SUBLIVAC FIX Mite Mixture Dose Tolerability Study

House Dust Mite Allergy Clinical Trial

— DTS  

Official title:

A Randomized, Double-blind, Placebo-controlled Study to Determine Tolerability and Safety of Different Dosages of SUBLIVAC FIX Mite Mixture in Patients With Allergic Rhinitis / Rhinoconjunctivitis Caused by House Dust Mites

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02345278
• Other study ID #: SM/0044
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 19, 2015
• Last updated: December 1, 2015
• Start date: May 2015
• Est. completion date: November 2015

Study information

• Verified date: December 2015
• Source: HAL Allergy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

Allergic rhinitis/rhinoconjunctivitis is a symptomatic disorder of the nose induced by an immunoglobulin E (IgE) mediated inflammatory response. Treatment may involve pharmacotherapy and specific immunotherapy (IT). IT represents the only treatment that might alter the natural course of the disease. The amount of administered allergen is crucial for both efficacy and safety of specific IT. SUBLIVAC FIX Mite mixture is a preparation for sublingual IT (SLIT) and is indicated for the treatment of allergic disorders such as allergic rhinitis and rhinoconjunctivitis, caused by sensitisation to house dust mite (HDM) allergens.

According to the European Medicines Agency Guideline on the clinical development of products for specific IT for the treatment of allergic diseases, products should be tested at different dosages to provide preliminary data on safety and tolerability with regard to the maximum tolerated dose and suitable dose escalation scheme. This trial is designed to investigate the tolerability and safety of different dosages of SUBLIVAC FIX Mite mixture.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent

2. Male or female patients, age = 18 = 60 years

3. Patients with allergic rhinitis or rhinoconjunctivitis induced by HDM for at least 1 year, with or without concomitant at least partly controlled asthma

4. Patients with a history of concomitant asthma should have a FEV1 > 70% (of predicted value) at inclusion. Patients without a history of asthma should have a FEV1 > 70% or a PEF > 80% (of predicted value)

5. Positive SPT to HDM D. pter or D. far (mean wheal diameter = 3 mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter = 3 mm) at screening

6. Allergen specific serum IgE (ssIgE) level in serum for HDM D. pter or D. far (> 0.7 U/ml), assessed at screening

Exclusion Criteria:

1. Patients with concomitant sensitization i.e. positive SPT (mean wheal diameter = 3 mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter = 3 mm) who are expected to have clinically relevant symptoms during the treatment period

2. Patients sensitized and symptomatic to pets who are regularly exposed to pets

3. Completed allergen-specific immunotherapy (SCIT or SLIT) with HDM within the last 5 years

4. Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the last 5 years

5. Allergen-specific immunotherapy (SCIT or SLIT) with other allergens than HDM during the study period

6. Any other vaccination one week before start of treatment and during the up-dosing phase

7. Any anti-IgE therapy within the last 6 months prior to inclusion and during study

8. Active inflammatory disease in the mouth (e.g periodontitis, oral mucosal lichen planus)

9. Known hypersensitivity to any of the excipients (i.e. Disodium phosphate dihydrate, Sodium dihydrogen phosphate dihydrate, Aminocaproic acid, Glycerol, Peppermint oil, Caramel Colorant) of SLIT solution

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. A chronic or acute disease that in the opinion of the investigator might place the patient at an additional risk, 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 start treatment

15. Treatment with systemic or local beta-blockers

16. Clinically significant chronic sinusitis or ocular infection

17. Participation in a clinical study with a new investigational drug within the last 3 months or a biological within the last 6 months prior to the study or during the study

18. Pregnancy, lactation or inadequate contraceptive measures (acceptable forms of birth control include Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections) or condom combined with a diaphragm including spermicidal cream). Also acceptable for women is surgical sterilization (removal of the uterus or ovaries or tubal ligation ("tied tubes")), if they are postmenopausal (12 consecutive months without a period) for at least 2 years, or having no sexual relationship with a man.

19. Alcohol, drug, or medication abuse within the past year and during the study

20. Any lack of co-operation or compliance

21. Severe psychiatric, psychological, or neurological disorders

22. Patients who are employees of the department or study site; 1st grade relatives, partners of the investigator, or patients who are dependent on the sponsor

23. Any physical or mental condition that precludes administration of allergen-specific immunotherapy, compliance or participation in a trial

24. Patients who are placed in an institution due to governmental or judicial directive

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• House Dust Mite Allergy

Intervention

Drug:
• SUBLIVAC FIX Mite mixture
Study medication will be taken sublingually once a day. Patients will start with one drop and increase the dose by one drop each consecutive day until the maintenance dose (5 drops/day) is reached. Drops should be kept under the tongue for 2-3 minutes before swallowing. After reaching the maintenance dose patients will be treated up to 1 month.

Other:
• Placebo
Study medication will be taken sublingually once a day. Patients will start with one drop and increase the dose by one drop each consecutive day until the maintenance dose (5 drops/day) is reached. Drops should be kept under the tongue for 2-3 minutes before swallowing. After reaching the maintenance dose patients will be treated up to 1 month.

Locations

Country	Name	City	State
Germany	Charite Universitatsmedizin Berlin, Allergiezentrum	Berlin
Germany	Praxis Dr.med.Elke Hippke	Berlin
Germany	HNO-Heilkunde Praxis	Chemnitz
Germany	HNO und Allergologie Praxis	Dresden
Germany	HNO-Praxis Dr. Uta Thieme	Duisburg
Germany	Universitatsklinikum Dusseldorf, Department Dermatology	Dusseldorf
Germany	HNO Praxis Gottingen	Gottingen
Germany	HNO Gemeinschaftspraxis	Heidelberg
Germany	HNO Praxis am Neckar	Heidelberg
Germany	Dr.med. Ulrich Neumann Praxis	Wolmirstedt

Sponsors (1)

Lead Sponsor	Collaborator
HAL Allergy

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of SUBLIVAC FIX Mite mixture (assessed by number and severity of local and systemic reactions)	Safety and tolerability of different dosages of SUBLIVAC FIX Mite mixture compared to placebo assessed by number and severity of local and systemic reactions.	1 month treatment	Yes
Secondary	Adverse Events	Safety of different dosages of SUBLIVAC FIX Mite mixture compared to placebo assessed by number and severity of Adverse Events	1 month treatment	Yes
Secondary	Clinical and laboratory parameters (Safety of different dosages of SUBLIVAC FIX Mite mixture)	Safety of different dosages of SUBLIVAC FIX Mite mixture compared to placebo assessed by clinical and laboratory parameters	1 month treatment	Yes
Secondary	Changes in immunoglobulin levels ((IgE, IgG, IgG4)	Changes in serum specific immunoglobulin levels (IgE, IgG, IgG4) after 1 month of treatment with different dosages of SUBLIVAC FIX Mite mixture compared to placebo	1 month	Yes
Secondary	Proportion of patients reaching maintenance dose within 10 days	Proportions of patients in the different treatment groups reaching maintenance dose within 10 days	10 days	Yes