Evaluation of the Efficacy of Allergen-specific Immunotherapy Using Assessment in an Allergen Exposure Chamber-a Randomized Placebo-controlled Double-blind Study (RANSES)
A Randomized Placebo-controlled Double-blind Clinical Study for Evaluation of the Efficacy of Allergen-specific Immunotherapy Using Clinical and Biomarker Assessment in an Allergen Exposure Chamber and During Natural Exposure in Patients with House Dust Mite-triggered Allergic Rhinoconjunctivitis RANSES
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This clinical trial will be performed as a randomized, double-blind, placebo-controlled phase IV study in adult patients. Thus, 2 parallel groups, one active treated and one placebo group, will be investigated. Patients from 18 to 65 years of age with moderate to severe allergic rhinitis or rhinoconjunctivitis to HDM allergens, with or without controlled allergic bronchial asthma, will be enrolled.
The efficacy will be evaluated using an AEC (TNSS) and additionally in the patient's natural environment (SMS). The screening phase will begin approximately in May and last until September 2024. All patients fulfilling the eligibility criteria at Screening Visit 1 (S1) will perform an AEC visit (AEC-pre) in October, followed by an e-Diary phase in November, December (Diary-pre). For the assessment of the pre-treatment score 4 consecutive weeks will be recorded and at least 2 consecutive weeks with complete daily entries must available. Adequate symptoms are defined as patient randomization criteria in the respective section of the synopsis/protocol. After randomization, patients will be treated for approximately 10 months. Afterwards a second Diary phase (Diary-post) will be performed. For the assessment of the post-treatment score, at least 2 consecutive weeks with complete daily entries must be available. Then, a second, posttreatment challenge (AEC-post) will follow. Last patient last visit is planned for January 2026. For the trial approximately 80 male and female outpatients (18 to 65 years of age) will be screened, and 67 patients will be randomized 1:1 verum/placebo. It is assumed, that this number of patients will yield a total of at least 60 patients with available post-treatment assessments, assuming a dropout rate of 10%. Additionally, data from 11 healthy subjects from a previous study with an identical setting will be included in the correlation analysis. There will be no replacement strategy employed for patients dropping out prematurely.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Marek M Jutel, prof.
- Phone Number: +48731021221
- Email: marek.jutel@all-med.wroclaw.pl
Study Contact Backup
- Name: Magdalena E Zemelka-Wiacek, Dr
- Phone Number: +48507019921
- Email: magdalena.zemelka-wiacek@umw.edu.pl
Study Locations
-
-
DL
-
Wroclaw, DL, Poland, 53-201
- Recruiting
- ALL-MED Medical Research Institute
-
Contact:
- Magdalena E Zemelka-Wiacek, Dr
- Phone Number: +48507019921
- Email: magdalena.zemelka-wiacek@umw.edu.pl
-
Contact:
- Agnieszka Chuda, Msc
- Phone Number: +48791340019
- Email: agnieszka_chuda@wp.pl
-
Contact:
- Marek M Jutel, Professor
-
Contact:
- Anna Kosowska, Dr
-
Contact:
- Magdalena E Zemelka-Wiacek, Dr
-
Contact:
- Monika Rosa, Dr
-
Contact:
- Magdalena Prosciak, Dr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
To be eligible for trial participation, patients must meet all the following inclusion criteria:
- Written informed consent given from patient according to local requirements before any trial-related activities started (a trial-related activity is any procedure that would not have been performed during the routine management of the patient)
- Legally competent male or female outpatient between 18 and ≤ 65 years
IgE-mediated moderate to severe allergic rhinitis or rhinoconjunctivitis with or without allergic asthma caused by HDM allergens documented by
Positive Skin prick test (SPT) result to D. pteronyssinus allergens:
D. pteronyssinus test solution (wheal diameter) ≥ 3 mm and Positive histamine-control reaction (wheal diameter) ≥ 3 mm and Negative NaCl-control reaction (wheal diameter) < 2 mm Immunoassay result for specific IgE ≥ 0.70 kU/L to D. pteronyssinus
- Symptoms of rhinitis or rhinoconjunctivitis e.g., during the months October to February or over the entire year for at least 2 years before enrolment.
- Assessment of persistent, moderate-severe rhinitis acc. to ARIA guidelines (Brozek et al.
2017, Bousquet et al. 2001) Symptoms for 4 or more consecutive weeks in the previous years and for at least 4 days per week during those weeks More than one of the symptoms evaluated as "troublesome" by the patients and/or impairing their daily activities, leisure or sport, school, or work and/or involving sleep disturbance 6. Symptoms requiring regular intake of anti-symptomatic medication 7. Previous symptomatic anti-allergic medication for at least 2 seasons prior to enrolment 8. At entry to this trial: No diagnosis of bronchial asthma in medical history or confirmed diagnosis of asthma as being "well controlled" according to GINA recommendation (GINA 2022)
Exclusion Criteria:
General criteria:
- Patients are unable to understand and comply with the requirements of the trial, as judged by the investigator
- Currently participating in another clinical trial or participating in any other clinical trial within 30 days prior informed consent for this trial
- Low adherence to trial procedures expected or inability to understand instructions/trial documents
- Involvement in the planning and conduct of the trial
- Any relationship of dependence with the investigator
- Previous randomization to treatment in the present trial
- Mentally disabled
- Institutionalized due to an official or judicial order For female patients with childbearing potential (i.e., females who are not chemically or surgically sterilized or females who are not post-menopausal)
- Positive urine pregnancy test or pregnant
- Wish to become pregnant during the course of the trial
- Not using highly effective and reliable contraception, as judged by the investigator (reliable and highly effective methods of birth control defined as a failure rate of less than 1% per year [CTFG recommendations 2020]) during the trial. Sexual abstinence is an allowed method of birth control (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.) Males are not required to use any contraception during the study.
Wish to breastfeed or breastfeeding
Immunotherapy criteria:
- History of a confirmed anaphylaxis after an AIT injection
- Current treatment with any kind of AIT
- AIT with HDM allergoids or allergens within the last 5 years
- AIT with unknown allergen within the last 5 years Sensitization criteria
Clinically relevant symptoms to perennial and seasonal allergens which interfere with the assessment period of October to January. Exceptions are symptoms to allergens of cat and dog, if the patient has no direct contact to these animals.
Diseases and health status:
- Clinically relevant chronic rhinoconjunctival or respiratory symptoms related to other reasons than allergy
- Chronic persistent rhinitis symptoms for 20 years or longer
- Forced expiratory volume in 1 second (FEV1) < 70 % of predicted normal values according to Quanjer (Quanjer et al. 2012) under adequate asthma treatment according to GINA recommendation (GINA 2022)
- Uncontrolled or partly controlled asthma according to GINA recommendation (GINA 2022)
- Asthma exacerbation within the last 6 months prior to randomization defined as unscheduled doctors visit, hospitalization, or emergency unit visit requiring the use of systemic corticosteroids or change of controller medication
- Severe acute or chronic diseases (e.g., COVID-19, chronic urticaria, mastocytosis, active tuberculosis, diabetes mellitus type I, malignant neoplasia, chronic renal failure), severe inflammatory diseases (liver, kidneys)
- Autoimmune diseases, immune defects including immunosuppression, immune-complexinduced immunopathies (e.g., HIV, post-transplant patients, lupus erythematodes [SLE], vitiligo, Grave's disease, multiple sclerosis)
- Severe psychiatric and psychological disorders including impairment of cooperation (e.g., alcohol or drug abuse)
- Recurrent seizures (e.g., febrile convulsion, untreated epilepsy)
- Irreversible secondary alterations of the reactive organ (e.g., emphysema, bronchiectasis)
For assessment the normal reference ranges of the central laboratory should be applied. If out of range, laboratory values greater than grade 1 according to the FDA Guidance for Industry (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) will lead to exclusion of the patient.
Medications:
- Use of β-blockers (locally or systemically) and/or angiotensin-converting enzyme (ACE) inhibitors
- Contraindication for use of adrenalin (e.g., acute, or chronic symptomatic coronary heart disease, severe hypertension)
- Completion or ongoing treatment with anti-IgE-antibodies (e.g., omalizumab) or anti IL4/IL13 antibodies (e.g., dupilumab) or other biological medication interfering with the TH2 pathway
- Completed or ongoing long-term treatment with tranquilizer or other psychoactive drugs
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: verum
Immunotherapy - NovoHelisen Depot according to desensitisation protocol 5 times weekly increasing injections 250-5000 TU, 10 times monthly maintenance injections 5000 TU
|
allergen immunotherapy treatment for 12 months with house dust mite allergen preparation
|
|
Placebo Comparator: placebo
5 times weekly increasing placebo injections, 10 times monthly placebo injections
|
allergen immunotherapy treatment for 12 months with house dust mite allergen preparation
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Total nasal symptom score
Time Frame: 12 months
|
The primary efficacy analysis is the analysis of correlation between TNSS recorded in the AEC and the average CSMS over 2 weeks as recorded in the eDiary.
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change of the TNSS
Time Frame: 12 months
|
Change of the TNSS at 120 minutes recorded in the AEC from pre-treatment to post treatment, calculated as post treatment TNSS - pre-treatment TNSS, and Change in average CSMS from pre-treatment to post-treatment calculated as post treatment CSMS - pre-treatment CSMS
|
12 months
|
|
Change in average CSMS
Time Frame: 12 months
|
Change in average CSMS from pre-treatment to post-treatment calculated as post treatment CSMS - pre-treatment CSMS
|
12 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Agnieszka M Chuda, MSc, All-Med Specjalistyczna Opieka Medyczna. Medyczny Instytut Badawczy
Publications and helpful links
General Publications
- Jutel M, Zemelka-Wiacek M, Okamoto Y, Pfaar O. Algorithms in Allergy: Assessment of Rhinitis Using Allergen Exposure Chambers. Allergy. 2024 Dec 17. doi: 10.1111/all.16444. Online ahead of print. No abstract available.
- Zemelka-Wiacek M, Kosowska A, Jutel M. Symptom Assessment of Patients with Allergic Rhinitis Using an Allergen Exposure Chamber. J Vis Exp. 2023 Mar 3;(193). doi: 10.3791/64801.
- Zemelka-Wiacek M, Kosowska A, Winiarska E, Sobanska E, Jutel M. Validated allergen exposure chamber is plausible tool for the assessment of house dust mite-triggered allergic rhinitis. Allergy. 2023 Jan;78(1):168-177. doi: 10.1111/all.15485. Epub 2022 Sep 1.
- Kosowska A, Zemelka-Wiacek M, Smolinska S, Wyrodek E, Adamczak B, Jutel M. Clinical validation of grass pollen exposure chamber in patients with allergic rhinitis triggered by timothy grass. Clin Exp Allergy. 2024 Jul;54(7):489-499. doi: 10.1111/cea.14482. Epub 2024 Apr 14.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ALL-MED
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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