Efficacy and Safety Evaluation of PQ Birch in Patients with Birch Pollen-Induced Seasonal Allergic Rhinitis and Rhinoconjunctivitis
- Trial ID
- 2023-507427-28-00
- Protocol
- PQBirch302
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **efficacy** of PQ Birch 27300 SU in subjects with birch pollen-induced **seasonal allergic rhinitis** and/or **rhinoconjunctivitis**. This is clinically relevant as it aims to determine the therapeutic potential of PQ Birch in alleviating symptoms associated with these conditions, which can significantly impact patients' quality of life during the birch pollen season.
Secondary objectives include:
- Evaluating the efficacy of PQ Birch on the combined symptom and medication score (CSMS) over the entire birch pollen season (BPS).
- Assessing the efficacy on the daily symptom score (dSS) and daily medication score (dMS) components of the CSMS during the peak BPS.
- Evaluating the efficacy on the total combined score (TCS) during the peak BPS.
- Assessing the efficacy on the CSMS during the peak tree pollen season (TPS).
- Evaluating the disease-specific burden on quality of life.
- Assessing the effect of PQ Birch on **IgG4** levels.
- Evaluating the safety and tolerability of PQ Birch in subjects with birch pollen-induced seasonal allergic rhinitis and/or rhinoconjunctivitis.
Participants
The clinical trial focuses on evaluating the efficacy of PQ Birch 27300 SU in individuals with **seasonal allergic rhinitis** and/or rhinoconjunctivitis induced by birch pollen. The study population comprises both male and female participants aged between 18 to 65 years. Participants are required to be in good general health, as assessed by the investigator through medical evaluations, including medical history, physical examination, and laboratory tests. The trial includes individuals with a documented history of moderate to severe symptoms of seasonal allergic rhinitis or rhinoconjunctivitis due to birch pollen exposure for at least two seasons, despite previous allergy pharmacotherapy. Participants must have a positive skin prick test (SPT) for birch pollen and histamine, and a negative SPT to the negative control. 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 **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of Pollinex Quattro Plus 1.0 mL Birch in subjects with **seasonal allergic rhinitis and/or rhinoconjunctivitis** induced by birch pollen exposure. The trial will involve a series of study visits, beginning with an inclusion (screening) visit, followed by multiple follow-up visits, and concluding with an end-of-study visit. The estimated duration of the trial is from March 2025 to October 2026, with participant involvement expected to last up to 18 months.
Participants will be randomly assigned to receive either the active treatment or a placebo, which consists of 2% (w/v) L-tyrosine and 0.5% (w/v) phenol for subcutaneous use. The trial will include a screening visit to assess eligibility based on criteria such as age, health status, and specific **IgE** levels. Follow-up visits will be conducted to monitor the efficacy and safety of the treatment, with primary endpoints focusing on the Combined Symptom and Medication Score (CSMS) averaged over the peak birch pollen season. Secondary endpoints will include additional efficacy measures and safety assessments, such as the frequency and severity of adverse events.
The trial will conclude with an end-of-study visit to evaluate the overall outcomes and any long-term effects of the treatment. Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The trial aims to provide comprehensive data on the treatment's impact on **seasonal allergic rhinitis and/or rhinoconjunctivitis**, contributing to the understanding of its potential benefits and risks.
Treatment
The clinical trial involves the administration of **Pollinex Quattro Plus 1.0 mL Birch**, a **suspension for injection**. This experimental medication is designed to evaluate its efficacy and safety in subjects with seasonal allergic rhinitis and/or rhinoconjunctivitis induced by birch pollen exposure. The active substance in this formulation is a placebo, categorized under the ATC code V01AA05, which corresponds to tree pollen. The medication is administered via **subcutaneous injection**. The maximum daily dose is 6000 SU, with a total maximum dose of 27300 SU over a treatment period of 18 weeks. The product is manufactured by Allergy Therapeutics (UK) Ltd and is not a pediatric formulation.
The trial also includes a **placebo** control, which consists of a solution containing 2% (w/v) L-tyrosine and 0.5% (w/v) phenol, intended for subcutaneous use. This placebo is used to maintain the double-blind nature of the study, ensuring that neither the participants nor the investigators know which treatment is being administered. The placebo is administered in the same manner as the experimental medication, via subcutaneous injection, to ensure consistency in the administration process. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.
Efficacy
The efficacy of the investigational product, Pollinex Quattro Plus 1.0 mL Birch, will be assessed in a randomized, double-blind, placebo-controlled clinical trial involving subjects with seasonal allergic rhinitis and/or rhinoconjunctivitis induced by birch pollen exposure. The primary endpoint for evaluating efficacy is the Combined Symptom and Medication Score (CSMS) averaged over the peak birch pollen season (BPS). Secondary efficacy endpoints include the CSMS averaged over the entire BPS, the daily Symptom Score (dSS) component of the CSMS averaged over the peak BPS, the daily Medication Score (dMS) component of the CSMS averaged over the peak BPS, and the Total Combined Score (TCS) averaged over the peak BPS. Additionally, the CSMS will be averaged over the combined peak seasons for alder, hazel, birch, and oak pollen season (peak TPS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)) will be measured at Visit 11. Serum birch-specific IgG4 levels will be compared at pre-BPS (Visit 9) to baseline levels.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Capable of giving signed informed consent as described in Appendix 1 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this clinical trial protocol and to attend required clinical trial visits.
- Subject who has a signed and dated ICF.
- Subject must be 18 to 65 years of age inclusive, at the time of signing the ICF.
- Male or female.
- For female subjects only: Female subjects who are not of childbearing potential (defined as at least 12 months natural spontaneous amenorrhoea, or at least 6 weeks following surgical menopause/permanent sterilisation [hysterectomy, bilateral oophorectomy and bilateral salpingectomy]) or females of childbearing potential who agree to comply with the contraceptive requirements of the clinical trial protocol.
- Good general health, as determined by the Investigator, based on a medical evaluation, including medical history, physical examination, mental status assessment and laboratory tests. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the clinical trial procedures.
- Positive history of moderate to severe symptoms of SAR/rhinoconjunctivitis ascribed to birch pollen exposure of at least 2 seasons’ duration, despite having received allergy pharmacotherapy (e.g., antihistamines, nasal corticosteroids, leukotriene modifiers, etc.) during the last 2 consecutive birch pollen seasons prior to the clinical trial, confirmed by subject records.
- A positive SPT to histamine (wheals [longest diameter] ≥3 mm) and a negative SPT to the negative control (wheal diameter = 0 mm) at screening.
- A positive SPT for birch pollen (wheals [longest diameter] ≥3 mm).
- Birch-specific IgE class ≥2 (i.e., ≥0.71 kUA/L) as documented by an ImmunoCAP test at screening.
- Forced expiratory volume in one second (FEV1) ≥70% of predicted and PEFR ≥70% of predicted at screening.
Exclusion Criteria
- Pregnant or lactating subject.
- Presence of any medical history of moderate to severe allergy symptoms.
- Moderate to severe symptoms during the 3 years prior to Visit 1 to any other seasonal or perennial allergen not tested in the sIgE measurements done at screening that cannot be avoided during Period 1 to Period 3 of the clinical trial and the symptoms of which may interfere with administration of treatment and/or impact the data collected.
- Presence of any medical condition that may reduce the ability to survive a serious allergic reaction.
- Presence of active systemic autoimmune disorder, systemic autoimmune disorders in remission or active organ specific autoimmune disorder.
- Presence of active malignant neoplasia, severe cardiovascular disease (e.g., coronary artery disease, cardiac insufficiency, etc.), pulmonary insufficiency, severe psychiatric disorders or primary and secondary immunodeficiencies.
- History of any other immunological disorder or other diseases (including, but not limited to cardiovascular [including uncontrolled or inadequately controlled hypertension], gastro-intestinal, hepatic, renal, haematological, neurological, endocrine or pulmonary disease) that in the opinion of the Investigator may pose a safety risk or compromise the interpretation of efficacy of the clinical trial treatment.
- Presence of severe or poorly controlled or uncontrolled asthma as defined in the protocol.
- Presence of non-atopic rhinitis.
- Presence of chronic rhino-sinusitis. Chronic rhino-sinusitis will be diagnosed when at least two of the following four symptoms are present and occur for more than 12 weeks: (1) purulent drainage, (2) facial and/or dental pain, (3) nasal obstruction, (4) hyposmia.
- Presence of nasal polyps.
- Eye surgery within the past 6 months.
- Presence of any skin conditions (e.g., skin abnormalities, tattoos etc.), which might interfere with the interpretation of the SPT results.
- Clinical history of Type I diabetes or poorly controlled Type II diabetes.
- Moderate to severe upper or lower respiratory infections requiring medication within 14 days before Visit 1.
- Presence of acute or chronic infection, fever or inflammation at Visit 1 or Visit 1a.
- Clinical history of serious systemic reaction in response to AIT in the past.
- Clinical history of life-threatening anaphylactic reactions to foods, insect venom, exercise, drugs or idiopathic anaphylaxis.
- Clinical history of allergy, hypersensitivity or intolerance to the excipients of the investigational drug/placebo.
- Clinical history of allergy, hypersensitivity or intolerance to the relief medications (for relief of allergy symptoms during Period 3) provided for use in this clinical trial.
- Clinical history of hereditary angioedema.
- Clinical history of mast cell disorder including mastocytosis, chronic urticaria or urticaria pigmentosa.
- Unable to receive epinephrine therapy (i.e., use of epinephrine is contraindicated such as in subjects with hyperthyroidism, uncontrolled hypertension, cardiac arrhythmias, closed angle glaucoma or subjects taking other sympathomimetics).
- Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.
- Clinical history of drug or alcohol abuse, which, in the Investigator’s opinion, could interfere with the subject’s ability to participate in the clinical trial.
- Any history of AIT of any type for birch or tree pollen allergy in the past (irrespective of how long ago this was).
- Any history of AIT of any type for any other type of allergy in the past 5 years. Exception: Subjects who received AIT in the past 5 years for food allergy are not excluded.
- Inability to adhere to the washout periods listed in Table 8 of the protocol, with respect to screening and to refrain from using the medications indicated until after Visit 12.
- Treatment with a preparation containing MPL (e.g., Cervarix, Shingrix, Fendrix) within 2 years prior to Visit 1 and until after completion of Visit 12 (with the exception of the investigational drug).
- Previous history of epinephrine auto-injector use.
- β-blocker medication (local or systemic, including eye drops) for any indication.
- Monoamine oxidase inhibitors and tricyclic antidepressants.
- Any previous therapy (within the previous 5 years) or current therapy with biologics such as e.g., anti-IgE (e.g., omalizumab [Xolair]) or anti-interleukins (e.g., mepolizumab).
- Current or past therapy (within the previous 5 years) with any other immunomodulatory therapies.
- Unable to refrain from any vaccination (including influenza vaccine) during the clinical trial (unless administered >30 days prior to randomisation).
- Participation in a clinical research trial with any investigational drug within 4 weeks of Visit 1 or concomitantly with this clinical trial.
- Personal, financial or other dependent relationship (e.g., employee or immediate relative) with the clinical trial site, Sponsor, Sponsor’s representative, or another individual who has access to the clinical trial protocol.
- Vulnerable subjects or those in judicial or governmental detention, detainment or imprisonment in a public institution.
- Subjects likely to have prolonged periods of absence from home to an area with dissimilar pollen burden during the BPS (e.g., business or private travel) of greater than 3 consecutive days in one week (Monday to Sunday) or a total of 7 days during BPS.
- Have changed residence to an area with dissimilar pollen burden (s) since the last BPS.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Yet Recruiting | 01 Mar 2025 | 34 |
 Germany | Not Yet Recruiting | 01 Mar 2025 | 295 |
 Poland | Not Yet Recruiting | 01 Mar 2025 | 233 |
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: 2% (w/v) L-tyrosine and 0.5% (w/v) phenol for subcutaneous use | Placebo | N/A | — | — | — | N/A |
Pollinex Quattro Plus 1.0 mL Birch | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS INJECTION | 6000 | 18 | PRD2563767 |