Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy

NCT01449786 | Completed Phase 2 DMC

• 1 other identifier: TK01/2011
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

More than 70% of birch pollen allergic patients suffer from allergic reactions to certain foods, e.g. stone fruits, hazelnut and some vegetables. However, specific immunotherapy (SIT) with birch pollen extract is not effective for the treatment of associated food allergy in a substantial number of patients. Based on our previous clinical and immunological investigations of birch pollen related food allergy (BPRFA) the investigators hypothesize that for effective SIT of this abundant food allergy the disease-eliciting food allergens should be employed. To prove this concept, the investigators aim to sublingually administer the major apple allergen, Mal d 1, to birch pollen-allergic patients with concomitant apple allergy and evaluate clinical and immunological effects of this treatment. The investigators choose Mal d 1 as model food allergen because (i) its cross-reactivity with Bet v 1 has been well characterized,(ii) apple is the most frequent trigger for BPRFA and (iii) recombinant(r)Mal d 1 was well tolerated after sublingual administration to 20 birch pollen-allergic patients in a previous study. Sublingual administration of a defined concentration of GMP-rMal d 1 will be compared with equal doses of GMP-rBet v 1 as a positive control and placebo-treatment. Clinical parameters will include skin prick tests (SPT) and objective and subjective assessment of apple and birch pollen-induced allergic symptoms. Immunological parameters will comprise the analysis of antibody and T cell responses to Mal d 1 and Bet v 1 as well as the evaluation of basophil activation. The proposed pilot study will be a first investigation of the concept to specifically treat BPRFA with the involved food allergens and thus, represents an important step in the development of an efficient and safe therapy in the future.

Conditions

Birch Pollen Related Apple Allergy; Birch Pollen Allergy

Keywords

Mal d 1, Bet v 1, sublingual immunotherapy,

Outcome Measures

Primary Outcomes (1)

• allergen concentration to induce allergic reactions in the oral cavity as a measure of efficacy (oral provocation test)

  To measure the clinical effects on apple-induced OAS, open food challenges (OFC) with every 30 minutes increasing doses of GMP-rMal d 1 will be performed before and after the treatment period.

  1 year

Secondary Outcomes (2)

• T cell proliferation and cytokine production as a measure of tolerance induction

  1 year

• allergen specific antibody response

  1

Study Arms (3)

treatment with rMal d 1

EXPERIMENTAL

these apple and birch pollen allergic patients are treated with daily sublingual application of 25µg recombinant Major apple allergen, Mal d 1 during 4 months

Drug: rMal d 1

treatment with rBet v 1

ACTIVE COMPARATOR

These apple and birch pollen allergic patients are treated with daily sublingual application of 25µg recombinant Major birch pollen allergen,Bet v 1 during 4 months

Drug: rBet v 1

treatment with placebo drops

PLACEBO COMPARATOR

These apple and birch pollen allergic patients are treated daily with placebo applied sublingually during 4 months

Other: placebo drops

Interventions

rMal d 1 DRUG

25 µg daily as sublingually administered drops, 16 weeks

treatment with rMal d 1

rBet v 1 DRUG

25 µg daily administered sublingually as drops over 16 weeks

treatment with rBet v 1

placebo drops OTHER

25 µg of placebo Drops daily administered sublingually over 16 weeks

treatment with placebo drops

Eligibility Criteria

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

You may qualify if:

• otherwise healthy persons between 18 und 50 years of age;
• positive history of rhinoconjunctivitis to birch pollen
• oral allergy syndrome(OAS) to apple
• positive skin prick test (SPT) reaction to birch pollen and apple
• specific IgE for Bet v 1 and Mal d 1

You may not qualify if:

• Persons who due to their physical or mental state are not able to provide informed consent.
• Persons with underlying illnesses such as severe cardiopulmonary, malignant and/or autoimmune diseases
• Persons suffering from Hyper-IgE syndrome
• Persons receiving SIT during the past 5 years
• persons suffering from severe allergic reactions to apple such as generalized urticaria, asthma and/or anaphylaxis
• persons suffering from severe bronchial asthma to birch pollen
• persons suffering from pathological alterations of the lips and oral mucosa
• persons who are prescribed a treatment with immune-suppressive drugs, anti-histamines, leukotriene-antagonists or psychotropic drugs with anti-histaminic effects
• persons using ß-blockers
• Pregnant woman

Sponsors & Collaborators

• Medical University of Vienna: lead
• Austrian Science Fund (FWF): collaborator

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

Location

Study Officials

• Barbara Bohle, PhD, Prof.

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

• Tamar Kinaciyan, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Ass.Prof.

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: October 10, 2011
• Study Start: March 14, 2012
• Primary Completion: February 28, 2014
• Study Completion: December 20, 2016
• Last Updated: April 13, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)