Long-Term Effects of Sublingual Grass Therapy

NCT01335139 | Completed Phase 2 DMC

• 2 other identifiers: DAIT ITN043AD2010-023536-16
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

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.

Conditions

Rhinitis, Allergic, Seasonal

Keywords

sublingual immunotherapy; subcutaneous immunotherapy

Outcome Measures

Primary Outcomes (1)

• Nasal Response to Allergen Challenge

  Defined as the average of the Total Nasal Symptom Score (TNSS) area under the curve (AUC) measured at 0 to 1 hours and the AUC measured at 1 to 10 hours after allergen challenge. The primary outcome consists of the comparison of SLIT + SCIT placebo versus SLIT placebo + SCIT placebo.

  3 years

Secondary Outcomes (15)

• Skin Late Phase Response (LPR) to Intradermal Testing

  Baseline (Time 0) and 1,-2, and -3 years

• Skin Early Phase Response (EPR) to Intradermal Testing

  Baseline (Time 0) and 1, -2, and -3 years

• Nasal LPR

  Baseline (Time 0) and 1, -2, and -3 years

• Nasal EPR

  Baseline (Time 0) and 1, -2, and -3 years

• Peak Total Nasal Symptom Score (TNSS) EPR

  Baseline (Time 0) and 1, -2, and -3 years

Study Arms (3)

SCIT + Placebo

EXPERIMENTAL

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

Biological: Subcutaneous immunotherapy (SCIT); Other: Placebo

SLIT + Placebo

EXPERIMENTAL

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

Biological: Sublingual immunotherapy (SLIT); Other: Placebo

Placebo + Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Sublingual immunotherapy (SLIT) BIOLOGICAL

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

Also known as: Grazax®

SLIT + Placebo

Subcutaneous immunotherapy (SCIT) BIOLOGICAL

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

Also known as: Alutard SQ Grass Pollen®

SCIT + Placebo

Placebo OTHER

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

Placebo + Placebo; SCIT + Placebo; SLIT + Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator
• Imperial College London: collaborator

Study Sites (1)

Royal Brompton Hospital

London, SW3 6LY, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 28196239 BACKGROUND

• 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.

  PMID: 28196255 RESULT

• 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.

  PMID: 37460024 DERIVED

Related Links

• National Institute of Allergy and Infectious Disease (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Immune Tolerance Network (ITN)
• Immune Tolerance Network (ITN) TrialShare: open public access to participant-level data available for this trial
• University of California, San Francisco (UCSF)
• Imperial College London

MeSH Terms

Conditions

Rhinitis, Allergic, Seasonal

Interventions

Sublingual Immunotherapy; Grazax

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Stephen Durham, MD

  Imperial College London

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2011
• First Posted: April 14, 2011
• Study Start: March 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: June 2, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)