A Randomized, Double-Blind, Placebo-Controlled Study of Subcutaneous Mannan-Conjugated Betula Pendula Pollen Allergoid in Birch Pollen-Induced Allergic Rhinitis
- Trial ID
- 2023-508013-16-00
- Protocol
- T502-SIT-068
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the clinical impact of **T502 treatment** administered subcutaneously to participants with **birch pollen-induced allergic rhinitis** or **rhinoconjunctivitis**. This assessment is crucial for determining the therapeutic efficacy of the mannan-conjugated birch pollen allergoids in alleviating symptoms associated with these allergic conditions. The study is designed as a prospective, randomized, double-blind, placebo-controlled multicentre trial, ensuring robust and reliable results. No secondary objectives have been specified for this trial.
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 a requirement that at least 10% of the participants are adolescents aged 12-17 years in Poland, or aged 18-64 years in Germany. Participants are required to be in good physical and mental health, with confirmed normal renal and liver function. The trial includes individuals with a history of moderate to severe allergic rhinitis or rhinoconjunctivitis for birch pollen allergens for at least two previous seasons, confirmed by a positive skin prick test and specific IgE levels. Female participants of childbearing potential must use a highly effective method of contraception and have a negative pregnancy test at screening. The trial also includes asthmatic participants with a confirmed diagnosis of controlled asthma, as per the Global Initiative for Asthma guidelines. The sponsor has not provided the total number of participants for this trial.
Plans and Procedures
The clinical trial is a **prospective, randomized, double-blind, placebo-controlled** multicentre study designed to evaluate the clinical impact of a **mannan-conjugated allergoid (polymerized) Betula pendula parenteral vaccine** administered subcutaneously to adolescent and adult patients with **birch pollen-induced allergic rhinitis or rhinoconjunctivitis**. The trial aims to assess the efficacy of the investigational treatment by comparing the Combined Symptom and Medication Score (CSMS) over the peak birch pollen season in 2024 between the placebo and active treatment groups. The study is expected to commence recruitment on January 2, 2024, and conclude by May 31, 2024, with a maximum treatment period of 12 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 confirmed diagnosis of birch pollen allergy. The inclusion criteria require participants to be aged between 12 and 64 years, in good physical and mental health, and to have a history of moderate to severe allergic rhinitis or rhinoconjunctivitis for at least two previous seasons. Females of childbearing potential must use a highly effective method of contraception and have a negative pregnancy test at screening. The trial will include follow-up visits to monitor the participants' response to the treatment and any adverse events. The end-of-study visit will evaluate the overall outcomes and gather final data for analysis.
Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The investigational product, administered as a **solution for injection**, will be compared to a placebo that is identical in appearance. The trial is not classified as a low-intervention study and is categorized as a therapeutic confirmatory trial. The study will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.
Treatment
The clinical trial involves the administration of a **Mannan-conjugated allergoid (polymerized) Betula pendula parenteral vaccine**. This investigational medicinal product is formulated as a **solution for injection** and is intended for subcutaneous administration. The active substance in this vaccine is **Betula pendula pollen allergoid, mannan-conjugated, polymerised**, which is classified as a structurally diverse substance and allergen. The vaccine is manufactured by INMUNOTEK S.L. The dosing regimen involves a maximum daily dose of 0.5 ml, with a total maximum dose of 2.3 ml over a treatment period of up to 12 months. The primary objective of the trial is to evaluate the clinical impact of this treatment in participants with birch pollen-induced allergic rhinitis or rhinoconjunctivitis.
The study also includes a **placebo** that is identical in appearance to the investigational medicinal product. The placebo is used as a comparator to assess the efficacy and safety of the experimental vaccine. The placebo is administered in the same manner as the active treatment, ensuring that the study remains double-blind. This design allows for a rigorous evaluation of the vaccine's effects while maintaining participant and investigator blinding.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the clinical impact of the T502 treatment on participants with birch pollen-induced allergic rhinitis or rhinoconjunctivitis. The primary endpoint for efficacy evaluation is the **Combined Symptom and Medication Score (CSMS)**, which will be compared between the placebo and active treatment groups over the peak birch pollen season in 2024. This score is a comprehensive measure that combines both symptom severity and the amount of medication required to manage symptoms, providing a holistic view of the treatment's effectiveness.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated Informed Consent Form a. by a legally competent participant, b. For adolescents: self-completed (signed and dated) participant informed consent to participate in the trial and signed and dated Informed Consent Form by both parents/legal guardian(s)
- Patients aged from 12 to 64 years (at least 10% of the population should be 12-17 years of age (valid for Poland) OR patients aged from 18-64 years (valid for Germany)
- Being in good physical and mental health
- 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 1 will require retesting. Upon normalization of the outof- range value(s), the participant will be eligible)
- Females 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: a. Oral, intravaginal or transdermal hormonal medical drugs or -devices containing oestrogen/progesterone combinations. b. Oral, injectable or implantable hormonal medical drugs or -devices containing progesterone-only. c. Intrauterine device (IUD); d. Intrauterine hormone-releasing system (IUS) e. Bilateral tubal occlusion f. 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) g. Sexual abstinence (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 participant). or 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.)
- Female participants with childbearing potential must have a negative pregnancy test in serum at screening
- 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 for birch pollen allergens for at least 2 previous seasons (definition of allergy severity according to ARIA), b. 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, c. Specific IgE against birch pollen allergens (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 subject has CAP class 3 or higher), d. Being treated with anti-allergic medication for at least 2 seasons prior to enrolment
- For asthmatic participants: confirmed diagnosis of controlled asthma during the treatment period according to Global Initiative for Asthma (GINA) guidelines (steps 1-3, GINA 2022)
- FEV1 ≥80% of the participant’s reference value or Peak Expiratory Flow (PEF) ≥80% of the participants´ individual optimal value (for asthmatic participants only)
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 study period
- Participants with a 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
- Being in any relationship or dependence with the Sponsor, CRO and/or Investigator
- Inability to understand instructions/study documents
- 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 severe systemic reactions and/or anaphylaxis, including to food (e.g., peanut, marine animals) or to Hymenoptera venom (e.g., bee, wasp stings) or to medication (e.g., penicillin), etc.
- Participants who have a suspected or symptoms of a SARS-COV-2 infection, who have had contact with a confirmed case of COVID-19 up to 3 days prior to the screening visit
- 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 2022) 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
- History of a respiratory tract infection and/or exacerbation of asthma within 4 weeks before the screening
- 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 (systemicoral 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 Proceduresnon-allowed drugs and procedures; exception made for routine (previously prescribed) control medication for asthmatic participants
- Clinically relevant laboratory values, i.e., grade ≥2 according to the FDA Guidance for Industry for preventive Vaccine Trials (FDA 2007) at screening visit (Participants with laboratory values > grade 1 will require retesting. Upon normalization of the outof- range value(s), participant will be eligible)
- Participants for who the Investigator believes will not comply with the study 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 02 Jan 2024 | 200 |
 Poland | Not Recruiting | 02 Jan 2024 | 400 |
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 |
|---|---|---|---|---|---|---|
placebo will be identical in appearance to the investigational medicinal product | Placebo | N/A | — | — | — | N/A |
Mannan-conjugated allergoid (polymerized) Betula pendula parenteral vaccine | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 0.5 | 12 | PRD10822626 |