Clinical trial NCT00973453: Study With High Dose PURETHAL Mites in Allergic Rhinitis/Rhinoconjunctivitis Patients
Official title: Dose Tolerability Study With High Dose PURETHAL Mites in Allergic Rhinitis / Rhinoconjunctivitis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Rhinitis
Allergic Rhinoconjunctivitis
Keywords: non-seasonal allergy
house dust mite
immunotherapy
dose tolerability
Lead sponsor: HAL Allergy
Sponsor class: INDUSTRY
First posted: 2009-09-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: The aim of the study is to establish the maximum tolerated dose of PURETHAL Mites that is achieved by 90% of the patients with less than 20% of the injections giving rise to a swelling of \> 5 cm and the optimal regimen to reach this maximum dose will be determined.

Detailed description: The tolerability and safety of three different initial treatment regimens PURETHAL mites in patients with allergic rhinitis / rhinoconjunctivitis induced by house dust mites will be evaluated and the optimal regimen to reach the maximum tolerated dose will be determined. The maximum intended dose is a 4-fold dosage compared to the currently used maintenance dose of PURETHAL Mites. The tolerability and safety of the injections will be examined by means of determining the early and late local and systemic reactions. In addition, short-term efficacy of this high dose PURETHAL mites will be determined by means of the Clinical index score (CIS) and two surrogate efficacy markers; the conjunctival provocation test (CPT) and serum levels of allergen specific immunoglobulins (IgG and IgE). These efficacy parameters are purely indicative and not decisive for the further clinical development of PURETHAL Mites.

Eligibility criteria: Inclusion Criteria:

1. Patients with perennial rhinitis or rhinoconjunctivitis, with or without mild asthma (FEV1 \> 70%) for at least 2 years. with allergic symptoms related to HDM
2. Positive CPT test to HDM Der p, dose ≤10,000 AUeq/ml
3. Positive SPT to HDM Der p or Der f (mean wheal diameter ≥ 3mm)
4. Specific serum IgE-test (ssIgE \> 0.7 U/ml) for HDM
5. Age ≥ 18 years
6. Written informed consent given

Exclusion Criteria:

1. Patients with concomitant sensitization i.e. positive SPT (mean wheal diameter ≥ 3 mm) to other allergens than HDM should not be included if they have clinical symptoms at the time of inclusion, related to the other allergen
2. Patients sensitized to pets should not be included if they live together with these pets or have clinical symptoms
3. Immunotherapy (including sublingual) with HDM within the last 5 years
4. Immunotherapy (including sublingual) during the study period
5. Chronic asthma or emphysema, particularly with a FEV1 ≤ 70% of predicted value or use of inhalation corticosteroids
6. Serious immuno-pathologic diseases or malignancies (including auto-immune diseases, tuberculosis)
7. Symptomatic coronary heart diseases or severe (even under treatment) arterial hypertension
8. Diseases with a contra-indication for the use of adrenaline
9. Patients who are using other aluminium preparations, e.g. antacids
10. Severe kidney disease
11. Use of systemic steroids
12. Treatment with systemic and local Beta-blockers or immunosuppressive drugs
13. Active infection of the target organs (nose or eyes)
14. Severe atopic dermatitis in case systemic immunosuppressive medication is used
15. Participation in a clinical study with a new investigational drug within the last 3 months
16. Pregnancy, lactation or inadequate contraceptive measures (adequate contraceptive measures will be the use of a contraceptive device or -pill)
17. Alcohol- or drug abuse
18. Lack of co-operation or severe psychological disorders
19. Institutionalisation by official or judicial order

Primary outcomes:
measure: Early Local Reactions (ELR) occurring 15 minutes after injection. Less than 20% of the injections should give rise to swelling at the injection site of > 5 cm in diameter occurring 15 minutes after injection.
timeFrame: 17, 14 or 11 weeks per patient for the respective groups
Secondary outcomes:
measure: Late Local Reactions (LLR) occurring within 24 hours after injection, and systemic reactions (SR). General adverse events will be recorded during complete study period.
timeFrame: 17, 14 or 11 weeks per patient for the respective groups
measure: Clinical index score (CIS) during the study compared to baseline score (before treatment).
timeFrame: weekly during per patient treatment periods of 17, 14 or 11 weeks for the respective groups
measure: Conjunctival provocation test one week after reaching 10,000 AUeq, 20,000 AUeq, or 40,000 AUeq for the respective groups compared to baseline.
timeFrame: after 7 weeks of treatment
measure: Conjunctival provocation test 2 weeks after the patients have received two maintenance dosages compared to baseline score.
timeFrame: 17, 14 or 11 weeks for the respective treatment groups
measure: Specific IgE and IgG measured 2 weeks after the patients have received two maintenance dosages compared to baseline score.
timeFrame: 17, 14 or 11 weeks for the respective treatment groups
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Allergie-Centrum Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité Campus Mitte, Universitätsmedizin Berlin
city: Berlin
country: Germany
facility: Hals, Nasen- und Ohrenheilkunde
city: Berlin
country: Germany
facility: Allergy & Asthma Center Westend
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Schorndorf
country: Germany
facility: Allergologie HNO-Heilkunde
city: Stuttgart
country: Germany
facility: Klinik für Dermatologie und Allergie, Krankenhaus Bad Cannstatt
Study officials:
affiliation: UZDAA, Untersuchungszentrum Dermatologie, Allergologie und Asthma, Berlin, Germany
name: Jörg Kleine-Tebbe, MD
role: STUDY_CHAIR
References: