaled allergens (house dust mites, cat, dog) to which the patients are regularly exposed

Primary outcomes:
measure: Combined Symptom and Medication Score (CSMS)
timeFrame: over the peak (corresponding to 14 consecutive days with highest pollen counts) of grass pollen season estimated between 3 and 6 months after treatment
Secondary outcomes:
measure: Combined Symptom and Medication Score (CSMS)
timeFrame: over the entire grass pollen season estimated between 3 and 6 months after treatment
measure: Symptom sub-scores (Eyes, Nose)
timeFrame: over the peak period (14 consecutive days with highest pollen counts within grass pollen season) and over the pollen season estimated between 3 and 6 months after treatment
measure: Well days: number of days with symptomatic score below or equal to 2 and no rescue medication
timeFrame: over the peak period (14 consecutive days with highest pollen counts within grass pollen season) and over the pollen season estimated between 3 and 6 months after treatment
measure: Lung Symptom Score (LLS: the average of coughing, wheezing, chest tightness and exercise induced dyspnoea scores) in asthmatic patients
timeFrame: over the peak period (14 consecutive days with highest pollen counts within grass pollen season) and over the pollen season estimated between 3 and 6 months after treatment
measure: Total Symptom Score (TSS: the sum of the nose, eye and lung scores) in asthmatic patients
timeFrame: over the peak period (14 consecutive days with highest pollen counts within grass pollen season) and the pollen season estimated between 3 and 6 months after treatment
measure: Use of rescue medication to relief asthma symptoms in asthmatic patients
timeFrame: over the peak period (14 consecutive days with highest pollen counts within grass pollen season) and the pollen season estimated between 3 and 6 months after treatment
measure: Conjunctival Provocation Test (CPT) outcomes
timeFrame: at baseline and up to 6 weeks
measure: Standardized Quality-of-Life Questionnaires for asthma and rhinoconjunctivitis
timeFrame: between 2 weeks and 8 months after treatment
measure: Number of working day lost due to grass pollen induced-allergy symptoms
timeFrame: between 2 weeks and 8 months after treatment
measure: Loss of productivity at work due to grass pollen induced-allergy symptoms, using a visual analog scale (VAS)
timeFrame: between 2 weeks and 8 months after treatment
measure: Solicited adverse events
timeFrame: up to 4 weeks
measure: Unsolicited adverse events and serious adverse events
timeFrame: up to 8 months
measure: Physical examinations and vital signs
timeFrame: up to 8 months
measure: Laboratory investigations (haematology, clinical biochemistry, immunological parameters)
timeFrame: up to 8 months
measure: Use of rescue medication
timeFrame: up to 4 weeks
Other outcomes:
measure: Production of grass pollen specific immunoglobulins IgE, IgG and IgG4
timeFrame: up to 8 months
measure: Production of blocking antibodies (FAB assay)
timeFrame: up to 8 months
measure: Reduction of Th2 response by measuring IL-4+ and IFN-gamma+ production
timeFrame: up to 8 months
measure: Induction of regulatory T cells (Treg)
timeFrame: up to 8 months
measure: Induction of regulatory B cells (Breg) and their phenotyping
timeFrame: up to 8 months
measure: Reduction of basophil activation measured through detection of CD63 expression marker on activated cells
timeFrame: up to 8 months
Locations:
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Milano
country: Italy
facility: Clinica dell'Azienda Opsedaliera Luigi Sacco
city: Madrid
country: Spain
facility: Fundacion Jiménez Diaz
Study officials:
affiliation: Private practice, Aachen, Germany
name: Ralph Mösges, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: UZ Gent, Gent, Belgium
name: Claus Bachert, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Pilsen, Pilsen, Czech Republic
name: Petr Panzner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU de Strasbourg, Strasbourg, France
name: Frédéric de Blay, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinica dell'Azienda Ospedaliera Luigi Sacco Di Milano, Milano, Italy
name: Enrico Iemoli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundación Jiménez Díaz, Madrid,Spain
name: Joachin Sastre, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sharif H, Singh I, Kouser L, Mosges R, Bonny MA, Karamani A, Parkin RV, Bovy N, Kishore U, Robb A, Katotomichelakis M, Holtappels G, Derycke L, Corazza F, von Frenckell R, Wathelet N, Duchateau J, Legon T, Pirotton S, Durham SR, Bachert C, Shamji MH. Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: A randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2019 Sep;144(3):738-749. doi: 10.1016/j.jaci.2019.02.023. Epub 2019 Mar 5.