Safety and Tolerability of ToleroMune Grass in Grass Allergic Subjects With Rhinoconjunctivitis

Study Overview
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Brief Summary
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Grass pollen allergens are universally recognised as a major cause of allergic diseases in humans and animals, including asthma, allergic rhinitis, conjunctivitis and dermatitis. Worldwide, at least 40% of allergic patients are sensitized to grass pollen allergens and between 50-90% of hayfever or seasonal allergy sufferers are allergic to grass pollen. ToleroMune Grass is a novel, synthetic, allergen-derived peptide desensitising vaccine, currently being developed for the treatment of grass allergy. The purpose of the present study is to evaluate the safety and tolerability of multiple ascending doses of ToleroMune Grass in subjects allergic to grass.

Detailed Description
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This study is designed as a randomised, double-blind, placebo-controlled study to evaluate the safety and tolerability of escalating multiple doses of ToleroMune Grass in subjects with a documented history of allergic rhinoconjunctivitis on exposure to grass. The efficacy of ToleroMune HDM will also be explored LPSR, EPSR, CPT and levels of grass specific IgE. The study will consist of 3 study periods. In Period 1, Screening will be performed up to a maximum of 6 weeks before randomisation. Period 2 (Treatment Period) will consist of 4 visits (Visits 3A-3D) four weeks apart. The first cohort will receive the lowest dose and successive dose groups will increasing doses of ToleroMune Grass, provided the first administration of the previous dose was safe and well tolerated. In Period 3, 2 Post-treatment Challenge visits will take place, the first will be 2 weeks after the last administration in the Treatment Period and the second will be 17 weeks after the first administration. Follow-up will be conducted 3-10 days after the second PTC.

Official Title
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An Escalating, Multiple-dose Study in Grass Allergic Subjects to Assess the Safety of Intradermal Injection of ToleroMune Grass

Conditions
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Allergy

Intervention / Treatment
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* Biological: Placebo
* Biological: ToleroMune Grass


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18-65 years Minimum 2 year history of rhinoconjunctivitis on exposure to grass Positive skin prick test to whole grass allergen LPSR to whole grass allergen 8-10 hours after intradermal injection of greater than 35mm diameter response Positive CPT to whole grass allergen with a score ≥4 Exclusion Criteria: Subjects with a history of asthma Subjects with an FEV1 <80% of predicted Subjects with a rye grass specific IgE >100 kU/L Subjects with an acute phase skin response to whole grass allergen with a mean wheal diameter > 50 mm Subjects who score >1 for redness of conjunctiva or who have any watering or itchiness in the eye before administration of the CPT Treatment with beta-blockers, alpha-adrenoreceptor blockers, tranquillisers or psychoactive drugs History of any significant disease or disorder (e.g. cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Subjects to receive either active or placebo | Biological: Placebo<br>* Solution resembling active solution but without peptides<br>Biological: ToleroMune Grass<br>* 1 x4 administrations 4 weeks apart<br>|
| Experimental: Cohort 2<br>Subjects to receive either active or placebo comparator | Biological: Placebo<br>* Solution resembling active solution but without peptides<br>Biological: ToleroMune Grass<br>* 1 x4 administrations 4 weeks apart<br>|
| Experimental: Cohort 3<br>Subjects to receive either active or placebo comparator | Biological: Placebo<br>* Solution resembling active solution but without peptides<br>Biological: ToleroMune Grass<br>* 1 x4 administrations 4 weeks apart<br>|
| Experimental: Cohort 4<br>Subjects to receive either active or placebo comparator | Biological: Placebo<br>* Solution resembling active solution but without peptides<br>Biological: ToleroMune Grass<br>* 1 x4 administrations 4 weeks apart<br>|
| Experimental: Cohort 5<br>Subjects to receive either active or placebo comparator | Biological: Placebo<br>* Solution resembling active solution but without peptides<br>Biological: ToleroMune Grass<br>* 1 x4 administrations 4 weeks apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of multiple intradermal injections of ToleroMune Grass in grass allergic subjects with allergic rhinoconjunctivitis |  | Upto 22 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area of Late Phase Skin Response |  | Baseline and 14 weeks | 
| Area of Early Phase Skin Response |  | Baseline and 14 weeks | 
| Change in CPT score |  | Baseline and 4 weeks | 
| Grass specific IgG4 |  | Baseline and 14 weeks | 
| Change in CPT score |  | Baseline and 14 weeks | 
| Area of Early Phase Skin Response |  | Baseline and 17 weeks | 
| Grass specific IgE |  | Baseline and 17 weeks | 
| Area of Late Phase Skin Response |  | Baseline and 17 weeks | 
| Change in CPT score |  | 17 weeks after start of treatment | 
| Change in CPT score |  | Baseline and 8 weeks | 
| Change in CPT score |  | Baseline and 12 weeks | 
| Grass specific IgE |  | Baseline and 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Grass Allergy, Immunotherapy, Rhinoconjunctivitis, ToleroMune Grass