Birch Pollen Related Apple AllergyPhase 2NCT01449786
Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy
A Phase 2 study testing rMal d 1 and rBet v 1 in people with Birch Pollen Related Apple Allergy and Birch Pollen Allergy, run by Medical University of Vienna at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Birch Pollen Related Apple Allergy, Birch Pollen Allergy
- What is being tested?
- rMal d 1 and rBet v 1
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteAustria
- Study dates
- 14 Mar 2012to 20 Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Being tested
- rMal d 1, rBet v 1, placebo drops
- Keywords
- Mal d 1, Bet v 1, sublingual immunotherapy,
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rMal d 1Drug
25 µg daily as sublingually administered drops, 16 weeks
rBet v 1Drug
25 µg daily administered sublingually as drops over 16 weeks
placebo dropsOther
25 µg of placebo Drops daily administered sublingually over 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Other: placebo drops |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (2)
T cell proliferation and cytokine production as a measure of tolerance induction
PBMC isolated from heparinised blood before, during and after sublingual administration of the treatment will be stimulated with titrated concentrations of rMal d 1 and rBet v 1, respectively. Proliferative and cytokine responses will be determined.
Measured: 1 year
allergen specific antibody response
measurement of IgE, IgG and IgA antibodies specific for Bet v 1 and Mal d 1
Measured: 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2011 (estimated)
- Study start14 Mar 2012
- Primary completion28 Feb 2014
- Study completion20 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Birch Pollen Related Apple AllergyStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Austrian Science Fund (FWF)
- Responsible party
- Principal investigator, Tamar Kinaciyan, MD, Medical University of Vienna
- Investigators
- Barbara Bohle, PhD, Prof., Principal investigator, Medical University of ViennaTamar Kinaciyan, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01449786
- Sponsor's protocol ID
- TK01/2011
- Status last verified
- Apr 2017
- First submitted
- 5 Oct 2011
- Last updated
- 13 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy
- ClinicalTrials.gov ID
- NCT01449786
- Acronym / sponsor ID
- TK01/2011
- Keywords
- Mal d 1, Bet v 1, sublingual immunotherapy,
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- Austrian Science Fund (FWF)
- Study start
- 14 Mar 2012 (actual)
- Primary completion
- 28 Feb 2014 (actual)
- Study completion
- 20 Dec 2016 (actual)
- First posted
- 10 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| treatment with rMal d 1 | Experimental | Drug: rMal d 1these apple and birch pollen allergic patients are treated with daily sublingual application of 25µg recombinant Major apple allergen, Mal d 1 during 4 months |
| treatment with rBet v 1 | Active comparator | Drug: rBet v 1These 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 |
| treatment with placebo drops | Placebo comparator | Other: placebo dropsThese apple and birch pollen allergic patients are treated daily with placebo applied sublingually during 4 months |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rMal d 125 µg daily as sublingually administered drops, 16 weeks | Drug | treatment with rMal d 1 |
| rBet v 125 µg daily administered sublingually as drops over 16 weeks | Drug | treatment with rBet v 1 |
| placebo drops25 µg of placebo Drops daily administered sublingually over 16 weeks | Other | treatment with placebo drops |
Primary outcome
allergen concentration to induce allergic reactions in the oral cavity as a measure of efficacy (oral provocation test)
Time frame: 1 year
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.
2 secondary outcomes
T cell proliferation and cytokine production as a measure of tolerance induction
Time frame: 1 year
allergen specific antibody response
Time frame: 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2017.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara Bohle, PhD, Prof. principal investigator
Medical University of Vienna
Tamar Kinaciyan, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rMal d 1 and rBet v 1 in people with Birch Pollen Related Apple Allergy and Birch Pollen Allergy, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
allergen concentration to induce allergic reactions in the oral cavity as a measure of efficacy (oral provocation test) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2017.