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

Primary Purpose

Hay Fever

Status

Unknown status

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Placebo solution

gpASIT+TM

About this trial

This is an interventional treatment trial for Hay Fever

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Allergy diagnosis:
A clinical history of moderate to severe grass pollen-induced Seasonal Allergic Rhinoconjunctivitis (SARC) for at least 2 pollen seasons, requiring treatment with either antihistamines or nasal corticosteroids during the 2017 and 2018 grass pollen seasons and with symptoms interfering with usual daily activities or with sleep, as defined according to Allergic Rhinitis and its Impact on Asthma (ARIA) classification of rhinitis (Bousquet et al. 2001)
A positive Skin Prick Test (SPT) (wheal diameter ≥3 mm) to grass pollen mixture, histamine wheal ≥3 mm, sodium chloride (NaCl) control reaction <2 mm AND
Specific IgE against grass pollen ≥0.7 kU/L. 6)
For asthmatic patients, confirmed diagnosis of controlled asthma according to Global Initiative for Asthma (GINA; 2018)

Exclusion Criteria:

Diagnosis of mastocytosis;
Previous (within the last 5 years) immunotherapy with grass allergens;
Ongoing immunotherapy with grass allergens or any other allergens;
Patients with any history of anaphylaxis due to any cause;
Patients with a history of hypersensitivity to the excipients of the investigational product;
Patients with a forced expiratory volume in 1 second (FEV1) <80% of the predicted value (European Community for Steel and Coal) or with a peak expiratory flow (PEF) <70% of the individual optimum value at the Screening visit;
History of being intubated with mechanical ventilator support or in intensive care unit for asthma at any point in the patient's life;
History of emergency visit or hospital admission for asthma in the previous 12 months;
Clinical history of moderate to severe allergic rhinitis, as defined according to the ARIA classification of rhinitis, due to tree pollen near or overlapping the grass pollen season;
Clinical history of moderate to severe allergic rhinitis as defined according to the ARIA classification of rhinitis caused by an allergen to which the participant is regularly exposed;

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo solution

gpASIT+™ (Grass Pollen-ASIT+™)

Arm Description

Placebo Comparator: Placebo The product will be supplied as ready-to-use vials containing 1.5 mL of aqueous buffered solutions at pH 7.4 containing sodium phosphate, NaCl, mannitol and trehalose. the dosage is100 µg/ml. The treatment schedule will consist in a subcutaneous injection over four visits during 3 consecutive weeks. The patient will receive two injections (1 per arm)with an interval of 30 minutes between both.

Experimental: gpASIT+™ The product will be supplied as ready-to-use vials containing 1.5 mL of aqueous buffered solutions at pH 7.4 with a grass pollen peptide concentration of 100 µg/mL. Excipients are sodium phosphate, NaCl, mannitol and trehalose. the dosage is100 µg/ml.The treatment schedule will consist in a subcutaneous injection over four visits during 3 consecutive weeks.The patient will receive two injections (1 per arm)with an interval of 30 minutes between both.

Outcomes

Primary Outcome Measures

Average daily Combined Symptom and Medication Score collected during the peak of the grass pollen season

Symptoms are measured on a scale from 0 to 3- No symptoms= 0 mild symptoms=1 moderate symptoms =2 severe symptoms =3. Daily symptom score is calculated as: daily RTSS/6. Medication score: No rescue medications used =0 Tablet of antihistamine = 1 Nasal spray of fluticasone propionate with or without antihistamine= 2 Tablet of methylprednisolone with or without antihistamine/ fluticasone propionate= 3 Maximum daily Rescue Medication Score (RMS):3 CSMS= dSS (daily symptom score) (0-3) + dMS (daily medication score)(0-3)= 0-6 The daily symptom score and the daily RMS each range from 0 to 3 and, thus, the daily CSMS ranges from 0 to 6. The average CSMS of the peak of the grass pollen season or the whole grass pollen season will be calculated, per patient, as the sum of the daily CSMS within the peak of pollen season or the whole pollen season divided by the number of days of the peak pollen season or the whole pollen season, respectively (as defined by Pfaar et al. 2014).

Secondary Outcome Measures

Combined symptom and medication score (CSMS) over the entire grass pollen season

Symptom subscores (eyes and nose) over the peak period and the entire grass pollen season

Symptom scores for nose (rhinorrhoea, sneezing, nasal pruritus, nasal congestion) and eye (ocular pruritus, watery eyes) symptoms will be collected on a daily basis, using a four-point ordinal scale. Nasal symptoms: (Score 0-3) 0 = no symptoms = mild symptoms (sign/symptom clearly present, but minimal awareness; easily tolerated) = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable) = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping) Itchy nose:0-3 Sneezing:0-3 Runny nose:0-3 Blocked nose:0-3 Conjunctival symptoms: Itchy/red eyes:0-3 Watery eyes:0-3

Total Symptom Score (TSS: the sum of the eyes, nose and lung symptom scores) in asthmatic patients only over the peak period and the entire grass pollen season

The daily Rhinoconjunctivitis Total Symptom Score (RTSS) will correspond to the sum of the six nose and eye symptoms (score ranging from 0 to 18). Then, daily symptom score is calculated as: daily RTSS/6.The common rating system is the following: 0 = no symptoms; 1 = mild symptoms (sign/symptom clearly present but minimal awareness, easily tolerated); 2 = moderate symptoms (definite awareness of any sign/symptom that is bothersome but tolerated); 3 = severe symptoms (sign/symptom that is hard to tolerate, causing interference with activities of daily living and/or sleeping) as defined by Pfaar et al. 2014

Use of rescue medication to relieve asthma symptoms in asthmatic patients

Patients will be instructed to use the rescue medications according to the following standardised and stepwise procedure: 1. In first instance: oral H1 antihistamine (desloratadine, one 5 mg tablet/day); 2. If Step 1 fails or is insufficient, intranasal corticosteroid: fluticasone propionate (50 µg/dose, one puff/nostril as needed) (alone or combined with oral antihistamine); 3. If Step 2 fails: oral corticosteroid (methylprednisolone 16 mg tablet, one tablet/day for a maximum of 3 days).

Number (%) of "well days"

A "well day" is a day for which the patient does not report any intake of any rescue medication ( RMS = 0) and with no Grade ≥2 individual eye or nose symptom and overall Rhinoconjunctivitis Total Symptom Score (RTSS) ≤2.

Standardised Rhinoconjunctivitis Quality of Life Questionnaire in all patients

to measure the functional impairments of the patients resulting from their rhinoconjunctivitis in their day-to-day life (Juniper et al. 1999)-The validated RQLQ has 28 questions in 7 domains (activity limitation, sleep problems, nose symptoms, eye symptoms, non-nose/eye symptoms, practical problems and emotional function). There are 3 'patient-specific' questions in the activity domain which allow patients to select 3 activities in which they are most limited by their rhinoconjunctivitis. Patients recall how bothered they have been by their rhinoconjunctivitis during the previous week and to respond to each question on a 7-point scale (0 = not impaired at all - 6 = severely impaired). The overall RQLQ score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains.

Patient's Global Efficacy (PGE) assessment.

At the end of the study, the patients will be asked how they have felt overall during the study grass pollen season compared to previous grass pollen seasons ("much better", "better", "the same", "worse", "much worse"

Number of working days lost due to grass pollen-induced allergy symptoms

Absenteeism, evaluated by recording the number of working days lost due to grass pollen-induced allergic rhinoconjunctivitis

Systemic allergic reactions <30 minutes after investigational product administration

Immediate and delayed systemic reactions will be graded according to the World Allergy Organisation classification (Cox et al. 2010).

Local reactions at the injection site (swelling and redness) after investigational product administration

local reaction (wheal diameter) is 5 to 8 cm

Other treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

A TEAE is defined as an event that emerges during treatment having been absent pre-treatment, or which worsens relative to the pre-treatment state.Adverse Events will be tabulated by System Organ Class (SOC) and Preferred Term (PT) after medical coding using MedDRA

Induction of grass pollen-specific Immunoglobulin: IgE, IgG and IgG4 in serum of all patients

In all patients at all sites, 2 mL of blood will be withdrawn for the measurement of grass pollen-specific IgE, IgG4 and IgG in serum sites. Grass pollen-specific IgE, IgG and IgG4 measurements in patient serum will be assessed by ImmunoCAP® method in a central laboratory

Full Information

NCT ID

NCT03724240

First Posted

October 16, 2018

Last Updated

October 26, 2018

Sponsor

ASIT Biotech S.A.

1. Study Identification

Unique Protocol Identification Number

NCT03724240

Brief Title

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

Official Title

A Multicentre, International, Randomised, Double-blind, Placebo-controlled Study to Demonstrate the Clinical Efficacy and Safety of Subcutaneous Immunotherapy With gpASIT+™ in Patients With Grass Pollen-induced Allergic Rhinoconjunctivitis

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Unknown status

Study Start Date

January 2, 2019 (Anticipated)

Primary Completion Date

September 2019 (Anticipated)

Study Completion Date

December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ASIT Biotech S.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a randomised, double-blind, placebo-controlled, international, multicentre, confirmatory Phase III study in patients with grass pollen-related allergic rhinoconjunctivitis. After having given written informed consent, the patients will be examined to establish eligibility according to inclusion/exclusion criteria. The eligible patients will be randomised to Placebo or gpASIT+™ treatment according to a 1:1 ratio. Study treatment will be administered before the start of the pollen season in 2019

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hay Fever

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Double blind

Allocation

Randomized

Enrollment

624 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo solution

Arm Type

Placebo Comparator

Arm Description

Arm Title

gpASIT+™ (Grass Pollen-ASIT+™)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Placebo solution

Intervention Description

4 x 2 injection over 21 days the dosage is100 µg/ml

Intervention Type

Biological

Intervention Name(s)

gpASIT+TM

Intervention Description

4 x 2 injection over 21 days the dosage is100 µg/ml

Primary Outcome Measure Information:

Title

Average daily Combined Symptom and Medication Score collected during the peak of the grass pollen season

Description

Time Frame