Dose Finding Study Depigoid Phleum: 4 Doses in Patients With Allergic Rhinitis/Rhinoconjunctivitis +-Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Leti Pharma GmbH
ClinicalTrials.gov Identifier:
NCT01634958
First received: July 3, 2012
Last updated: November 18, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Allergic Rhinitis/Rhinoconjunctivitis +- Intermittent Asthma
Sensitization Against Phleum Pratense Pollen
Dose-Finding Study
Biological: Depigoid Phleum
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
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

Resource links provided by NLM:


Further study details as provided by Leti Pharma GmbH:

Primary Outcome Measures:
  • Conjunctival Provocation Test (CPT) [ Time Frame: At screening and after approx. 22 weeks (EoS) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Conjunctival Provocation Test (CPT) [ Time Frame: after approx. 22 weeks (EoS) ] [ Designated as safety issue: No ]
    Analysis of individual results for allergen amount

  • Overall assessment of safety (tolerability) at the end of the study [ Time Frame: after approx. 22 weeks (EoS) ] [ Designated as safety issue: Yes ]

    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


  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: at 4-weekly intervals (retrospectively at study visits) ] [ Designated as safety issue: Yes ]

    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.


  • Patient diary: Allergy specific symptoms and concommitant medication (rescue m.) for 48hrs after application of IMP [ Time Frame: 48hrs every 4 weeks after each application of IMP ] [ Designated as safety issue: Yes ]

    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



Enrollment: 308
Study Start Date: October 2012
Study Completion Date: June 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 10.000 DPP/ml suspension for s.c. inj. Biological: Depigoid Phleum
Suspension for subcutaneous injection Build-up phase (day 1): 0,1mL + 0,2mL + 0,2mL s.c.injections in intervals of 30 minutes Maintenance phase: 5x single s.c. injection of 0,5mL every 4 weeks
Other Names:
  • Depigoid (R) Phleum
  • Depigmented and glutaraldehyde polymerized extract of 100% phleum pratense pollen adsorbed onto aluminium hydroxide)
Experimental: 5.000 DPP/ml suspension for s.c. inj. Biological: Depigoid Phleum
Suspension for subcutaneous injection Build-up phase (day 1): 0,1mL + 0,2mL + 0,2mL s.c.injections in intervals of 30 minutes Maintenance phase: 5x single s.c. injection of 0,5mL every 4 weeks
Other Names:
  • Depigoid (R) Phleum
  • Depigmented and glutaraldehyde polymerized extract of 100% phleum pratense pollen adsorbed onto aluminium hydroxide)
Experimental: 1.000 DPP/ml suspension for s.c. inj. Biological: Depigoid Phleum
Suspension for subcutaneous injection Build-up phase (day 1): 0,1mL + 0,2mL + 0,2mL s.c.injections in intervals of 30 minutes Maintenance phase: 5x single s.c. injection of 0,5mL every 4 weeks
Other Names:
  • Depigoid (R) Phleum
  • Depigmented and glutaraldehyde polymerized extract of 100% phleum pratense pollen adsorbed onto aluminium hydroxide)
Experimental: 100 DPP/ml suspension for s.c. inj. Biological: Depigoid Phleum
Suspension for subcutaneous injection Build-up phase (day 1): 0,1mL + 0,2mL + 0,2mL s.c.injections in intervals of 30 minutes Maintenance phase: 5x single s.c. injection of 0,5mL every 4 weeks
Other Names:
  • Depigoid (R) Phleum
  • Depigmented and glutaraldehyde polymerized extract of 100% phleum pratense pollen adsorbed onto aluminium hydroxide)

Detailed Description:

This is a dose finding study and no therapeutic study. Patients will receive in 4-weekly intervals 6x 0,5mL of one of 4 different concentrations of Depigoid Phleum. The study is performed outside the pollen season. Thus the aim of the study is not the therapeutic effect of the specific immunotherapy (effect on allergy specific symptoms during the pollen season) but the effect on the Conjunctival provocation test (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.

For the CPT increasing doses of Phleum pollen solutions are applied to the eye and characteristic symptoms (eye redness, weeping, itching or burning, and nose dripping/blockage) are assessed at each concentration: 0=absent, 1=mild, 2=moderate, 3=severe. At a score value of >=5/concentration the test is considered positive and finished.

It is expected that at the end of the study higher doses are necessary to provoke a positive CPT.

Furthermore comparative evaluation of the safety data (AEs) in the different dosage groups is a very important parameter for the evaluation of the outcome of the study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 β-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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01634958

Locations
Germany
Hippke, Ear-Nose-Throat specialist
Berlin, Germany, 10117
Zentrum für Rhinologie und Allergie
Wiesbaden, Germany, 65183
Sponsors and Collaborators
Leti Pharma GmbH
Investigators
Principal Investigator: Oliver Pfaar, PD Dr. med. Centre for Rhinology and Allergology of University Hospital Mannheim
Study Director: Angelika Sager, Dr. med. Leti Pharma GmbH
  More Information

No publications provided

Responsible Party: Leti Pharma GmbH
ClinicalTrials.gov Identifier: NCT01634958     History of Changes
Other Study ID Numbers: 6043-PG-PSC-192, 2012-000416-28
Study First Received: July 3, 2012
Last Updated: November 18, 2013
Health Authority: Germany: Paul-Ehrlich-Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Czech Republic: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Leti Pharma GmbH:
Allergic Rhinitis
Hayfever
Immunotherapy
Dose-Finding-Study

Additional relevant MeSH terms:
Asthma
Rhinitis
Signs and Symptoms
Conjunctivitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Conjunctival Diseases
Eye Diseases
Aluminum Hydroxide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014