Clinical Efficacy and Safety of a Subcutaneous Immunotherapy With gpASIT+™ in Patients With Grass Pollen-induced Allergic Rhinoconjunctivitis

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

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.

Study Overview

• Status: Completed
• Conditions: Hay Fever
• Intervention / Treatment: Biological: Placebo solution; Biological: gpASIT+TM

• Study Type: Interventional
• Enrollment (Actual): 554
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium
    • University Hospital Ghent
• Italy
  • Milano, Italy
    • Clinica dell'Azienda Opsedaliera Luigi Sacco
• Spain
  • Madrid, Spain
    • Fundación Jiménez Díaz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo solution; 4 x 2 injections over 21 days
Experimental: gpASIT+TM	Biological: gpASIT+TM; 4 x 2 injections over 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Combined Symptom and Medication Score (CSMS)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined Symptom and Medication Score (CSMS)		over the entire grass pollen season estimated between 3 and 6 months after treatment
Symptom sub-scores (Eyes, Nose)		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
Well days: number of days with symptomatic score below or equal to 2 and no rescue medication		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
Lung Symptom Score (LLS: the average of coughing, wheezing, chest tightness and exercise induced dyspnoea scores) in asthmatic patients		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
Total Symptom Score (TSS: the sum of the nose, eye and lung scores) in asthmatic patients		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
Use of rescue medication to relief asthma symptoms in asthmatic patients		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
Conjunctival Provocation Test (CPT) outcomes		at baseline and up to 6 weeks
Standardized Quality-of-Life Questionnaires for asthma and rhinoconjunctivitis		between 2 weeks and 8 months after treatment
Number of working day lost due to grass pollen induced-allergy symptoms		between 2 weeks and 8 months after treatment
Loss of productivity at work due to grass pollen induced-allergy symptoms, using a visual analog scale (VAS)		between 2 weeks and 8 months after treatment
Solicited adverse events	Local reactions at the injection site (swelling and redness); Allergic systemic reactions	up to 4 weeks
Unsolicited adverse events and serious adverse events		up to 8 months
Physical examinations and vital signs		up to 8 months
Laboratory investigations (haematology, clinical biochemistry, immunological parameters)		up to 8 months
Use of rescue medication		up to 4 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Production of grass pollen specific immunoglobulins IgE, IgG and IgG4	up to 8 months
Production of blocking antibodies (FAB assay)	up to 8 months
Reduction of Th2 response by measuring IL-4+ and IFN-gamma+ production	up to 8 months
Induction of regulatory T cells (Treg)	up to 8 months
Induction of regulatory B cells (Breg) and their phenotyping	up to 8 months
Reduction of basophil activation measured through detection of CD63 expression marker on activated cells	up to 8 months

Collaborators and Investigators

• Sponsor: BioTech Tools S.A.
• Investigators: Principal Investigator: Ralph Mösges, Professor, Private practice, Aachen, Germany; Principal Investigator: Claus Bachert, Professor, UZ Gent, Gent, Belgium; Principal Investigator: Petr Panzner, MD, University Hospital of Pilsen, Pilsen, Czech Republic; Principal Investigator: Frédéric de Blay, Professor, CHRU de Strasbourg, Strasbourg, France; Principal Investigator: Enrico Iemoli, MD, Clinica dell'Azienda Ospedaliera Luigi Sacco Di Milano, Milano, Italy; Principal Investigator: Joachin Sastre, Professor, Fundación Jiménez Díaz, Madrid,Spain

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: September 23, 2015
• First Submitted That Met QC Criteria: September 24, 2015
• First Posted (Estimate): September 25, 2015

Study Record Updates

• Last Update Posted (Actual): October 11, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis, Allergic; Rhinitis; Rhinitis, Allergic, Seasonal
• Other Study ID Numbers: BTT-gpASIT009