Clinical Trial Results:
A double blind placebo controlled randomised trial to study the effects of birch pollen specific immunotherapy (BP-SIT) on the symptoms of the oral allergy syndrome in adult patients.
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Summary
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EudraCT number |
2011-004078-26 |
Trial protocol |
GB |
Global end of trial date |
03 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Jan 2020
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First version publication date |
05 Jan 2020
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Other versions |
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Summary report(s) |
OAS Findings Summary |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
10/143/FRE
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Additional study identifiers
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ISRCTN number |
ISRCTN01027357 | ||
US NCT number |
NCT01431859 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Brighton and Sussex University Hospitals Trust
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Sponsor organisation address |
Royal Sussex County Hospital Eastern Road, Brighton, United Kingdom, BN2 5BE
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Public contact |
Mr Scott Harfield, Brighton and Sussex University Hospitals Trust, 044 01273 696955, Scott.Harfield@bsuh.nhs.uk
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Scientific contact |
Mr Scott Harfield, Brighton and Sussex University Hospitals Trust, 044 01273 696955, Scott.Harfield@bsuh.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Jul 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Mar 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Mar 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Does immunotherapy (the process of giving small but increasing doses of birch pollen as injections under the skin) improve symptoms of mouth and throat itch, irritation and swelling on eating apples in patients with oral allergy syndrome?
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Protection of trial subjects |
Patients were given full advice and information through the participation information sheet before being asked if they wished to participate in the study and once involved they were asked at each visit whether they wished to continue and were free to withdraw from the study. After treatment the patients were monitored to ensure they were in no distress and all was well before being told that they were free to return home. They were given the contact numbers of the research staff in case they had any queries and also the contact details of the Patient Advice and Liaison Service
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Background therapy |
None | ||
Evidence for comparator |
This was a placebo controlled trial. A placebo solution was supplied as a comparator. The placebo preparation used is the verum solution without any added allergen substance, also termed Allergovit diluent. | ||
Actual start date of recruitment |
06 Aug 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 32
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Worldwide total number of subjects |
32
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EEA total number of subjects |
32
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
32
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 32 patients were randomised and contributed data. They were recruited at two sites in the UK:Royal Sussex County Hospital, Brighton and Homerton Hospital London between 2012 and 2017 | |||||||||||||||
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Pre-assignment
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Screening details |
143 patients were screened in Brighton and 16 at Homerton. The lower number at Homerton being due to them having a database which allowed them to pre-identify potential patients. | |||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||
Blinding implementation details |
The active food challenges provided to the patients consisted of a base containing yogurt, orange juice, apple juice, processed apple sauce and oatflakes, to which aliquots of freshly shredded apple are added. Each meal was prepared by an investigator 5 minutes before administration and handed to the supervising clinician who remains unaware of the content. Placebo meals are identical but contain no fresh apple. The vaccines and placebo were prepared by the same manufacturer
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Treatment | |||||||||||||||
Arm description |
The treatment arm recieved a modified birch allergen vaccine (Allergovit) in which the allergenic proteins have been treated with aldehydes to reduce their potential for side-effects, while retaining their ability to be recognised by T-cells (the principal immunological target for SIT). This type of vaccine is in widespread use in Europe. | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Allergovit
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
This consisted of a 7 week course of subctaneous injections.
Strength = 1,000 TU/ml ,Dosage in ml 0.1, 0.2, 0.4, 0.8. Strength = 10, 000 TU/ml Dosage in ml 0.15, 0.3, 0.6
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Arm title
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Placebo | |||||||||||||||
Arm description |
The placebo preparation used was the verum solution without any added allergen substance, also termed Allergovit diluent. | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Allergovit
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
This consisted of a 7 week course of subctaneous injections.
Strength = 1,000 TU/ml ,Dosage in ml 0.1, 0.2, 0.4, 0.8. Strength = 10, 000 TU/ml Dosage in ml 0.15, 0.3, 0.6
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treatment
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Reporting group description |
The treatment arm recieved a modified birch allergen vaccine (Allergovit) in which the allergenic proteins have been treated with aldehydes to reduce their potential for side-effects, while retaining their ability to be recognised by T-cells (the principal immunological target for SIT). This type of vaccine is in widespread use in Europe. | ||
Reporting group title |
Placebo
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Reporting group description |
The placebo preparation used was the verum solution without any added allergen substance, also termed Allergovit diluent. | ||
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End point title |
Double Blind Placebo Controlled Food Challenge [1] | |||||||||
End point description |
The change in level was calculated for year 1 and year 2 as Year 1 or 2 - Year 0. A negative change indicates a higher threshold at Year 0 and therefore a worse outcome at year1/2. A positive change indicates a higher threshold at Year 1 or 2 and therefore a positive outcome.
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End point type |
Primary
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End point timeframe |
Year 1 and year 2
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: See attached documents for results |
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Attachments |
Untitled (Filename: OAS analysis 1.0 signed.pdf) |
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End point title |
Skin test sensitivity | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Two years
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Adverse events information [1]
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Timeframe for reporting adverse events |
For the duration of the study
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
18
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| Frequency threshold for reporting non-serious adverse events: 1% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: See attached document for list of AEs there were no SAEs |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Nov 2011 |
1. The protocol has been amended to more accurately reflect the contra-indications contained within the SmPC.
2. Further information about the manufacture and control of placebo is included
3. A copy of the manufacturer’s authorisation for the placebo is included.
4. The “Allergovit diluent” is now specified as being the same as the placebo product in the protocol.
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08 Oct 2012 |
1. GP Practices to search their databases for hay fever sufferers and invite them to take part in the study by sending them the GP Invitation Letter (Version 1.2, dated 13/08/2012).
2. The protocol was amended so that people with autoimmune diseases who are not on immunosuppressive drugs (e.g. Coeliac disease) could be included.
3. Diary card approved.
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09 Oct 2012 |
The addition of PIC sites. |
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24 Jan 2013 |
Addition of an open apple challenge at the end of the double blind placebo controlled food challenges. |
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06 Jun 2013 |
Homerton Hospital becoming an additional site for the study. |
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10 Jun 2013 |
Amendment to the protocol, patient information sheet and advert to be more generic, and less BSUH specific in order for the study to become multi-centred. Also the addition of an invitation letter to those patients who are interested in research. |
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23 Sep 2013 |
The protocol was updated to allow appropriately qualified and trained nurses to give the IMP injection, as well as a doctor. |
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28 Oct 2013 |
To amend the recruitment procedure so that delegated nurses can consent patients (but eligibility will still be confirmed by a doctor). No documentation is affected in this amendment. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
