| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| ICD classification code: J 45.0 and J 30.1 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Allergic asthma and allergic rhinitis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001705 |
| E.1.2 | Term | Allergic asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039087 |
| E.1.2 | Term | Rhinitis allergic NOS |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To investigate the dose response relationship regarding efficacy and safety of an allergoid preparation of Phleum pratense in adult patients with IgE mediated allergic rhinitis / rhinoconjunctivitis with or without bronchial asthma. |
|
| E.2.2 | Secondary objectives of the trial |
1) To investigate the efficacy and tolerability of a 6-grasses pollen allergen mixture in adult patients with IgE mediated allergic rhinitis
2)To compare the efficacy and safety of the regular up-dosing regimen of the allergoid preparation of Phleum pratense, the 6-grasses mixture and the shortened up-dosing regimen of Phleum pratense.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Has the patient given informed consent according to local requirements before any trial-related activities? (A trial-related activity is any procedure that would not have been performed during the routine management of the patient and any other trial-related activity performed with trial specific diagnostics or with trial medication)
2. Is the patient a legally competent male or female outpatient, aged 18 – 65 years?
3. Does the patient suffer from IgE-mediated seasonal allergic rhinoconjunctivitis with or without asthma (controlled, acc. to GINA 2006) caused by grass pollen documented by
a) skin prick test (SPT) wheal for Timothy grass pollen and 6-grasses mixture ≥ 3mm in diameter and
b) histamine (0.1% histamine) wheal ≥ 3mm in diameter and
c) a negative NaCl control reaction < 2mm in diameter and
d) IgE result (RAST) ≥ 0.70kU/L to Timothy grass pollen and
e) main discomfort in the months: May, June and July
4. Does the patient with bronchial asthma at entry have a confirmed diagnosis of asthma and does his asthma has been classified as “controlled” according to GINA guidelines (version 2006)?
5. Has the patient been treated with anti-allergic medications for at least 2 years prior to enrolment? (Patients with perennial and continuously treated asthma have to be excluded, see “exclusion criteria” below.)
6. For female patients: Does the patient use effective contraception and does she have a negative pregnancy test result? (Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectibles, combined or oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. No pharmacological interactions are known for hormonal contraceptives and specific immunotherapeutic preparations.)
7. Has the patient a positive response to at least one out of two tested ICT concentrations at visit S2? The result of the late phase reaction (LPR) must be ≥ 20mm in mean diameter to at least one out of the two tested concentrations and has the patient a swelling area of the lower dose of the test solution ≤ than the swelling area of the higher dose?
|
|
| E.4 | Principal exclusion criteria |
For female subjects:
1. a positive pregnancy test at screening.
2. use an unacceptable and unreliable contraceptive method during the trial, as judged by the investigator.
3. Known Pregnancy or lactation period.
4. seeking to become pregnant during study duration.
General criteria:
5. weighing less than 40kg.
6. Unable to understand and comply with the requirements of the trial, as judged by the investigator.
7. Concurrent participation in any other clinical trial or participation in any other clinical trial during the previous 30 days.
8. Involvement in the planning and conduct of the trial.
9. Allergopharma Joachim Ganzer KG staff or staff at the trial sites.
10. any relationship of dependence with the sponsor and/or with the investigator.
11. Mentally disabled patients
12. Institutionalised due to an official or judicial order.
Immunotherapy criteria:
13. Previous specific immunotherapy with grass pollen in any formulation.
14. Any current immunotherapy.
15. Any previous specific immunotherapy with unknown allergen or an unsuccessful immunotherapy.
Other allergies:
16. A skin prick test or RAST result to the other tested allergens with > Timothy grass pollen allergens and/or 6-grasses pollen allergen mixture.
• Sensitisation to dog epithelia (skin prick test > Timothy grass pollen allergens and/or 6-grasses pollen allergen mixture) is acceptable, if the patient has no direct contact to dogs and / or
• Sensitisation to cat epithelia (RAST ≥ 0.70kU/L) epithelia is acceptable, if the patient has no direct contact to cats.
Diseases and health status:
17. Clinically relevant rhinoconjunctival or respiratory symptoms related to other reasons (e.g. vasomotor or rhinitis medicamentosa).
18. PEF < 80% (GINA grade III or IV) of predicted normal (ECSC).
19. Uncontrolled or partly controlled asthma according to GINA guidelines (version 2006).
20. Perennial and continuously treated asthma.
21. Rhinoconjunctival atopic symptoms for 20 years or longer.
22. Severe acute or chronic diseases that would affect the study objectives or patient safety (e.g., Diabetes mellitus type I, malignant neoplasia, chronic renal failure), coronary heart diseases, severe inflammatory diseases (e.g. liver, kidneys).
23. Autoimmune diseases, immune-defects including immune-suppression, immune-complex-induced immunopathies (e.g. HIV, post-transplant patients, multiple sclerosis (MS), active tuberculosis, lupus erythematodes [SLE], Grave’s disease, Hashimoto’s thyroiditis) at time of screening.
24. Any clinically significant (as determined by the investigator) psychiatric and psychological disorders including impairment of cooperation (e.g. alcohol or drug abuse).
25. Recurrent seizures.
26. Irreversible secondary alterations of the reactive organ (e.g. emphysema, bronchiestasis).
27. For patients consent for the visit in the environmental challenge chamber (ECC): An anatomic abnormality that interferes with assessment of Total Nasal Symptom- -Score (TNSS).
28. Atopic dermatitis or other dermatological abnormalities (e.g. Naevi, tattoos, scars, etc.) contraindicating intracutaneous testing.
29. A negative reaction of the positive control after 15 minutes in the pre-treatment ICT.
30. A local swelling area of the fore arm beyond the wrist and elbow as result of the LPR of the ICT with the lower of the two applied doses on visit S2.
31. Laboratory values beyond Grade 1 according to the FDA Guidance for Industry (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) without a medically plausible comment by investigator as not clinically relevant.
Medications:
32. Treatment with beta-blockers (locally and systemically).
33. Contraindication for adrenalin (e.g. acute or chronic symptomatic coronary heart disease, severe hypertension).
34. Completed or ongoing treatment with anti-IgE-antibody (Xolair®).
35. Long-term treatment with tranquilizer or other psychoactive drugs.
36. Any medication (e.g. oral antihistamines, etc.) that could interfere with the skin reaction has to be stopped before performing the skin tests (SPT and ICT) according their half-life. Use of any short acting antihistamines (e.g. diphenhydramine) within 2 days, or long-acting antihistamines (e.g. fexofenadine, ceterizine, loratadine or desloratadine) within 7 days prior to skin testing.
37. For patients with controlled asthma: Treatment with inhaled corticosteroids with a daily dose > 500µg BDP or equivalents.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The change of the size of the swelling (area in mm²) 6 hours after intracutaneous testing (Late Phase Reaction) between baseline (visit S2) and after treatment (visit FU2). Therefore, the size of the swelling area measured after application of the individual optimal concentration (determined during visit S2) will be subtracted. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Efficacy:
• Change of the Total Nasal Symptom Score (TNSS) as measured in the ECC between baseline and after end of treatment.
• Change from baseline in specific total IgG and IgG4 and at the end of treatment.
• Change of the amount of nasal secretion in the ECC between baseline and after end of treatment.
Safety
Safety of treatment during the entire trial period will be assessed by
• Adverse events (AE) overall and systemic AEs.
• Size of local reactions (diameter in mm) at the injection site 30min after drug administration.
• Clinical laboratory tests (hematology, clinical chemistry and urinalysis).
• Vital signs (resting blood pressure, pulse rate and respiratory rate).
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
