Evaluation of Efficacy and Safety of Subcutaneous Immunotherapy with Modified Allergen Extracts in Allergic Rhinitis/Rhinoconjunctivitis with or without Asthma
- Trial ID
- 2024-514524-16-00
- Protocol
- DMV02-SIT-026
- Sponsor
- Inmunotek S.L.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **clinical efficacy** of subcutaneously administered polymerized allergen extracts compared to placebo in subjects with **rhinitis/rhinoconjunctivitis** according to the ARIA classification, with or without controlled intermittent or persistent (mild-moderate) asthma, as defined by GEMA 5.0 during pollen season and pollen peak of grasses and cupressaceae. This is clinically relevant as it aims to determine the effectiveness of a potential treatment for patients suffering from these allergic conditions, which can significantly impact quality of life.
Secondary objectives include assessing the safety and efficacy of the polymerized extracts under the specified conditions by comparing the active and placebo groups at both the beginning and the end of the study on all secondary variables. This will provide additional insights into the treatment's overall safety profile and its potential benefits beyond the primary efficacy endpoints.
Participants
The clinical trial involves a study population comprising **both male and female** subjects aged between 12 and 65 years. The participants are individuals with a confirmed clinical history of moderate-severe intermittent or persistent **allergic rhinitis/rhinoconjunctivitis**, with or without controlled mild-moderate intermittent or persistent allergic asthma. The trial does not include a vulnerable population. Participants were selected based on specific criteria, including a positive skin prick test to standardized extracts of grass pollen or cupressaceae, and specific IgE levels greater than 3.5 kU/L. Lifestyle considerations include the requirement for participants to have a smartphone to record symptoms and medication consumption. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
This clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of subcutaneous immunotherapy in patients with **allergic rhinitis/rhinoconjunctivitis** with or without mild to moderate asthma, sensitized to grasses and cupressaceae. The trial involves the administration of a mixture of modified allergen extracts of six grasses and a modified allergen extract of **Juniperus oxycedrus**. The study is expected to last until December 2025, with participant recruitment having commenced in June 2021. The trial is structured to include several key visits: an initial screening visit, multiple follow-up visits, and a final end-of-study visit. The screening visit will determine eligibility based on inclusion criteria such as age, clinical history of inhalation allergy, and specific IgE levels. Follow-up visits will monitor the participants' response to treatment and any adverse events. The end-of-study visit will assess the overall outcomes and safety of the treatment.
Participants are expected to be involved in the study for a maximum treatment period of 12 months. The study will be conducted in accordance with the ARIA and GEMA 5.0 classifications, focusing on the pollen season and peak periods for grasses and cupressaceae. The primary endpoint is the combined symptom and medication score during these periods. Secondary endpoints include symptom-free days, medication-free days, and various symptom and medication scores for both rhinitis/rhinoconjunctivitis and asthma. Participants may be withdrawn from the study early 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 safety and efficacy of the allergen extracts, contributing to the understanding of treatment options for allergic rhinitis/rhinoconjunctivitis and asthma.
Treatment
The clinical trial involves the administration of a **mixture of modified allergen extracts** of six grasses (MG01) and a modified allergen extract of **Juniperus oxycedrus** (T521). This experimental medication is provided in the form of a **suspension for injection**. The active substances include allergenic extracts of Juniperus oxycedrus pollen polymerized with glutaraldehyde, allergen extract from Phleum pratense pollen, Festuca pratensis pollen allergoid, Holcus lanatus pollen allergoid, Poa pratensis pollen polymerized extract, Dactylis glomerata pollen polymerized extract, and Lolium perenne pollen polymerized extract. The pharmaceutical form is a suspension for injection, and the route of administration is subcutaneous. The maximum daily dose is 0.5 ml, with a total treatment period of up to 12 months. The administration schedule is designed to ensure participant compliance, with regular monitoring throughout the trial.
The study also includes a **placebo** group, which receives an identical solution and presentation as the active treatment but without active ingredients. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in the same manner as the active treatment, subcutaneously, and follows the same dosing schedule to ensure consistency across the study groups.
Efficacy
The clinical trial aims to evaluate the efficacy of subcutaneously administered polymerized allergen extracts in patients with rhinitis/rhinoconjunctivitis, with or without mild to moderate asthma, sensitized to grasses and cupressaceae. Efficacy will be assessed using a combination of primary and secondary endpoints. The primary endpoint is the Combined Symptom and Medication Score (RCSMS) for rhinitis/rhinoconjunctivitis during the pollen season and pollen peak of cupressaceae (January, February, and March) and grasses (May and June).
Secondary endpoints include various symptom and medication scores, such as Symptom Free Days, Medication-Free Days, Symptom Score (RSS), Medication Score (RMS), Combined Symptom and Medication Score (ACSMS), Asthma Symptom Score (ASS), Asthma Medication Score (AMS), and Asthma and Rhinitis/Rhinoconjunctivitis Symptom and Medication Scores (ARSS and ARMS). Additional assessments involve the time to first occurrence of asthmatic exacerbations, Visual Analogue Scale (VAS), immunological parameters (total IgE, specific IgE, and specific IgG4), Asthma Control Questionnaire (ACQ-6), and Rhinitis Follow-up Questionnaire (ESPRINT-15). The safety of specific immunotherapy will also be evaluated by monitoring adverse events and reactions at the administration site.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subject who has signed the informed consent form.
- Subjects of both sexes aged between 12 and 65 years.
- Subjects with a confirmed clinical history of inhalation allergy (moderate-severe intermittent or persistent rhinitis and/or rhinoconjunctivitis according to the ARIA classification, with or without mild-moderate controlled intermittent or persistent asthma according to the GEMA 5.0 classification) caused by grass and cupressaceae allergy. The diagnosis of asthma will be valid from 12 months prior to signing the informed consent.
- Subjects with a positive skin prick test (wheal major diameter ≥ 5 mm) to a standardised extract mixture of grass pollen (Phleum pratense, Holcus lanatus, Dactylis glomerata, Poa pratensis, Festuca elatior, Lolium perenne), or to one of the components of the mixture and a cupressaceae extract. In addition, the wheal major diameter must be greater than or equal to that of the histamine.
- Specific IgE (CAP or Immulite) to a grass mixture or to one of the components of the grass mixture, preferably to Phleum pratense and cupressaceae or to one of the molecular components of the allergenic sources with a value > 3.5 KU/L.
- Women of childbearing age (from menarche) must present a urine pregnancy test with negative result at the time of entry into the trial.
- Women of childbearing age participating in the trial must agree to use an appropriate method of contraception. Medically acceptable methods of contraception are intrauterine devices inserted at least 3 months in advance, surgical sterilisation (e.g., tubal ligations), barrier methods, or the use of oral contraceptives.
- Subjects able to comply with the dosing regimen.
- Subjects with a smartphone to record symptoms and medication consumption.
- Subjects with negative skin test for co-seasonal pollens. In case specific IgE determination has been performed, the result must be < 3.5 kU/L and without relevant clinical signs.
- Subjects with negative skin test for other aeroallergens (mites, dander, and fungi). In case specific IgE determination has been performed, the result must be < 3.5 kU/L and without relevant clinical signs.
Exclusion Criteria
- Subjects with positive skin prick test to other aeroallergens, except for dander with occasional exposure and symptomatology.
- Subjects with positive skin prick test for other aeroallergens, except for non-co-seasonal pollens with grasses and cupressaceae.
- Subjects who have received immunotherapy to pollens in the last 5 years or are currently receiving immunotherapy with any allergen.
- Subjects in whom immunotherapy may be subject to absolute general contraindication according to the criteria of the Immunotherapy Committee of the Spanish Society of Allergy and Clinical Immunology and the European Allergy and Clinical Immunology Immunotherapy Subcommittee.
- Subjects with severe or uncontrolled persistent asthma, with an FEV1<70% of baseline despite adequate pharmacological treatment at the time of inclusion in the trial. Also subjects with intermittent or persistent rhinitis/rhinoconjunctivitis with severe symptoms in whom discontinuation of oral or systemic antihistamine treatment is contraindicated.
- Subjects who have previously exhibited a severe secondary reaction during diagnostic skin prick test.
- Subjects on treatment with ß-blockers.
- Clinically unstable subjects at the time of inclusion in the trial (acute asthma exacerbation, respiratory infection, febrile process, acute urticaria, etc.).
- Subjects with chronic active urticaria, severe dermographism, severe atopic dermatitis, sunburn, active psoriasis with lesions in areas where skin prick test will be performed, or a history of hereditary angioedema.
- Subjects with any pathology in which the administration of adrenaline is contraindicated (hyperthyroidism, hypertension, heart disease, etc.).
- Subjects with any other disease not related to moderate rhinoconjunctivitis or asthma, but of potential severity and that may interfere with treatment and follow-up (epilepsy, psychomotor impairment, uncontrolled diabetes, malformations, multiple surgeries, nephropathies).
- Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumour diseases or diagnosed with immunodeficiencies.
- Subject whose condition prevents him/her from offering cooperation and/or who has severe psychiatric disorders.
- Subjects with known allergy to components of the investigational medicinal product other than the allergen.
- Subjects with lower respiratory tract diseases other than asthma such as emphysema or bronchiectasis.
- Subjects who are immediate family members of investigators.
- Pregnant or breastfeeding women.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 10 Jun 2021 | 180 |
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 |
|---|---|---|---|---|---|---|
Identical solution and presentation as the active treatment, but without active ingredients. | Placebo | N/A | — | — | — | N/A |
Mixture of modified allergen extracts of 6 grasses (MG01) and modified allergen extract of Juniperus oxycedrusT521 | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS USE | 0.5 | 12 | PRD11322030 |
Mixture of modified allergen extracts of 6 grasses (MG01) and modified allergen extract of Juniperus oxycedrusT521 | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS USE | 0.5 | 12 | PRD11321906 |