Efficacy and Safety Evaluation of PQ Grass 27600 SU in Pediatric Patients with Grass Pollen-Induced Seasonal Allergic Rhinitis/Rhinoconjunctivitis
- Trial ID
- 2023-508520-36-00
- Protocol
- PQGrass308
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **efficacy** of PQ Grass 27600 SU in paediatric subjects with seasonal allergic rhinitis/rhinoconjunctivitis induced by grass pollen exposure. This evaluation is crucial for determining the therapeutic potential of PQ Grass in managing symptoms associated with grass pollen allergies in children and adolescents, which can significantly impact their quality of life and daily functioning.
Secondary objectives include:
- Part A Efficacy: Assessing the efficacy of PQ Grass on the Combined Symptom and Medication Score (CSMS) over the entire grass pollen season (GPS), and specifically on the daily symptom score (dSS) and daily medication score (dMS) components during the peak GPS. Evaluating the total combined score (TCS) during the peak GPS, the number of well and severe days, grass-specific IgG4 levels, and quality of life.
- Part A Safety: Evaluating the safety and tolerability of PQ Grass in paediatric subjects with grass pollen-induced seasonal allergic rhinitis (SAR).
- Part B Efficacy: Key secondary objectives include evaluating the long-term efficacy of PQ Grass and IgG4 levels after 3 years of treatment. Other secondary objectives involve assessing the yearly efficacy during the GPS, efficacy on dSS and dMS components during the peak GPS, well and severe days during the GPS, grass-specific IgG4 levels after 1 and 2 years of treatment, quality of life, and asthma control.
- Part B Safety: Evaluating the long-term safety and tolerability of PQ Grass in paediatric subjects with grass pollen-induced SAR.
Participants
The clinical trial involves a total of **50 participants** diagnosed with **seasonal allergic rhinitis** induced by grass pollen exposure. The study population consists of both male and female subjects aged between 4 to 16 years. Participants are required to be in good general health, as assessed by a medical evaluation, and must have a history of moderate to severe symptoms despite previous allergy treatments. The selection criteria include a positive skin prick test to grass pollen and specific IgE levels, ensuring the presence of grass pollen sensitivity. The trial includes children who can perform spirometry or peak flow measurements, and it considers lifestyle factors such as the ability to adhere to the dosing and visit schedule. The trial population was selected based on these criteria to ensure the safety and efficacy of the investigational product in a pediatric population. The study does not specify any particular lifestyle considerations such as diet or physical activity beyond the ability to comply with the trial requirements.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of PQ Grass 27600 SU in children and adolescents with **seasonal allergic rhinitis/rhinoconjunctivitis** induced by grass pollen exposure. The trial is divided into two parts: Part A focuses on the efficacy of PQ Grass 27600 SU during the first year, while Part B assesses the sustained long-term efficacy over a treatment-free follow-up period. The trial is expected to commence recruitment on June 28, 2024, and conclude by October 31, 2032, with an overall duration of approximately eight years.
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 specific **IgE** levels. Following successful screening, participants will be randomized to receive either the active treatment or placebo. The trial includes multiple follow-up visits to monitor efficacy and safety, with assessments of clinical symptoms, quality of life, and laboratory parameters. The end-of-study visit will evaluate the long-term outcomes and any adverse events experienced during the trial.
The expected length of participant involvement is up to three years of treatment, followed by a two-year treatment-free follow-up period. Conditions that may lead to early termination from the study include the occurrence of severe adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial aims to provide comprehensive data on the clinical benefits and safety profile of PQ Grass 27600 SU, contributing to the understanding of its role in managing seasonal allergic rhinitis/rhinoconjunctivitis in the pediatric population.
Treatment
The clinical trial involves the administration of **Pollinex Quattro Grass 1.0 ml**, a **suspension for injection** containing **grass pollen allergen extract modified with glutaraldehyde and adsorbed to L-tyrosine**. This biological product is administered via **subcutaneous injection**. The maximum daily dose is 6000 SU, with a total dose of 27600 SU over a treatment period of 36 weeks. This experimental medication is designed to evaluate its efficacy and safety in children and adolescents with seasonal allergic rhinitis/rhinoconjunctivitis induced by grass pollen exposure.
As a comparator, a **placebo with MCT**, formulated as a **suspension for injection**, is used. This placebo is administered subcutaneously, mirroring the route of administration for the experimental treatment. The placebo serves to maintain the double-blind nature of the trial, ensuring unbiased assessment of the experimental treatment's efficacy.
**Mometasone furoate monohydrate** is included as an auxiliary treatment in the form of a **nasal spray, suspension**. It is administered via **intranasal use** with a maximum daily dose of 200 µg and a total dose of 18000 µg over a 3-week period. This corticosteroid is used to manage symptoms of allergic rhinitis.
**Loratadine** is provided in two formulations: **tablet** and **oral solution**. Both are administered orally with a maximum daily dose of 10 mg and a total dose of 900 mg over a 3-week period. Loratadine is an antihistamine used to relieve allergy symptoms.
**Desloratadine** is available as a **film-coated tablet** and **oral solution**, administered orally with a maximum daily dose of 5 mg and a total dose of 450 mg over a 3-week period. This antihistamine is used to alleviate allergy symptoms.
**Prednisolone** is included in the trial as a **tablet** and **soluble tablet**, administered orally with a maximum daily dose of 40 mg and a total dose of 200 mg over a 5-day period. Prednisolone is a corticosteroid used to reduce inflammation and manage severe allergic reactions.
**Olopatadine hydrochloride** is provided as **eye drops, solution**, administered as eye/ear/nose drops with a maximum daily dose of 2 mg and a total dose of 240 mg over a 4-week period. This antihistamine is used to treat symptoms of allergic conjunctivitis.
**Histamin-Kontrollösung 1% Pricktestlösung** and **Bencard Prick-Testlösung Negativ-Kontrolle** are used as control solutions in **skin-prick tests**. Both are administered via **intraepidermal use**. The histamine solution contains **histamine dihydrochloride** and is used to confirm the skin's reactivity, while the negative control solution contains **phenol** to ensure the absence of a reaction.
**Prick-Testlösung B2 Gräserpollen 10.000 DU/ml ODC** is another solution for **skin-prick tests**, containing a **12 grass pollen mixture**. It is administered via **intraepidermal use** to assess allergic reactions to grass pollen.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include the Combined Symptom and Medication Score (CSMS) averaged over the peak Grass Pollen Season (GPS) during Year 1 for Part A, and the CSMS averaged over the peak GPS after 2 years of treatment-free follow-up for Part B. Secondary endpoints for Part A include the CSMS averaged over the entire or truncated GPS, the daily Symptom Score (dSS) and daily Medication Score (dMS) components of the CSMS averaged over the peak GPS, the Total Combined Score (TCS) averaged over the peak GPS, and the probability of well days and severe days during the peak GPS. Additionally, serum grass-specific IgG4 levels will be measured at Visit 8 and Visit 11 compared to baseline, and quality of life will be assessed using PRQLQ, AdolRQLQ, and RQLQ within the GPS at selected sites at Visit 11 compared to baseline.
For Part B, key secondary endpoints include the CSMS and TCS averaged over the peak GPS after 3 years of treatment, and after 2 years of treatment-free follow-up. Other secondary endpoints involve the CSMS averaged over the peak GPS after 1 and 2 years of treatment and 1 year of treatment-free follow-up, as well as the dSS and dMS components of the CSMS averaged over the peak GPS after 1, 2, and 3 years of treatment and 1 and 2 years of treatment-free follow-up. Serum grass-specific IgG4 levels will also be assessed after 1 and 2 years of treatment compared to baseline. Changes in quality of life will be measured using RQLQ, PRQLQ, and AdolRQLQ within the GPS at selected sites, after 1, 2, and 3 years of treatment, and 1 and 2 years of treatment-free follow-up compared to baseline.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent from a legal representative on the subject’s behalf (with/without assent depending on applicable country-specific regulations).
- Subjects aged 4 to 16 years inclusive at the time of signing the consent (assent) form. The subject must be ≥5 to ≤16 years old at the first randomisation visit.
- Male or female.
- Female subjects are allowed to participate in the trial if: i. Not of childbearing potential (defined as premenarche). ii. Of childbearing potential with a negative urine pregnancy test at all visits and, if sexually active, agree to use 1 highly effective method of contraception, during the whole duration of the trial, starting at least 7 days before first dose administration and for at least 30 days after the last dose of IMP/placebo or after next menstruation, whichever is longer.
- Good general health, as determined by the Investigator based on a medical evaluation including medical history, physical examination 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 trial procedures.
- Positive history of moderate to severe SAR ascribed to grass (Pooideae) pollen exposure, of at least one year duration or by the 5th birthday (for children of 5-6 years old), with moderate to severe SAR symptoms despite having received allergy pharmacotherapy.
- A positive skin prick test (SPT) to grass pollen (wheals [longest diameter] ≥ 3 mm and histamine ≥ 3 mm) and a negative SPT to the negative control (wheal diameter = 0 mm) at screening.
- Grass specific IgE class ≥2 as documented by an immunoCAP test at screening. (Please note: Class ≥2 by an ImmunoCAP test implies grass specific IgE ≥0.71 kUA/L)
- Children who are able to perform spirometry or peak flow measurements.
- Forced expiratory volume in 1 second (FEV1) ≥80% of predicted and FEV1/forced vital capacity (FVC) ≥75% or, if adequate spirometry cannot be performed, PEFR ≥75% predicted at screening and randomisation visit.
- Be able to adhere to dose and visit schedule
Exclusion Criteria
- Pregnant or lactating subject.
- Presence of any medical history of moderate to severe allergy symptoms, to any other seasonal allergen (other than grass) or perennial allergens, confirmed by a positive specific IgE [Class ≥2] at screening.
- Moderate to severe symptoms during the 2 years prior to screening to a perennial or seasonal allergen not tested by IgE (for Exclusion Criterion #2), that cannot be avoided during the trial and the symptoms of which may interfere with administration of treatment and/or impact the data collected, as determined by the Investigator.
- Presence of any medical condition that may reduce the ability to survive a serious allergic reaction.
- History of any autoimmune disease or other immunological disorder or other diseases (including, but not limited to malignancy, cardiovascular, gastro-intestinal, hepatic, renal, haematological, neurological, psychiatric, endocrine or pulmonary disease) that in the opinion of the Investigator may pose a safety risk or compromise the interpretation of efficacy of the trial treatment.
- Presence of severe or poorly controlled asthma as defined by current Global Initiative for Asthma (GINA) guidelines (current GINA) or requiring more than a daily dose above 800 μg (in adolescents) or 400 μg (in children) of inhaled budesonide [or equivalent inhaled corticosteroid].
- Hospital admission for exacerbation of asthma in the 12 months prior to Visit 1 or any history of a life-threatening asthma attack.
- Presence of non-atopic rhinitis and/or rhino-sinusitis (with or without polyps).
- Presence of nasal polyps and/or chronic sinusitis.
- Presence of any acute or chronic ocular disorder, other than allergic conjunctivitis.
- Presence of any skin conditions (e.g., skin abnormalities, tattoos etc.), which might interfere with the interpretation of the SPT results.
- Severe eczema with involvement of more than 25% of the body surface.
- Clinical history of Type I diabetes. Subjects with well-controlled Type II diabetes will be allowed to participate at the discretion of the Investigator.
- Any acute infection (including upper respiratory tract infections in the 7 days prior to Visit 2, which in the opinion of the investigator may pose a safety risk to the subject.
- Clinical history of severe or 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 trial medication.
- Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.
- History of any previous allergen immunotherapy, by any route.
- Unable to meet medication washout requirements listed in the table prohibited medications.
- Unable to receive epinephrine therapy or at greater risk of developing adverse reactions after epinephrine administration as assessed by the Investigator.
- Monoamine oxidase inhibitor medication and tricyclic antidepressants.
- Β-blocker medication for any indication.
- Any previous therapy (within the previous 5 years) or current therapy with anti-IgE (e.g., Xolair), anti-interleukins (ILs) (e.g., mepolizumab) or any other therapy with a biologic agent.
- All vaccinations (including influenza and coronavirus disease 2019 [COVID-19] vaccines, and treatment with a preparation containing MPL [e.g., Cervarix, Fendrix]) administered 30 days or less prior to randomisation or any planned vaccinations during the treatment periods. Influenza and other vaccinations should also be avoided for 30 days after the last injection of every treatment period. Emergency vaccinations (e.g., tetanus due to injury) can be administered at any time.
- Participation in a clinical trial research trial with any IMP within 4 weeks from screening.
- Known fear of injections that in the opinion of the Investigator, may impact adherence to the dosing schedule and cooperation with required clinical trial procedures.
- Clinical history of drug or alcohol abuse which, in the Investigator’s opinion, could interfere with the subject’s ability to participate in the trial.
- Personal, financial or other dependent relationship (e.g., employee or immediate relative) with the 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, except children in long-term foster care, at the discretion of the Investigator.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 28 Jun 2024 | 36 |
 Czechia | Recruiting | 28 Jun 2024 | 32 |
 Germany | Recruiting | 28 Jun 2024 | 92 |
 Lithuania | Recruiting | 28 Jun 2024 | 25 |
 Poland | Recruiting | 28 Jun 2024 | 96 |
 Romania | Recruiting | 28 Jun 2024 | 25 |
 Slovakia | Recruiting | 28 Jun 2024 | 52 |
Sites & Investigators
Research 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 |
|---|---|---|---|---|---|---|
DESLORATADINE | Other | — | ORAL USE | 5 | 3 | SUB01596MIG |
Pollinex Quattro Grass 1.0 ml | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS INJECTION | 6000 | 36 | PRD4868274 |
Prick-Testlösung B2 Gräserpollen 10.000 DU/ml ODC | Other | PRICK-TESTLÖSUNG | INTRAEPIDERMAL USE | 200 | 1 | PRD409398 |
LORATADINE | Other | — | ORAL USE | 10 | 3 | SUB08581MIG |
Placebo with MCT, suspension for injection, subcutaneous use | Placebo | N/A | — | — | — | N/A |
PREDNISOLONE | Other | — | ORAL USE | 40 | 5 | SUB10018MIG |
DESLORATADINE | Other | — | ORAL USE | 5 | 3 | SUB01596MIG |
PREDNISONE | Other | — | ORAL USE | 40 | 5 | SUB10020MIG |
Bencard Prick-Testlösung Negativ-Kontrolle | Other | PRICK-TESTLÖSUNG | INTRAEPIDERMAL USE | 0 | 1 | PRD7747822 |
Histamin-Kontrollösung 1% Pricktestlösung Wirkstoff: Histamindihydrochlorid | Other | PRICKTESTLÖSUNG | INTRAEPIDERMAL USE | 200 | 1 | PRD415035 |