Long-Term Effects of Sublingual Grass Therapy

NCT ID: NCT01335139

Last Updated: 2017-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2015-02-28

Brief Summary

The purpose of this research study is to investigate whether sublingual immunotherapy (SLIT, grass pollen tablets under the tongue) has long term effects in severe hay fever.

Detailed Description

This is a randomized, double-blind, single-center, placebo-controlled, three-arm study comparing SLIT with placebo and SCIT with placebo. The main comparison will be between SLIT and placebo.

Individuals with severe grass pollen hay fever, with or without associated seasonal asthma, will be recruited during the pollen season of March through September 2011. Eligible participants will be randomized to one of the following three treatment arms administered in a double-blind (masked), double-dummy fashion in a 1:1:1 ratio:

• SLIT + SCIT placebo
• SCIT + SLIT placebo
• SLIT placebo + SCIT placebo

Participants will receive treatment over a 2-year period followed by a 1-year blinded (masked) withdrawal phase. Participants will be provided with anti-allergic rescue medications (antihistamine, topical intranasal corticosteroids, and short-acting beta agonists) throughout the study. Clinical endpoint assessments will be performed at prior to initiating their assigned treatment, after 1 and 2 years of treatment, and after the 1-year withdrawal period at 3 years.

Conditions

Rhinitis, Allergic, Seasonal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

SCIT + Placebo

Subcutaneous immunotherapy (SCIT) + sublingual immunotherapy (SLIT) placebo

Group Type: EXPERIMENTAL

Subcutaneous immunotherapy (SCIT)

Intervention Type: BIOLOGICAL

Participants randomized to receive subcutaneous injection immunotherapy with placebo tablets. Subcutaneous immunotherapy was included as a positive control.

Placebo

Intervention Type: OTHER

Participants randomized to double-placebo tablets and injections. This group was included as a negative control.

SLIT + Placebo

Sublingual immunotherapy (SLIT) + subcutaneous immunotherapy (SCIT) placebo

Group Type: EXPERIMENTAL

Sublingual immunotherapy (SLIT)

Intervention Type: BIOLOGICAL

Participants randomized to receive sublingual allergen tablet immunotherapy with placebo injections.

Placebo

Intervention Type: OTHER

Participants randomized to double-placebo tablets and injections. This group was included as a negative control.

Placebo + Placebo

Sublingual immunotherapy (SLIT) placebo + subcutaneous immunotherapy (SCIT) placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Participants randomized to double-placebo tablets and injections. This group was included as a negative control.

Interventions

Sublingual immunotherapy (SLIT)

Participants randomized to receive sublingual allergen tablet immunotherapy with placebo injections.

Intervention Type: BIOLOGICAL

Subcutaneous immunotherapy (SCIT)

Participants randomized to receive subcutaneous injection immunotherapy with placebo tablets. Subcutaneous immunotherapy was included as a positive control.

Intervention Type: BIOLOGICAL

Placebo

Participants randomized to double-placebo tablets and injections. This group was included as a negative control.

Intervention Type: OTHER

Other Intervention Names

Grazax®; Alutard SQ Grass Pollen®

Eligibility Criteria

Inclusion Criteria

• A clinical history of grass pollen-induced allergic rhinoconjunctivitis for at least 2 years with peak symptoms in May, June, or July;
• A clinical history of moderate to severe rhinoconjunctivitis symptoms interfering with usual daily activities or with sleep as defined according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification of rhinitis;
• A clinical history of rhinoconjunctivitis for at least 2 years requiring treatment with either antihistamines or nasal corticosteroids during the grass pollen season;
• Positive skin prick test response, defined as wheal diameter greater than or equal to 3 mm, to Phleum pratense (e.g., Timothy grass);
• Positive specific IgE, defined as greater than or equal to IgE class 2 (0.7 kU/L), against Phleum pratense;
• A positive response to nasal allergen challenge with Phleum pretense, defined as an increase in TNSS greater than or equal to 7 points above baseline;
• For women of childbearing age, a willingness to use an effective form of contraception for the duration of the trial; and
• The ability to give informed consent and comply with study procedures.

Exclusion Criteria

• Prebronchodilator forced expiratory volume at 1 second (FEV1) less than 70% of predicted value at either screening or baseline visit;
• A clinical history of moderate to severe allergic rhinitis, according to the ARIA classification, due to tree pollen near or overlapping the grass pollen season;
• A clinical history of persistent asthma and/or requiring regular inhaled corticosteroids for > 4 weeks per year outside of the grass pollen season;
• A clinical history of moderate- severe allergic rhinitis, according to the ARIA classification, caused by an allergen to which the participant is regularly exposed;
• 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, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment;
• History of chronic sinusitis, defined as a sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, and ear pain, pressure, or fullness.
• At randomization, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
• Any tobacco smoking within the last 6 months or a history of ≥ 10 pack years;
• Previous treatment by immunotherapy with grass pollen allergen within the previous 5 years.
• Any history of grade 4 anaphylaxis due to any cause as defined by the World Allergy Organization (WAO) grading criteria for immunotherapy;
• History of bleeding disorders or treatment with anticoagulation therapy;
• History of anti-IgE monoclonal antibody treatment;
• Ongoing systemic immunosuppressive treatment;
• History of intolerance to the study therapy, rescue medications, or their excipients;
• For women of childbearing age a positive serum or urine pregnancy test with sensitivity of less than 50 mIU/mL within 72 hours before the start of study therapy;
• The use of any investigational drug within 30 days of the screening visit; or
• The presence of any medical condition that the investigator deems incompatible with participation in the trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Durham, MD

Role: STUDY_CHAIR

Imperial College London

Locations

Royal Brompton Hospital

London, , United Kingdom

Countries

United Kingdom

References

Cox LS. Sublingual Immunotherapy for Allergic Rhinitis: Is 2-Year Treatment Sufficient for Long-term Benefit? JAMA. 2017 Feb 14;317(6):591-593. doi: 10.1001/jama.2017.0128. No abstract available.

Reference Type: BACKGROUND

PMID: 28196239 (View on PubMed)

Scadding GW, Calderon MA, Shamji MH, Eifan AO, Penagos M, Dumitru F, Sever ML, Bahnson HT, Lawson K, Harris KM, Plough AG, Panza JL, Qin T, Lim N, Tchao NK, Togias A, Durham SR; Immune Tolerance Network GRASS Study Team. Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial. JAMA. 2017 Feb 14;317(6):615-625. doi: 10.1001/jama.2016.21040.

Reference Type: RESULT

PMID: 28196255 (View on PubMed)

Altman MC, Segnitz RM, Larson D, Jayavelu ND, Smith MT, Patel S, Scadding GW, Qin T, Sanda S, Steveling E, Eifan AO, Penagos M, Jacobson MR, Parkin RV, Shamji MH, Togias A, Durham SR. Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy. J Allergy Clin Immunol. 2023 Nov;152(5):1247-1260. doi: 10.1016/j.jaci.2023.06.025. Epub 2023 Jul 15.

Reference Type: DERIVED

PMID: 37460024 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.Creating an account for ITN TrialShare is free and allows for searching studies of interest.

View Document

Document Type: Synopsis, Adverse Events, -Data and Reports, -Schedule of Assessments

TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.Creating an account for ITN TrialShare is free and allows for searching studies of interest.

View Document

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Disease (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

http://www.immunetolerance.org/

Immune Tolerance Network (ITN)

http://www.itntrialshare.org

Immune Tolerance Network (ITN) TrialShare: open public access to participant-level data available for this trial

http://www.ucsf.edu/

University of California, San Francisco (UCSF)

http://www3.imperial.ac.uk/

Imperial College London

Other Identifiers

2010-023536-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DAIT ITN043AD

Identifier Type: -

Identifier Source: org_study_id