Grass Pollen Allergen Immunotherapy Tablet (AIT) Time Course Study (Pollen+)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Imperial College London
Sponsor:
Collaborators:
King's College London
ALK-Abelló A/S
Wellcome Trust
Information provided by (Responsible Party):
Stephen Durham, Imperial College London
ClinicalTrials.gov Identifier:
NCT02005627
First received: December 4, 2013
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

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, 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 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.


Condition Intervention Phase
Allergic Rhinitis
Drug: Grazax
Drug: Grazax Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Randomised Placebo-controlled Study of Grass Pollen Allergen Immunotherapy Tablet (AIT) for Seasonal Rhinitis: Time Course of Nasal, Cutaneous and Immunological Outcomes

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Change from baseline early phase response (EPS) after nasal allergen challenge (NAC) [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: Yes ]
    The area under the curve (AUC) of the early phase response (total nasal symptom score, TNSS, 0-60 minutes) following grass pollen nasal allergen challenge in active versus placebo-treated atopic participants at 12 months.


Secondary Outcome Measures:
  • Change from baseline in early phase (EP) and late phase response (LPR) to intradermal grass pollen allergen [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: Yes ]
    Cross-sectional area in cm2 of EPR and LPR skin responses to intradermal grass pollen allergen injection at 12 months in active versus placebo treated participants.

  • Change from specific IgG4 level and inhibition of B cell IgE-facilitated allergen binding [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Serum and nasal fluid grass pollen specific IgG4 level and inhibition of B cell IgE-facilitated allergen binding in active versus placebo-treated atopic patients versus non-atopic controls at 12 months.

  • Change from blood Basophil activation [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Allergen-induced peripheral blood basophil activation in active versus placebo-treated atopic participants versus non-atopic controls at 12 months.


Other Outcome Measures:
  • Change from Combined symptom + medication score [ Time Frame: Baseline, 2, 3, 4, 6, 8 and 12 months ] [ Designated as safety issue: No ]
    Mean combined symptom + medication scores over the course of the 2014 grass pollen season in active versus placebo-treated participants.

  • Change from proportion of allergen-specific T reg cells [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Proportion of allergen-specific phenotypic Treg cells in peripheral blood as measured by flow cytometry in active vs placebo-treated atopic participants versus non-atopic controls at 12 months.


Estimated Enrollment: 44
Study Start Date: December 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Grazax
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
The active treatment arm will receive active grass pollen immunotherapy tablet (AIT), Grazax Oral Lyophilisate 75,000 SQ-T once daily.
Other Names:
  • Grazax 75,000 SQ-T oral lyophilisate
  • Allergen Immunotherapy Tablet
  • SQ Standardized Grass Allergy Immunotherapy
Placebo Comparator: Grazax Placebo
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
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.
Other Name: Grazax Placebo tablet

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Atopic Participants:

Inclusion Criteria:

  • 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 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.

Exclusion Criteria:

  • 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.
  • History of fish allergy with positive skin test and/or positive specific IgE test to vertebrate/finned fish.
  • Contraindications taking Grazax.

Non-Atopic:

Inclusion Criteria:

  • age 18 to 65.
  • Negative skin prick test response to timothy grass pollen and panel of aeroallergens.
  • Negative specific IgE, defined as IgE immunoCAP < 0.35 ISU, against timothy grass pollen.
  • If applicable a negative urine pregnancy test at the time of screening 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.

Exclusion criteria:

  • Previous grass pollen allergen immunotherapy.
  • Prebronchodilator FEV1 < 70% of predicted value out of grass-pollen season.
  • symptomatic allergic rhinitis and/or asthma caused by an allergen to which the participant is regularly and perennially exposed (e.g. cat dander).
  • Perennial asthma requiring regular inhaled corticosteroids.
  • Seasonal symptoms outside or during 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, current symptoms of 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02005627

Contacts
Contact: Esther H Steveling, MD 07872850275 e.steveling@imperial.ac.uk
Contact: Alina F Dumitru, MD, PhD 07872850275 a.dumitru@imperial.ac.uk

Locations
United Kingdom
NHS Royal Brompton Hospital Recruiting
London, United Kingdom, SW3 6NP
Contact: Esther H Steveling, MD    07872850275    e.steveling@imperial.ac.uk   
Contact: Alina F Dumitru, MD, PhD    07872850275    a.dumitru@imperial.ac.uk   
Principal Investigator: Stephen R Durham, MD, MA, FRCP         
Sub-Investigator: Moises Calderon, MD PhD         
Sub-Investigator: Mohamed Shamji, PhD         
Sub-Investigator: Esther H Steveling, MD         
Sub-Investigator: Mongkol Lao-araya, MD         
Sub-Investigator: Guy Scadding, MBBS, MRCP         
Sub-Investigator: Aarif Eifan, MD         
Sub-Investigator: Alina F Dumitru, MD, PhD         
Sub-Investigator: Martin Penagos, MD, MSc         
Sponsors and Collaborators
Imperial College London
King's College London
ALK-Abelló A/S
Wellcome Trust
Investigators
Principal Investigator: Stephen R Durham, Prof. Imperial College London
  More Information

No publications provided

Responsible Party: Stephen Durham, Professor of Allergy and Respiratory medicine, Imperial College London
ClinicalTrials.gov Identifier: NCT02005627     History of Changes
Other Study ID Numbers: 13IC0847, 2013-003732-72, 13/EM/0351
Study First Received: December 4, 2013
Last Updated: January 7, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Imperial College London:
grass pollen allergy
hayfever
atopy
allergic rhinitis
sublingual immunotherapy tablets

Additional relevant MeSH terms:
Rhinitis
Rhinitis, Allergic, Perennial
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on August 20, 2014