The objective of the present study is to characterize the dose-response relationship of PURETHAL® Mites (PM) with a nasal provocation test in order to identify the optimal dose in terms of highest clinical efficacy and safety.
ID
Source
Brief title
Condition
- Allergic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the absolute difference in mean symptom score in the
TNPT between one year of treatment and baseline, among the different PM dose
groups versus placebo.
Secondary outcome
TNPT after 6 months of treatment, Average Adjusted Symptom Score (AdSS), Peak
Nasal Inspiratory Flow (PNIF), Serum immunoglobulin levels.
Background summary
In order to comply with the EMA guidelines on the development of specific
immunotherapy (SIT) - products (EMA Guideline, 2008), the current study is
designed to identify the optimal, safe and effective dose in HDM-sensitive
allergic rhinitis/rhinoconjunctivitis with or without concomitant asthma.
Due to the need of at least 4 active study arms in a DRF study (EMA Guideline,
2008), the use of a classical endpoint (symptom & medication score) as primary
parameter is not feasible because of the necessity of large sample sizes. We
have selected the titrated nasal provocation test (TNPT) as the primary
parameter. The TNPT is a reproducible exacerbation model of allergic rhinitis
often applied to evaluate the efficacy of anti-allergy medications (Proud,
2010).
Furthermore, the response to nasal allergen challenges is correlated to
symptom-medication scores during the relevant season and is an accepted
endpoint in DRF studies (Bousquet 1988, EMA Guideline, 2008). Previous studies
have found a significant effect of allergen specific
immunotherapy on allergen provocations in combination with clinical improvement
(Branco Ferreira 2005, Haugaard, 1993).
The optimal dose obtained from the DRF will be implemented in a 1-year
randomized, placebocontrolled, pivotal study in patients with HDM-induced
allergic rhinitis/ rhinoconjunctivitis.
Study objective
The objective of the present study is to characterize the dose-response
relationship of PURETHAL® Mites (PM) with a nasal provocation test in order to
identify the optimal dose in terms of highest clinical efficacy and safety.
Study design
Multi-centre, randomized, double-blind, placebo-controlled, 5 arms
parallel-group, dose range finding study. Phase II.
Intervention
Patients are trested with one of the following strengths of PURETHAL® Mites:
3.333 , 10.000 , 25.000 or 50.000 AUeq/dose or Placebo by subcutaneous
injection. The treatment duration is approximately one year.
Study burden and risks
The burden for the patient is comparable with the burden of regular
immunotherapy (e.g. the weekly visits to the physician during up-dosing and the
monthly visits during maintenance)
During the study the following additional assessments are performed:
- During one year the patient will visit the clinic 18 times. The visits will
last 1 - 4 hours, depending on the assessment schedule.
- At screening and at the final visit, a physical examination and ECG is
performed.
- In total, there will be tree blood draws (venapuncture) of approximately 15
ml per draw to assess safety laboratory parameters and immunoglobulin levels.
Additionally, there will be urine samples collected at these time points for
assessment of safety laboratory parameters.
- For asthmatic patients a PEF will also be measured during the study
before each injection. The injection will be postponed if the value is below
80%.
- The patient will undergo three nasal provocation tests (TNPT) during the
study (baseline, 6 months, one year). The patient will be dosed with increasing
concentrations of allergens per nasal spray and symptom scores and nasal
obstruction will be measured during approximately one hour.
- At every visit, the nasal inhalation flow will be measured with a peak
inhalation flow device.
- During screening a skin prick test will be performed and a pulmonary
assessment will be done (FEV1 of PEF).
- The patient will use a diary to record allergy symptoms, adverse events and
medication use.
Adverse drug reactions that can occur are considered to be mild, like redness,
swelling, or itching at the site of the injection. Hardly ever, skin reactions
or generalized itching can occur. These adverse events mostly resolve quickly
and need no further treatment.
Intensified systemic reactions (shortness of breath, urticaria or angioedema)
might occur in very rare cases. During the last five years only 5 of these
serious reactions have been reported. Life-threatening adverse events have
never been reported with the subcutaneous immunotherapy that is used in this
study.
By testing higher doses of PURETHAL® Mites adverse reactions can be expected
and there may be risks involved in this therapy that have not been identified
in studies done so far. In a previous study a dose of 4-time the dose that is
on the market was tested and defined as safe.
J.H. Oortweg 15-17
Leiden 2333 CH
NL
J.H. Oortweg 15-17
Leiden 2333 CH
NL
Listed location countries
Age
Inclusion criteria
1. Signed informed consent;2. Patients (male or female) must be >= 18 and <= 60 years at screening;3. Patients with allergic rhinitis or rhinoconjunctivitis for at least 1 year; allergic symptoms related to HDM, with or without concomitant clinically stable controlled mild to moderate asthma (according to GINA classification) (Koshak, 2007) ;4. Patients with a history of concomitant asthma should have a FEV1 > 70% at inclusion. Patients without a history of asthma should have a FEV1 > 70% or a PEF > 80%.;5. Positive SPT to HDM D. pter and/or D. far (mean wheal diameter >= 3mm compared to negative control and negative control should be negative, assessed within 1 year before randomization) ;6. Serum specific IgE-test (ssIgE) level for HDM D. pter or D. far at screening (> 0.7 U/ml);7. Positive TNPT for HDM D. pter extract at screening (Lebel score >= 6 at or below 10,000 AU/ml)
Exclusion criteria
1. Current clinically relevant symptoms of seasonal rhinitis/rhinoconjunctivitis caused by other allergen(s) than HDM (with a demonstrated positive SPT for this allergen) at the time of inclusion (to avoid interference with TNPT at inclusion);2. Patients sensitized to animals should not be included if they are symptomatic upon exposure and regularly exposed to animals ;3. Completed allergen-specific immunotherapy (SCIT or SLIT) with HDM within the last 5 years;4. Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) in the past 5 years ;5. Allergen-specific immunotherapy (SCIT or SLIT) with other allergens than HDM during the study period;6. Any vaccination one week before start of therapy and during the up-dosing phase ;7. Any anti-IgE therapy within the last 6 months prior to inclusion and during study ;8. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs;9. Active malignancies or any malignant disease in the past 5 years;10. 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 hematological disorders ;11. Moderate to severe nasal obstructive diseases such as polyps, septal deviations etc.;12. Clinically significant chronic sinusitis or ocular infection;13. Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma);14. Use of systemic corticosteroids within 4 weeks of screening;15. Treatment with systemic or local beta-blockers;16. 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;17. Pregnancy, lactation or inadequate contraceptive measures (contraceptive measures considered as adequate include appropriate use of oral contraception, i.m. contraception or a contraceptive device);18. Alcohol, drug, or medication abuse within the past year and during study;19. Any abnormal laboratory parameter at screening that in the opinion of the investigator is considered clinically relevant;20. Lack of co-operation or compliance;21. Severe psychiatric, psychological, or neurological disorders;22. Patients who are employees of the department, 1st grade relatives, or partners of the investigator;23. Expected changes in HDM exposure during the study (avoidance measures, move, etc.)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000393-61-NL |
| CCMO | NL36879.056.11 |