Grass Pollen Allergen Immunotherapy Tablet (AIT) Time Course Study

NCT02005627 | Completed Phase 2 Results

• 3 other identifiers: 13IC08472013-003732-7213/EM/0351
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

About 45 million people in Europe have allergic rhinitis (hay fever) - inflammation of the nasal passages causing sneezing, runny nose, nasal congestion, itching and tearing of the eyes. In the United Kingdom (UK), seasonal hay fever due to grass pollen allergy accounts for approximately 7 times more doctors' appointments than asthma. The standard treatment for hay fever consists of treating the symptoms with a nasal spray and an antihistamine. However, in a survey taken in a UK general practice less than 40% of patients with hay fever reported good symptom control with this standard treatment. For those patients with hay fever whose symptoms are not well controlled by treatment with antihistamines and nasal sprays, subcutaneous immunotherapy (SCIT) - (monthly injections of a grass allergen extract for a period of 3-5 years) is an effective alternative, and is approved in the UK on a named patient basis. More recently, allergen immunotherapy tablets (AITs) have been developed, including grass pollen allergen tablets. These have been shown to be highly effective in the treatment of hay fever, with the additional benefit of being convenient for patients, given that they may be taken at home. Grazax® (manufactured by Allergologisk Laboratorium København (ALK)-Abello, Denmark) has UK and European Union (EU) license for use in the treatment of troublesome grass pollen induced hay fever. The aim of this research is to investigate the effects of the AIT treatment on the immune system over time - which changes are taking place and when in the course of treatment. This will provide insight into the complexities of the development of allergen-specific immune tolerance - how harmful allergic responses against innocuous substances such as grass pollen can be overridden.

Conditions

Allergic Rhinitis

Keywords

grass pollen allergy; hayfever; atopy; allergic rhinitis; sublingual immunotherapy tablets

Outcome Measures

Primary Outcomes (1)

• Total Nasal Symptom Score After Nasal Allergen Challenge (NAC)

  The total nasal symptom score at one hour after grass pollen nasal allergen challenge in active versus placebo treated participants after treatment period. Score ranges from minimum 0 point to maximum of 12 points. Higher score is more severe symptoms.

  60 minutes post-challenge after 12 months of treatment

Secondary Outcomes (4)

• Early Phase Intradermal Test

  after 12 months of treatment

• Late Phase Intradermal Test

  after 12 months of treatment

• Change From Baseline in Delta Peak Nasal Inspiratory Flow in L/Min

  60 minutes post-challenge after 12 months of treatment

• End of Season Global Rhinitis Symptoms

  after treatment at 12 months

Study Arms (2)

Grazax

ACTIVE COMPARATOR

The active treatment arm will receive active grass pollen immunotherapy tablet (AIT), Grazax Oral Lyophilisate 75,000 standardised quality units tablet (SQ-T) once daily.

Drug: Grazax

Grazax Placebo

PLACEBO COMPARATOR

This arm will receive Grazax placebo once daily which contains the same composition as in the active Grazax tablet with the only difference being the exclusion of the grass pollen allergen extract.

Drug: Grazax Placebo

Interventions

Grazax DRUG

The active treatment arm will receive active grass pollen immunotherapy tablet (AIT), Grazax Oral Lyophilisate 75,000 SQ-T once daily.

Also known as: Grazax 75,000 SQ-T oral lyophilisate, Allergen Immunotherapy Tablet, SQ Standardized Grass Allergy Immunotherapy

Grazax

Grazax Placebo DRUG

This arm will receive Grazax placebo once daily which contains the same composition as in the active Grazax tablet with the only difference being the exclusion of the grass pollen allergen extract.

Also known as: Grazax Placebo tablet

Grazax Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age 18 to 65
• grass pollen-induced allergic rhinoconjunctivitis for at least 2 years with peak symptoms in May-July.
• moderate to severe rhinoconjunctivitis symptoms with or without mild seasonal asthma interfering with usual daily activities/sleep.
• rhinoconjunctivitis that remains troublesome despite treatment with either antihistamines or nasal corticosteroids during the grass pollen season.
• Positive skin prick test response (wheal diameter ≥ 3 mm) to timothy grass pollen.
• Positive specific immunoglobulin E (IgE), defined as IgE immunoCAP ≥ 0.7 Immuno Solid Phase Allergenchip (ISAC) standardized units (ISU), against timothy grass pollen.
• if applicable a negative urine pregnancy test and willingness to use an effective form of contraception for the duration of involvement in the study.
• The ability to give informed consent and comply with study procedures.
• A positive grass pollen nasal allergen challenge test as defined by a total nasal symptom score (TNSS) of at least 7/12 after 5 minutes with an allergen dose of 5,000 bioequivalent units (BU)/ml.

You may not qualify if:

• Previous grass pollen allergen immunotherapy.
• Prebronchodilator forced expiratory volume at one second (FEV1) \< 70% of predicted value out of grass-pollen season.
• A clinical history of symptomatic allergic rhinitis and/or asthma caused by an allergen to which the participant is regularly exposed.
• Perennial asthma requiring regular inhaled corticosteroids.
• Seasonal symptoms outside the grass-pollen season.
• History of emergency visit or hospital admission for asthma in the previous 12 months.
• History of chronic obstructive pulmonary disease.
• History of significant recurrent acute sinusitis.
• History of chronic sinusitis.
• At screening visit evidence for upper respiratory tract infection.Participants may be re-evaluated for eligibility after symptoms resolve.
• Current smokers or a history of ≥ 5 pack years.
• History of life-threatening anaphylaxis or angioedema.
• Ongoing systemic immunosuppressive treatment.
• The use of any investigational drug within 30 days of the screening visit.
• The presence of any medical condition that the investigator deems incompatible with participation in the study.

Sponsors & Collaborators

• Imperial College London: lead
• King's College London: collaborator
• ALK-Abelló A/S: collaborator
• Wellcome Trust: collaborator

Study Sites (1)

NHS Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Related Publications (1)

• Steveling EH, Lao-Araya M, Koulias C, Scadding G, Eifan A, James LK, Dumitru A, Penagos M, Calderon M, Andersen PS, Shamji M, Durham SR. Protocol for a randomised, double-blind, placebo-controlled study of grass allergen immunotherapy tablet for seasonal allergic rhinitis: time course of nasal, cutaneous and immunological outcomes. Clin Transl Allergy. 2015 Dec 17;5:43. doi: 10.1186/s13601-015-0087-2. eCollection 2015.

  PMID: 26682038 RESULT

MeSH Terms

Conditions

Rhinitis, Allergic; Rhinitis, Allergic, Seasonal

Interventions

Grazax; Desensitization, Immunologic

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Results Point of Contact

• Title: Stephen R Durham
• Organization: Imperial College London

s.durham@imperial.ac.uk

+44207-351-8024

Study Officials

• Stephen R Durham, Prof.

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2013
• First Posted: December 9, 2013
• Study Start: September 1, 2013
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: December 4, 2019
• Results First Posted: December 4, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)