Study With High Dose PURETHAL Mites in Allergic Rhinitis/Rhinoconjunctivitis Patients

Allergic Rhinitis Clinical Trial

Official title:

Dose Tolerability Study With High Dose PURETHAL Mites in Allergic Rhinitis / Rhinoconjunctivitis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00973453
• Other study ID #: PM/0028
• Status: Completed
• Phase: Phase 2
• First received: September 7, 2009
• Last updated: September 9, 2011
• Start date: August 2009
• Est. completion date: August 2010

Study information

• Verified date: September 2011
• Source: HAL Allergy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Allergic Rhinitis
• Allergic Rhinoconjunctivitis
• Conjunctivitis
• Conjunctivitis, Allergic
• Rhinitis

Intervention

Drug:
• PURETHAL Mites 20,000 AUeq/ml
Group 1: slow regimen (12+2 injections) Initial treatment: incremental weekly dose of 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1.0, 1.2*, 1.6* and 2.0* ml Additional maintenance: 2 two-weekly injections 2.0* ml *Injection volumes larger than 1 ml will be given as 2 separate injections of equal volume within an area of 1 cm.
• PURETHAL Mites 20,000 AUeq/ml
Group 2: intermediate regimen (9+2 injections) Initial treatment: incremental weekly dose of 0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2*, 1.6* and 2.0* ml. Additional maintenance: 2 two-weekly injections 2.0* ml *Injection volumes larger than 1 ml will be given as 2 separate injections of equal volume within an area of 1 cm.
• PURETHAL Mites 20,000 AUeq/ml
Group 3: fast initial treatment (6+2 injections) Initial treatment: incremental weekly dose of 0.2, 0.4, 0.8, 1.2*, 1.6* and 2.0*ml. Additional maintenance: 2 two-weekly injections 2.0* ml *Injection volumes larger than 1 ml will be given as 2 separate injections of equal volume within an area of 1 cm.

Locations

Country	Name	City	State
Germany	Allergie-Centrum Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité Campus Mitte, Universitätsmedizin Berlin	Berlin
Germany	Allergy & Asthma Center Westend	Berlin
Germany	Hals, Nasen- und Ohrenheilkunde	Berlin
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Allergologie HNO-Heilkunde	Schorndorf
Germany	Klinik für Dermatologie und Allergie, Krankenhaus Bad Cannstatt	Stuttgart

Sponsors (1)

Lead Sponsor	Collaborator
HAL Allergy

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		17, 14 or 11 weeks per patient for the respective groups	Yes
Secondary	Late Local Reactions (LLR) occurring within 24 hours after injection, and systemic reactions (SR). General adverse events will be recorded during complete study period.		17, 14 or 11 weeks per patient for the respective groups	Yes
Secondary	Clinical index score (CIS) during the study compared to baseline score (before treatment).		weekly during per patient treatment periods of 17, 14 or 11 weeks for the respective groups	No
Secondary	Conjunctival provocation test one week after reaching 10,000 AUeq, 20,000 AUeq, or 40,000 AUeq for the respective groups compared to baseline.		after 7 weeks of treatment	No
Secondary	Conjunctival provocation test 2 weeks after the patients have received two maintenance dosages compared to baseline score.		17, 14 or 11 weeks for the respective treatment groups	No
Secondary	Specific IgE and IgG measured 2 weeks after the patients have received two maintenance dosages compared to baseline score.		17, 14 or 11 weeks for the respective treatment groups	No