Dose-finding study of polymerized grass pollen extract in patients with allergic rhinoconjunctivitis with or without asthma
- Trial ID
- 2025-520581-22-00
- Protocol
- PRO-RCT-GRAM-2025-01
- Sponsor
- Probelte Pharma S.L.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to establish the optimal therapeutic dose of **Beltavac** with a polymerized extract of grass pollen mixture, administered in a rush regimen, for the treatment of **allergic rhinoconjunctivitis**. This objective is clinically relevant as determining the optimal dose can enhance treatment efficacy and safety for patients suffering from allergic rhinoconjunctivitis, potentially improving their quality of life and reducing symptoms associated with exposure to grass pollen.
Secondary objectives include assessing the effect on specific immunoglobulin serum levels. This evaluation is important for understanding the immunological response to the treatment, which may provide insights into the mechanism of action and long-term benefits of the therapy.
Participants
The clinical trial involves participants diagnosed with **allergic rhinoconjunctivitis** due to exposure to grass pollen. The study population comprises both male and female subjects aged between 18 and 65 years, all of whom are in good physical and mental health. Participants were selected based on their confirmed normal renal and liver function and a history of allergic rhinoconjunctivitis for at least the previous two pollen seasons. The trial does not include a vulnerable population. Participants are required to have a positive skin prick test and specific IgE against grass pollen allergens. Asthmatic participants must have a confirmed diagnosis of controlled asthma according to GINA guidelines. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations include the use of anti-allergic medication for at least the previous pollen season prior to enrollment. Female participants of childbearing potential must adhere to effective contraception methods and have a negative pregnancy test before randomization.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the optimal dose of Beltavac® with a polymerized extract of grass pollen mixture in patients with **allergic rhinoconjunctivitis** associated or not with asthma. The trial aims to establish the optimal therapeutic dose administered in a rush regimen for the treatment of allergic rhinoconjunctivitis. The study will involve a total duration of 24 months, with an estimated recruitment start date of July 1, 2025, and an estimated end date of March 31, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific inclusion criteria, such as age, health status, and confirmed diagnosis of grass pollen allergy. The trial will include multiple follow-up visits to monitor the participants' response to the treatment and to collect data on primary and secondary endpoints. The primary endpoint is the proportion of patients whose reactivity to the Conjunctival Provocation Test (CPT) with grass extract decreases between baseline and visit 7. Secondary endpoints include serum values of total IgE, grass-specific IgE, and IgG4 at baseline and the final visit.
The expected length of participant involvement is up to 24 months, with conditions for early termination including significant adverse events or withdrawal of consent. Participants will receive either the active treatment or a placebo via **subcutaneous injection**. The trial will ensure that all participants are blinded to the treatment allocation to maintain the integrity of the study results. The study will adhere to rigorous ethical standards, including obtaining informed consent and ensuring participant safety throughout the trial duration.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The **experimental medication** is the **BELTAVAC polymerized grass mix**, which is a **suspension for injection**. This medication contains an **allergenic extract of grass pollen mixture** from Dactylis glomerata, Festuca pratensis, Lolium perenne, Phleum pratense, and Poa pratensis in equal parts, polymerized. The pharmaceutical form is a suspension for injection, and it is administered via **subcutaneous injection**. The maximum daily dose is 0.5 ml, with a total maximum dose of 0.5 ml, administered over a maximum treatment period of 24 weeks. The product is not a pediatric formulation and is used as part of an immunotherapy regimen.
The **placebo** used in the study is also a **solution for injection** and is administered via **subcutaneous injection**. The placebo is chemically derived and serves as a control to evaluate the efficacy of the BELTAVAC polymerized grass mix. The placebo does not have an active substance and is used to maintain the double-blind nature of the trial.
Additionally, the study includes the use of **conjunctival provocation and BELTAPRICK-tests** as auxiliary treatments. These tests are categorized under the ATC code V04CL, which pertains to tests for allergic diseases. The administration route for these tests is local use, and they are conducted over a maximum period of 3 weeks. These tests are part of the immunotherapy regimen and are used to assess the allergic response in participants.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The trial is designed to establish the optimal therapeutic dose of the BELTAVAC polymerized grass mix for the treatment of **allergic rhinoconjunctivitis**, with or without associated asthma.
Efficacy
Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of patients whose reactivity to the **Conjunctival Provocation Test (CPT)** with grass extract decreases between baseline and visit 7. This is defined as the titrated 10-fold step allergen concentration required to develop a positive response being at least one dose higher. This endpoint will be measured at baseline and at visit 7 to determine changes in allergen reactivity.
Secondary endpoints include the serum values of total IgE, grass-specific IgE, and IgG4 at baseline and the final visit. Additionally, serum Phl p1 and Phl p5 specific IgE and IgG4 values will be measured at baseline and the final visit (V0 and V7). These biomarkers will be collected and analyzed to evaluate the immunological response to the treatment. The schedule for these measurements is set at the beginning and end of the treatment period to assess changes over time.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated Informed Consent Form a. by a legally competent participant,
- Patients (males or females) aged from 18 to 65 years
- 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. Upon normalization of the out-of-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 sterilization 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 estrogen/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. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository It should always be supplemented with the use of a spermicide. h. 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 visit 1 (before randomization),
- Having the diagnosis of grass pollen allergy based on all the following criteria: a. A medical history of allergic rhinoconjunctivitis for grass pollen allergens for at least the previous two pollen seasons, b. A medical history of moderate to severe rhinitis for grass pollen allergens for at least the previous two pollen seasons (definition of allergy severity according to ARIA, see Figure 2, c. A positive skin prick test (Beltaprick Test®, SPT - wheal diameter ≥3 mm) to grass pollen allergens, positive control (histamine) wheal ≥3 mm, negative control (NaCl) wheal <2 mm, d. Specific IgE against grass pollen allergens in serum (minimum CAP class 3 or higher, ≥3.5 kU/L), e. Phl p1 and/or Phl p5 specific IgE in serum ≥ 3,5 kU/l, f. A positive CPT at the visit 1, meaning a Total Symptom Score (TSS) ≥ 5 (adjusted with respect to the reference eye), g. Being treated with anti-allergic medication for at least the previous pollen season 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 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).
Exclusion Criteria
- Simultaneous participation in other clinical trials or previous participation within 30 days before inclusion,
- Previous immunotherapy with grass pollen allergens within the last 5 years,
- Ongoing immunotherapy with grass pollen allergens or any other allergens,
- Participants with acute allergic rhinitis/rhinoconjunctivitis due to other environmental allergens during the CPT performance,
- Participants with a sensitization to other environmental allergens (i.e., other pollens, house dust mites, cat dander, dog dander or other perennial antigens) when they present relevant symptoms that can interferes the CPT performance,
- Being in any relationship or dependence with the Sponsor, CRO and/or Investigator
- Inability to understand instructions/study documents,
- History of severe systemic reactions and/or anaphylaxis, including 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, (26))
- 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 2 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,
- 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 before the screening visit (V0), as defined in the Table 6: Waiting period for screening; 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. Upon normalization of the out-of-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.
- Ocular disorders, such as inflammation/infection of the conjunctiva, cornea, or iris and in case of severe dry eye syndrome.
- Any type of eye surgery in the last 6 months.
- Ocular surface diseases in which IgE-mediated hypersensitivity is not involved: Sjögren’s syndrome, blepharitis, blepharoconjunctivitis, urban ocular allergy syndrome, dry eye syndrome, giant papillary conjunctivitis after intolerance to contact lenses or foreign bodies.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Not Yet Recruiting | 01 Jul 2025 | 40 |
 Spain | Not Yet Recruiting | 01 Jul 2025 | 80 |
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 | Placebo | — | SUBCUTANEOUS INJECTION | 0 | 24 | SUB21402 |
BELTAVAC polymerized grass mix | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS INJECTION | 0.5 | 24 | PRD11165325 |
BELTAVAC polymerized grass mix | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS INJECTION | 0.5 | 24 | PRD11165324 |
BELTAVAC polymerized grass mix | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS INJECTION | 0.5 | 24 | PRD12012794 |
- | Other | PHF00024MIG | LOCAL USE | 5 | 3 | V04CL |