Subcutaneous Administration of Mannan-Conjugated Birch Pollen Allergoids in Adolescents and Adults with Birch Pollen-Induced Allergic Rhinitis or Rhinoconjunctivitis
- Trial ID
- 2024-515717-17-00
- Protocol
- T502-SIT-073
- Sponsor
- Inmunotek S.L.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this trial is to evaluate the clinical impact of **T502** treatment, administered subcutaneously, on individuals with birch pollen-induced allergic rhinitis or rhinoconjunctivitis. The clinical relevance of this objective lies in its potential to improve symptom management and reduce medication dependency during the peak birch pollen season. The trial will compare the symptoms and medication needs between participants receiving the active treatment and those receiving a placebo.
Participants
The clinical trial involves participants diagnosed with **birch pollen-induced allergic rhinitis** or rhinoconjunctivitis. The study population includes both male and female subjects, aged between 12 and 64 years, with at least 10% of the participants being adolescents aged 12 to 17. Participants are required to be in good physical and mental health and must have a confirmed diagnosis of birch pollen allergy, evidenced by a medical history of moderate to severe symptoms for at least two previous seasons, a positive skin prick test, and specific IgE levels against birch pollen allergens. The trial includes individuals with controlled asthma, as per the Global Initiative for Asthma guidelines, and requires normal renal and liver function. Females of childbearing potential must adhere to effective contraception methods and have a negative pregnancy test at screening. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed as a **prospective, randomized, double-blind, placebo-controlled** multicenter study. The primary objective is to assess the clinical impact of T502 treatment, specifically a **mannan-conjugated birch pollen allergoid**, administered subcutaneously to participants with birch pollen-induced allergic rhinitis or rhinoconjunctivitis. The trial will compare the symptoms and medication needs between actively treated participants and those receiving a placebo during the peak birch pollen season. The trial is expected to commence recruitment on November 4, 2024, and conclude by June 13, 2025, with a total duration of approximately 19 months.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, health status, and a confirmed diagnosis of birch pollen allergy. This visit will include laboratory tests to assess specific IgE levels and ensure normal renal and liver function. Female participants of childbearing potential will undergo a pregnancy test. Following the screening, participants will be randomized to receive either the active treatment or placebo. Subsequent visits will be scheduled to monitor the participants' health, adherence to the treatment protocol, and any adverse events. The end-of-study visit will evaluate the primary endpoint, which is the mean daily Combined Symptom and Medication Score (CSMS) over the peak birch pollen season in 2025.
Participant involvement is expected to last for the entire duration of the trial, approximately 19 months, unless early termination is warranted. Conditions for early termination include significant adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial will ensure that at least 10% of the participant population is aged 12-17 years, and all participants must provide informed consent. The study will adhere to ethical guidelines and regulatory requirements to ensure participant safety and data integrity throughout the trial.
Treatment
The clinical trial involves the administration of **mannan-conjugated allergoid (polymerized) Betula pendula parenteral vaccine**. This investigational medicinal product is provided as a solution for injection, specifically designed for subcutaneous administration. The active substance, **Betula pendula pollen allergoid**, is mannan-conjugated and polymerized, classified as a structurally diverse substance - allergen. The maximum daily dose is 10,000 units, with a total maximum dose of 28,000 units over a treatment period of 19 weeks. Participant compliance is monitored through scheduled visits and dose administration records.
In addition to the experimental treatment, a **placebo** is utilized in the study. The placebo is identical in appearance to the investigational medicinal product and is administered via subcutaneous injection. The placebo serves as a control to evaluate the efficacy of the experimental treatment. The administration schedule and monitoring for the placebo group mirror those of the active treatment group to maintain the study's double-blind design.
Participants may also receive standard-of-care treatments, including **Budes 64 Mikrogramm/Sprühstoß Nasenspray, Suspension**. This nasal spray contains **budesonide** as the active ingredient, delivered as a suspension. The maximum daily dose is 256 micrograms, with a total maximum dose of 7,168 micrograms over a 4-week period. The nasal spray is administered as needed to manage symptoms, and compliance is tracked through participant diaries and periodic assessments.
Another auxiliary treatment is **NASACORT 55 Mikrogramm/Dosis Nasenspray, Suspension**, containing **triamcinolone acetonide**. This nasal spray is also a suspension, with a maximum daily dose of 220 micrograms and a total maximum dose of 6,160 micrograms over 4 weeks. It is administered nasally, and participant adherence is monitored similarly to other treatments.
**Flutica-Teva® 50 Mikrogramm Nasenspray, Suspension** is another nasal spray option, containing **fluticasone propionate**. The maximum daily dose is 160 micrograms, with a total maximum dose of 4,480 micrograms over 4 weeks. Administration and compliance monitoring follow the same protocol as other nasal sprays in the study.
For ophthalmic use, **Livocab® direkt Augentropfen 0,05 % Augentropfen, Suspension** is available, containing **levocabastine hydrochloride**. The maximum daily dose is 0.06 milligrams, with a total maximum dose of 1.68 milligrams over 4 weeks. These eye drops are administered as needed, with compliance tracked through participant logs and clinical evaluations.
**Azelastin COMOD 0,5 mg/ml Augentropfen, Lösung** is another ophthalmic treatment, containing **azelastine hydrochloride**. The dosing schedule and compliance monitoring are consistent with other eye drop treatments, with a maximum daily dose of 0.06 milligrams and a total maximum dose of 1.68 milligrams over 4 weeks.
Oral treatments include **Desloratadin Glenmark 5 mg Tabletten**, containing **desloratadine**. The maximum daily dose is 5 milligrams, with a total maximum dose of 140 milligrams over 4 weeks. Tablets are taken orally, and adherence is monitored through participant reports and pill counts.
**Allegra Allergietabletten 20 mg Tabletten**, containing **bilastine**, is another oral option. The maximum daily dose is 20 milligrams, with a total maximum dose of 560 milligrams over 4 weeks. Compliance is tracked similarly to other oral treatments.
Additional treatments include **AVAMYS 27.5 micrograms/spray, nasal spray suspension**, containing **fluticasone furoate**, and **Mometason ratiopharm 50 Mikrogramm/Sprühstoß Nasenspray, Suspension**, containing **mometasone furoate**. Both are administered nasally, with compliance monitored through participant diaries and clinical assessments.
For skin-prick testing, solutions such as **HAL Allergy Prick Test Hundeepithelien** and **HAL Allergy Prick Test Hausstaubmilbe Dermatophagoides Pteronyssinus** are used. These solutions contain structurally diverse substances - allergens, administered subcutaneously for diagnostic purposes. Compliance and administration are documented during clinical visits.
Other treatments include **Levocetirizin-ratiopharm 5 mg Filmtabletten**, **Alvesco 160 Mikrogramm Druckgasinhalation, Lösung**, and **Rupatadin AL 10 mg Tabletten**, each with specific dosing schedules and compliance monitoring protocols. These treatments are administered orally or via inhalation, with adherence tracked through participant logs and clinical evaluations.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the clinical impact of the T502 treatment, which is administered subcutaneously to participants with birch pollen-induced allergic rhinitis or rhinoconjunctivitis. The primary endpoint for efficacy assessment is the mean daily Combined Symptom and Medication Score (CSMS) over the peak birch pollen season in 2025. This score will be compared between the placebo group and the active treatment group to determine the treatment's effectiveness.
The CSMS is a comprehensive measure that combines both symptom severity and medication usage, providing a holistic view of the treatment's impact on the participants' condition. The data collection for this endpoint will occur during the peak birch pollen season, ensuring that the assessment captures the period of highest allergen exposure and potential symptom manifestation. The analysis will focus on the differences in CSMS between the two groups, offering insights into the treatment's ability to alleviate symptoms and reduce medication dependency.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants aged from 12 to 64 years (at least 10% of the population should be 12-17 years of age)
- Signed and dated Informed Consent Form , a. by a legally competent participant, b. For adolescents: self-completed (signed and dated) informed consent to participate in the trial and signed and dated Informed Consent Form by both parents/legal guardian(s)
- Being in good physical and mental health.
- Having the diagnosis of birch pollen allergy based on all the following criteria: a. A medical history of moderate to severe allergic rhinitis or rhinoconjunctivitis due to birch pollen allergens for at least 2 previous seasons (definition of allergy severity according to ARIA), b. Being treated with anti-allergic medication for at least 2 birch pollen seasons prior to enrolment, c. A positive skin prick test (SPT - wheal diameter ≥3 mm) to birch pollen allergens, positive control (histamine) wheal ≥3 mm, negative control (NaCl) wheal <2 mm.
- Females: a. With childbearing potential (a woman is considered of childbearing potential [WOCBP] according to the CTFG, if she is i.e., fertile, following menarche and until becoming postmenopausal unless becoming permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must be willing to use a highly effective method of contraception: • Oral, intravaginal or transdermal hormonal medical drugs or -devices containing oestrogen/progesterone combinations. • Oral, injectable or implantable hormonal medical drugs or -devices containing progesterone-only. • Intrauterine device (IUD); • Intrauterine hormone-releasing system (IUS); • Bilateral tubal occlusion; • Vasectomized partner (provided that partner is the sole sexual partner of the WOCB trial participant and that the vasectomized partner has received medical assessment of the surgical success); • Sexual abstinence (Defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial 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 participant). b. Females unable to bear children (i.e., pre-menarche, tubal ligation, hysterectomy, or post-menopausal (a postmenopausal state is defined as no menses for 12 months without an alternative medical cause).
- For asthmatic participants: confirmed diagnosis of controlled asthma during the treatment period according to Global Initiative for Asthma (GINA) guidelines (steps 1-3, GINA 2023).
- FEV1 ≥80% of the participant’s reference value or Peak Expiratory Flow (PEF) ≥80% of the participants´ individual optimal value (for asthmatic participants only) measured at the screening visit.
- Laboratory tests: a. Specific IgE against birch pollen allergens (common silver birch t3, minimum CAP class 3 or higher, ≥3.5 kU/L); in case that the IgE CAP-class is =2, the participant can be included, when a previous lab report (not older than 2 years and measurement outside the birch pollen season) states that the participant has CAP class 3 or higher), b. Confirmed normal renal and liver function, including non-clinically significant deviations outside the reference ranges (< grade 2 according to the FDA Guidance for Industry for preventive Vaccine Trials [FDA 2007] at screening visit. Participants with laboratory values ≥ grade 2 will require retesting before inclusion in the trial. Upon normalization of the out-of-range value(s), the participant can be included in the trial), c. Female participants with childbearing potential must have a negative pregnancy test in serum at screening.
Exclusion Criteria
- Simultaneous participation in other clinical trials or previous participation within 30 days before inclusion.
- Previous immunotherapy with birch pollen allergens within the last 5 years.
- Ongoing immunotherapy with birch pollen allergens or any other allergens
- Participants with acute allergic rhinitis or rhinoconjunctivitis due to other environmental allergens during the trial period.
- Being in any relationship or dependence with the Sponsor, CRO and/or Investigator.
- Inability to understand instructions/trial documents.
- Participants for whom the Investigator believes that they will not comply with the protocol (participants with known alcohol or drug abuse or with a history of a serious psychiatric disorder as well as participants unwilling to give informed consent or to abide by the requirements of the protocol).
- Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
- Participants who do not have access to a smartphone/tablet (iOS or Android, in exceptional cases, a paper diary may be issued if installation on the mobile device is not technically possible).
- History of systemic reactions and/or anaphylaxis (Grade III or IV according to the AWMF guideline 2021), including to food (e.g., peanut, marine animals) or to Hymenoptera venom (e.g., bee, wasp stings) or to medication (e.g., penicillin), etc.
- History of hypersensitivity to the excipients of the investigational product or placebo.
- Mild persistent to severe persistent asthma, partly controlled or uncontrolled asthma according to GINA guidelines (GINA 2023) during the treatment period.
- Chronic asthma or emphysema, particularly with a Forced Expiratory Volume in 1 second (FEV1) <80% of the participant’s reference value (ECSC) or Peak Expiratory Flow (PEF) <80% of the participants’ individual optimal value measured at the screening visit.
- Previous or ongoing respiratory tract infection (e.g., flu, COVID-19) and/or exacerbation of asthma within 4 weeks before the screening visit.
- History of significant renal disease or chronic hepatic disease.
- Malignant active disease (ongoing or within the five past years).
- Severe autoimmune disease.
- Immune defects including immunosuppression, immunopathies.
- Vaccination during the entire treatment period, except flu and SARS-CoV-2 vaccinations.
- Use of systemic immunosuppressive medications (e.g., methotrexate or cyclosporine A) or blood transfusion from one month before screening until the end of the trial.
- General inflammatory, severe acute or chronic inflammatory diseases.
- Other chronic diseases such as severe congestive heart failure, cardiovascular insufficiency, active gastric ulcer, inflammatory bowel disease, uncontrolled diabetes mellitus, etc.
- Intake of antidepressant drugs with potent antihistamine properties such as tricyclic antidepressants (e.g., doxepin, amitriptyline, desipramine, imipramine, etc.).
- Administration or planned administration of anti-IgE antibodies, mast cell stabilizers or anti-leukotriene agents.
- Intake of beta-blockers/ACE inhibitor medication (angiotensin-converting enzyme inhibitor).
- Active tuberculosis.
- Having any contraindication for the use of adrenaline (including hyperthyroidism).
- Known positive serology to Human Immunodeficiency Virus-1/2, Hepatitis B Virus or Hepatitis C Virus.
- Females who are pregnant, lactating, or of child-bearing potential and not using a highly effective contraceptive method.
- Administration of corticosteroids (systemic or nasal) or of anti-histaminic drugs within a defined time period preceding the trial (screening visit), as defined in the section Screening/Baseline Assessments and Procedures; exception made for routine (previously prescribed) control medication for asthmatic participants.
- Laboratory values: a. Missing laboratory values relevant for inclusion, b. Participants with a clinically significant sensitization to other environmental allergens (i.e., house dust mites, cat dander, dog dander) and whose CAP class of the respective allergen specific IgE is higher than for birch pollen specific IgE (t3), c. Clinically relevant laboratory values (haematology, clinical chemistry), grade ≥2 according to the FDA Guidance for Industry for preventive Vaccine Trials (FDA 2007) at screening visit (Participants with laboratory values ≥ grade 2 will require retesting. Upon normalization of the out-of-range value(s), participant will be eligible).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 04 Nov 2024 | 360 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
EMADINE 0.5 mg/ml, eye drops, solution | Other | EYE DROPS, SOLUTION | OPHTHALMIC USE | 0.1 | 4 | PRD9138446 |
AVAMYS 27.5 micrograms/spray, nasal spray suspension | Other | NASAL SPRAY SUSPENSION | NASAL SPRAY | 110 | 4 | PRD2139571 |
Rupatadin AL 10 mg Tabletten | Other | TABLETTEN | OPHTHALMIC USE | 10 | 4 | PRD3786477 |
HAL Allergy Prick Test Hundeepithelien | Other | PRICK TEST | SUBCUTANEOUS | 0.02 | 1 | PRD630687 |
Mometason ratiopharm 50 Mikrogramm/Sprühstoß Nasenspray, Suspension | Other | NASENSPRAY, SUSPENSION | NASAL SPRAY | 200 | 4 | PRD2205394 |
ALLERGOPHARMA
HISTAMIN 1 + 999
zur Positivkontrolle beim Prick-Test
Pricktestlösung zur Anwendung bei Kindern oder
Erwachsenen | Other | PRICKTESTLÖSUNG | SUBCUTANEOUS | 0.02 | 1 | PRD1998980 |
Flutica-Teva® 50 Mikrogramm Nasenspray, Suspension | Other | NASENSPRAY, SUSPENSION | NASAL SPRAY | 160 | 4 | PRD2103953 |
Ebastin Aristo 10 mg Filmtabletten | Other | FILMTABLETTEN | ORAL USE | 20 | 4 | PRD570814 |
Desloratadin Glenmark 5 mg Tabletten | Other | TABLETTEN | ORAL USE | 5 | 4 | PRD442247 |
Placebo will be identical in appearance to the investigational medicinal product. | Placebo | N/A | SUBCUTANEOUS INJECTION | 0 | 19 | N/A |