Dose-Finding Study Clinical Trial
Official title:
A Randomised, Double-Blind, Parallel Group, Multicentre Study to Assess the Efficacy and Safety of Four Concentrations of Depigoid® Phleum in Patients With Allergic Rhinitis and/or Rhinoconjunctivitis With or Without Intermittent Asthma
Specific immunotherapy for IgE mediated sensitization to grass pollen
4 concentrations of a modified pollen extract of Phleum pratense are applied to find out the
optimum dose.
| Status | Completed |
| Enrollment | 308 |
| Est. completion date | June 2013 |
| Est. primary completion date | April 2013 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 70 Years |
| Eligibility |
Inclusion Criteria: - appropriately signed and dated ICON prior to study specific action - IgE-mediated Sensitization against grass pollen - Perception of disease activity of at least 30 mm on a 100 mm VAS - FEV1 or a PEFR value > 80% of predicted normal value - Allergic rhinitis and/or rhinoconjunctivitis symptoms (at least 2 years) with or without intermittent asthma symptoms verified by: - suggestive medical history AND - specific IgE against grass pollen with CAP-RAST = 2 AND - a positive SPT (wheal diameter = 3 mm) AND - a positive CPT for grass pollen - Patients with co-allergies are allowed to enter the study: - being asymptomatic against co-allergens such as tree or weed pollen, house dust mites, cat and dog, and other country specific allergens - with CAP-RAST co-allergen < grass (detailed specifications given for Birch, HDM, animal dander, other country specific allergens) - All other co-allergens: difference in CAP RAST co-allergen to grass of = 2 and an SPT wheal diameter co-allergen < grass - Females of non-childbearing potential must be postmenopausal for at least 1 year or surgically sterilized - Females of childbearing potential must be non-lactating, non-pregnant and must correctly use an effective method of contraception during the study. Exclusion Criteria: - Acute or chronic infectious conjunctivitis - History of significant clinical manifestations of allergy as a result of sensitisation against trees or weed pollen and perennial allergens (e.g., house dust mites) Patients are not allowed to enter into the study: - with typical symptoms against co-allergens such as tree or weed pollen, HDM, cat and dog, and other country specific allergens - with CAP-RAST co-allergen = grass - Persistent asthma, according to Global Initiative for Asthma (GINA) - Acute or chronic inflammatory or infectious airways disease - Chronic structural disease of the lung (e.g., emphysema or bronchiectasis) - Autoimmune and/or immune deficiency - Any disease that prohibits the use of adrenaline (e.g., hyperthyroidism) - Severe uncontrolled disease that could increase the risk to the patients while participating in the study, including but not limited to: cardiovascular insufficiency, severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases or haematological disorders. - Active malignant disease during the previous 5 years - Significant abnormal laboratory parameter or alteration in vital signs that could increase the risk to the study patient - Abuse of alcohol, drugs or medications within the past year - Severe psychiatric, psychological or neurological disorder - Immunotherapy against grass pollen within the last 5 years - Systemic and/or topical treatment with ß-blockers within 1 wk prior to V2 - Use of medication that may interfere with the immune system or has been using any medication which might still have an influence on the immune system at V2 - Use of tranquiliser or psychoactive drugs within 1 week prior to V1 - Use of systemic corticosteroids within 3 months prior to V1 - Immunization with vaccines within 7 days prior to V2 - Expected non-compliance and/or no cooperation - Participation in another clinical study within 30 days prior to V2 - Prior participation in this study - Employees at the investigational centre or first degree relative or partner of the investigator - Planed donation of germ cells, blood, organs or bone marrow during the course of the study - Contractually not capable - A positive pregnancy test at V1 - Jurisdictional or governmentally institutionalised. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
| Country | Name | City | State |
|---|---|---|---|
| Germany | Hippke, Ear-Nose-Throat specialist | Berlin | |
| Germany | Zentrum für Rhinologie und Allergie | Wiesbaden |
| Lead Sponsor | Collaborator |
|---|---|
| Leti Pharma GmbH |
Germany,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Conjunctival Provocation Test (CPT) | Comparison between dosage groups: percentage of patients who need an increased amount of allergen to provoke a positive CPT at the end of the treatment (comparison slope of efficacy). It is expected that at the end of the study higher doses are necessary to provoke a positive CPT. According to the EMA "Guideline on clinical development of products for specific immunotherapy for the treatment of allergic diseases" provocation tests are accepted as primary outcomes for dose-finding studies. |
At screening and after approx. 22 weeks (EoS) | No |
| Secondary | Conjunctival Provocation Test (CPT) | Analysis of individual results for allergen amount | after approx. 22 weeks (EoS) | No |
| Secondary | Overall assessment of safety (tolerability) at the end of the study | At the end of the study investigator and patient will give their general overall impression on the safety of the study treatment on a 4-point scale (excellent, good, moderated, unacceptable). Results will be compared between dosage groups |
after approx. 22 weeks (EoS) | Yes |
| Secondary | Number of Participants with Adverse Events as a Measure of Safety and Tolerability | AEs are recorded at the study visits (patients are questioned and the patient diary - where specific allergic symptoms should be recorded by the patients during 48hrs after each injection of IMP - is assessed by the investigator and AEs recorded in the CRF if applicable) and at any time of the study when site becomes aware of an Ae/SAE. AE/SAE rate is compared between treatment groups (safety profile. Also rates of local and systemic reactions will be calculated. |
at 4-weekly intervals (retrospectively at study visits) | Yes |
| Secondary | Patient diary: Allergy specific symptoms and concommitant medication (rescue m.) for 48hrs after application of IMP | Symptoms: - at injection site, - of the skin (not injection site), - of the nose, - of the eyes, - of the lung/respiratory system, other symptoms Symptoms documented in the diary will be judged and assessed by the investigator and - if applicable - transcribed as AE into the CRF. Medication: Antihistaminics (eye drops, nose spray or tablet), Sultanol, oral corticosteroid and intake of other medication documented in the diary are to be transcribed to the CRF |
48hrs every 4 weeks after each application of IMP | Yes |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
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