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

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

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.

Study Overview

• Status: Completed
• Conditions: Allergy
• Intervention / Treatment: Biological: Placebo; Biological: ToleroMune Grass

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4M6
    • Centre de Recherche Appliqué en Allergie de Québec

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Circassia Limited
• Collaborators: Adiga Life Sciences, Inc.
• Investigators: Principal Investigator: Jacques Hebert, MD, Centre De Recherche Appliquée en Allergie De Québec

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: July 8, 2010
• First Submitted That Met QC Criteria: July 19, 2010
• First Posted (Estimate): July 20, 2010

Study Record Updates

• Last Update Posted (Estimate): May 20, 2011
• Last Update Submitted That Met QC Criteria: May 19, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Immunotherapy; Rhinoconjunctivitis; ToleroMune Grass; Grass Allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: TG001