Study to assess the clinical efficacy and safety of SUBLIVAC FIX Birch immunotherapy in patients with allergic rhinitis/rhinoconjunctivitis caused by birch pollen

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2013-005550-30-SK
• Date of registration: 07/04/2014
• Prospective Registration: Yes
• Primary sponsor: HAL Allergy B.V.
• Public title: Study to assess the clinical efficacy and safety of SUBLIVAC FIX Birch immunotherapy in patients with allergic rhinitis/rhinoconjunctivitis caused by birch pollen
• Scientific title: A randomized, double-blind, placebo-controlled (DBPC), parallel group study to assess the clinical efficacy and safety of SUBLIVAC FIX Birch immunotherapy in patients suffering from allergic rhinitis/rhinoconjunctivitis caused by birch pollen. SB/0042 study - SUBLIVAC FIX Birch Phase III short-term efficacy
• Date of first enrolment: 28/04/2014
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005550-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Czech Republic, Germany, Poland, Slovakia

Contacts

• Name: Clinical Trial Management
• Affiliation: HAL Allergy B.V.

• Name: Clinical Trial Management
• Affiliation: HAL Allergy B.V.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent
2. Age = 18 and =65 years
3. Moderate-to-severe birch pollen induced allergic rhinitis/rhinoconjunctivitis based on ARIA classification for at least 2 consecutive years24
4. FEV1 > 70% (of predicted value) for patients with a history of asthma, FEV1 > 70% or PEF > 80% (of predicted value) for patients without a history of asthma
5. Positive SPT for birch pollen (mean wheal diameter = 3mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter = 3mm)) assessed during screening.
6. Serum specific anti-birch IgE concentration >0.7 U/ml
Inclusion criteria to be assessed at Visit 2 before randomisation:
7. Patients should be willing and capable to complete an e-diary daily during the birch pollen season (= 60% compliance in completion between Visit 1 and 2).
8. A positive Nasal Provocation Test to birch pollen (per appendix 3) at Visit 2 (Lebel score = 6) or a documented positive test within 1 year before start of treatment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 360
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
1. Patients sensitized and symptomatic to pets should not be included if they are regularly exposed to pets
2. Specific immunotherapy (SCIT or SLIT) with birch pollen or a cross-reacting allergen within the last 5 years
3. SPT positive (mean wheal diameter = 3mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter = 3mm)) patients to allergen(s) other than birch pollen, in the absence of a negative provocation test for this allergen(s) (within 1 year), who are expected to have clinically relevant symptoms during the birch pollen season
4. Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the last 5 years
5. (Ongoing) allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) during the study period
6. Vaccination one week before start of treatment and/or during the up-dosing phase
7. Treatment with experimental products within the last 3 months or biologicals (including anti-IgE or TNF- a treatment) within the last 6 months or during the study
8. Uncontrolled asthma or other active respiratory diseases
9. Clinically significant chronic sinusitis, ocular infection or severe inflammation of the oral mucosa
10. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
11. Active malignancies or any malignant disease in the last 5 years
12. Acute or chronic disease that in the opinion of the investigator is an additional risk for the patients, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, or haematological disorders
13. Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma)
14. Use of systemic corticosteroids 4 weeks before the study
15. Treatment with systemic or local ß-blockers
16. Known hypersensitivity to any of the excipients (Disodium phosphate dihydrate, Sodium dihydrogen phosphate dehydrate, aminocaproic acid, Peppermint oil, Caramel Colorant or Glycerol)
17. A positive urine pregnancy test, lactation or inadequate contraceptive methods (adequate methods: oral contraceptives, IUD, condom use and having no sexual relationship with a man)
18. Alcohol-, drug or medication abuse
19. Lack of co-operation or compliance
20. Severe psychiatric, psychological, or neurological disorder
21. Any physical or mental condition that precludes administration or allergen-specific immunotherapy, compliance or participation in a clinical trial
22. Patients who are employees of the department, 1st grade relatives, or partners of the investigator
23. Patients who have planned holidays outside the country for more than 7 continuous days during the defined pollen season (1st of March till 31st of May)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Ear, nose and throat diseases [C09]

Moderate to severe birch pollen induced allergic rhinitis/rhinoconjunctivitis with or without mild to moderate persistent asthma.
MedDRA version: 17.0 Level: LLT Classification code 10001726 Term: Allergic rhinitis due to pollen System Organ Class: 100000004870

Intervention(s)

Product Name: SUBLIVAC FIX Birch 40.000 AUN/ml
Product Code: SUBLIVAC FIX Birch
Pharmaceutical Form: Oromucosal drops
INN or Proposed INN: Allergen extract of Betula verrucosa
Current Sponsor code: SUBLIVAC FIX BIRCH
Concentration unit: Other
Concentration type: equal
Concentration number: 40.000-
Pharmaceutical form of the placebo: Oromucosal drops
Route of administration of the placebo: Sublingual use

Primary Outcome(s)

Secondary Objective: Secondary objectives:
• To assess clinical efficacy of sublingual immunotherapy with SUBLIVAC FIX Birch during the peak pollen season compared to placebo
• To assess the effect of sublingual immunotherapy with SUBLIVAC FIX Birch on Quality of Life (QoL) during the pollen season compared to placebo
• Changes in serum specific immunoglobulin levels after treatment with sublingual immunotherapy with SUBLIVAC FIX Birch compared to placebo
•To assess the effect of sublingual immunotherapy with SUBLIVAC FIX Birch on the percentage of responders compared to placebo

Safety objectives:
• Safety and tolerability of sublingual immunotherapy with SUBLIVAC FIX Birch compared to placebo

Timepoint(s) of evaluation of this end point: During Birch pollen season (e-diary)

Main Objective: Primary Objective:
To assess clinical efficacy of sublingual immunotherapy with SUBLIVAC FIX Birch (40.000 AUN/ml), compared to placebo, in patients suffering from birch pollen induced rhinitis/rhinoconjunctivitis, measured by a combined rhinoconjunctivitis symptoms score and medication score during the birch pollen season.

Primary end point(s): The primary endpoint is the difference in mean Combined Symptom Medication Score (CSMS) between the active vs. placebo treatment group, assessed during birch pollen season.

Secondary Outcome(s)

Secondary end point(s): The secondary endpoints of the study are:
1. Difference in mean CSMS between the active vs. placebo treatment group, assessed during the birch peak pollen season
2. Difference in daily Symptom Score (dSS) assessed during the birch (peak) pollen season between the active vs. placebo treatment group.
3. Difference in daily Medication Score (dMS) assessed during the birch (peak) pollen season in the active vs. placebo treatment group.
4. Difference between active and placebo treatment in Quality of Life (QoL) during the birch pollen season and End Of Treatment (EOT), determined by standardized (rhinoconjunctivitis) QoL questionnaire (RQLQ-S and EQ-5D) for all patients and for patients with birch pollen induced concomitant asthma by an additional asthma control questionnaire (ACQ)
5. Differences in serum specific immunoglobulin levels (IgE, IgG, IgG4) in the active vs. placebo treatment group after treatment.
6. Differences in number of ‘well days’ and ‘severe days’ between the active and placebo treatment
The exploratory endpoint of the study is:
7. Difference in mean CSMS between the active and placebo treatment group using the placebo score-based period.
Safety endpoints:
8. Safety assessed by local and systemic reactions, (serious) adverse events, blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG in the active treatment vs. placebo group before, during and after treatment.

Timepoint(s) of evaluation of this end point: Endpoints no 1, 2, 3:
birch peak pollen season
Endpoint 4:
during the birch pollen season and at the End Of Treatment (EOT),
Endpoint 5:
after treatment
Endpoint 6:
during the birch pollen season
Endpoint 7:
placebo score-based period (four weeks with the highest CSMS reported in the placebo group determined per site)
Endpoint 8:
before ( Visit 1), during (Visits 5 ) and after treatment (Visit 8)

Secondary ID(s)

SB/0042

2013-005550-30-CZ

Source(s) of Monetary Support

HAL Allergy B.V.