Efficacy and Safety Evaluation of the Treatment of Allergy Against Cupressaceae and Grasses.

Phase 3

Recruiting

• Conditions: Rhinitis, Allergic; Asthma, Allergic; Rhinoconjunctivitis
• Interventions: Other: Placebo subcutaneous; Biological: 10,000 MG01 +10,000 T521; Biological: 30,000 MG01 +10,000 T521

• Registration Number: NCT04898283
• Lead Sponsor: Inmunotek S.L.

Brief Summary

A Randomized, Double-Blinded, Placebo-Controlled, Prospective, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Immunotherapy in Patients With Rhinitis/Rhinoconjunctivitis With or Without Mild to Moderate Asthma Sensitized to cupressaceae and grasses.

Detailed Description

The multicenter study includes 180 subjects sensitised to cupressaceae and grass pollen, both male and female aged 12 to 65 years.

The double-blinded and placebo controlled treatment will last 18 months for each subject.

The primary endpoint of the trial will be the combined rhinitis/rhinoconjunctivitis symptom and medication score (RCSMS) which will be assessed using data collected in the Subject electronic Diary during the cupressaceae (January, February and March) and grass (May and June) pollen seasons.

Study Timeline

• Study First Submitted: 2021-01-04
• Study First Submitted QC: 2021-05-21
• Study First Posted: 2021-05-24
• Study Start: 2021-05-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-13
• Primary Completion: 2026-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Written informed consent.
2. Aged between 12 and 65, both genders
3. Positive suggestive clinical history of intermittent or persistent moderate to severe rhinitis /rhinoconjunctivitis according to ARIA classification, with or without moderate intermittent or persistent asthma,according to GEMA 5.0, due to grass and cupressaceae pollen.
4. Subjects with a positive skin prick-test (wheal size >5 mm diameter) to a standardized mixed extract of grass pollen (Phleum pratense, Holcus lanatus, Dactylis glomerata, Poa pratensis, Festuca elatior, Lolium perenne) or to one of the molecular components of the mixture and to a cupressaceae extract. In addition, the largest diameter of the papules must be greater than or equal to that of the histamine.
5. Specific IgE > 3,5 KU/L , against grass (preferably Phleum pratense) and cupressaceae pollen (InmunoCAP® o Immulite).
6. Women of childbearing age (from menarche) must present a urine pregnancy test with a negative result at the time of joining the trial.
7. Women of childbearing potential participating in the trial, should commit to using an appropriate method of contraception. Medically acceptable methods of contraception are intrauterine devices placed at least 3 months in advance, surgical sterilization (for example, tubal ligation), barrier methods, or the use of oral contraceptives.
8. Subjects capable of complying with the dosing regimen.
9. Subjects who own a smartphone for symptom registration and medication.
10. Subjects with a negative prick test to coestational pollens. In the case specific IgE is available, the result should be <3,5 kU/L and without relevant symptomatology
11. Subjects with a negative prick test to other aeroallergens (dust mites, epitheliums and fungus). In the case specific IgE is available, the result should be <3,5 kU/L and without relevant symptomatology.

Exclusion Criteria

1. Subjects with positive prick test to other aeroallergens except for sensitisation to epithelia with occasional exposure and symptoms.
2. Subjects with positive prick test to other aeroallergens except for sensitisation to pollen noncoseasonal with cupressus or grasses.
3. Subjects who have received prior immunotherapy in the preceding 5 years for any of the allergens tested or a cross-reactive allergen or are currently receiving immunotherapy with any allergen.
4. Subjects in which immunotherapy may be subject to an 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.
5. Subjects with severe or uncontrolled intermittent or persistent asthma, with an FEV1 <70% with respect to the reference value despite adequate pharmacological treatment at the time of inclusion in the trial. Likewise, subjects with intermittent or persistent rhinitis / rhinoconjunctivitis with severe symptoms in which the suspension of oral or systemic antihistamine treatment is contraindicated.
6. Subjects who have previously had a severe secondary reaction during the prick test diagnostic skin test.
7. Subjects treated with beta-blockers.
8. Clinically unstable subjects at the time of inclusion in the trial (acute asthmatic exacerbation, respiratory infection, febrile process, acute urticaria, etc.).
9. Subjects with active chronic urticaria, severe dermographism, severe atopic dermatitis, sunburn, active psoriasis with lesions in areas where skin tests will be performed, or a history of hereditary angioedema.
10. Subjects who have any pathology in which adrenaline administration is contraindicated (hyperthyroidism, HTN, heart disease, etc.).
11. Subjects with any other disease not related to moderate rhinoconjunctivitis or asthma, but potentially serious and that may interfere with treatment and follow-up (epilepsy, psychomotor disorder, uncontrolled diabetes, malformations, multioperated patients, kidney disease,).
12. Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumor diseases or with a diagnosis of immunodeficiencies.
13. Subject whose condition prevents from offering cooperation and/ or who has severe psychiatric disorders.
14. Subjects with a known allergy to components of the investigational medicinal product other than the allergen.
15. Subjects with lower respiratory diseases other than asthma such as emphysema or bronchiectasis.
16. Subjects who are direct relatives of the researchers.
17. Pregnant or lactating women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo subcutaneous	Placebo subcutaneous	The same solution and presentation as the active treatment, but without active ingredients.
10,000 MG01 + 10,000 T521	10,000 MG01 +10,000 T521	10,000 TU/mL of MG01 + 10,000 TU/mL of T521 of subcutaneous immunotherapy
30,000 MG01 + 10,000 T521	30,000 MG01 +10,000 T521	30,000 TU/mL of MG01 + 10,000 TU/mL of T521 of subcutaneous immunotherapy

Primary Outcome Measures

Name	Time	Method
RCSMS: Combined Symptoms and Medication Score of rhinitis. Combined symptom and medication score in rhinitis/rhinoconjunctivitis (RCSMS)	18 months	Evaluation of the number of symptoms and the consumption of medication necessary for the control of such symptoms in rhinitis / rhinoconjunctivitis of each subject during the pollen season and pollen peak of cupressaceae (January, February and March) and grasses (May and June), of the groups with each other and with respect to placebo.

Secondary Outcome Measures

Name	Time	Method
Symptom free days	18 months	The number of days during the trial period that the subject was free of symptoms related to the study pathologies (both rhinitis/rhinoconjunctivitis and asthma) shall be counted for each subject.
Medication free days	18 months	The number of days during the trial period that the subject has not taken any medication for symptom (both rhinitis/rhinoconjunctivitis and asthma) relief shall be counted for each subject.
Symptom score in rhinitis/rhinoconjunctivitis (RSS) during pollen season and pollen peak of grasses and cupressaceae	18 months	The rhinitis/rhinoconjunctivitis-related symptom score shall be counted throughout the trial period for each subject.
Medication score in rhinitis/rhinoconjunctivitis (RMS) during pollen season and pollen peak of grasses and cupressaceae	18 months	The rhinitis/rhinoconjunctivitis-related medication score will be counted throughout the trial period for each subject.
Combined symptom and medication score (ACSMS) during pollen season and pollen peak of grasses and cupressaceae	18 months	The combined asthma-related symptom score (ASS) and asthma-related medication score (AMS) shall be counted throughout the trial period for each subject.; The ACSMS shall range from 0 to 6.
Asthma symptom score (ASS) during pollen season and pollen peak of grasses and cupressaceae	18 months	The asthma-related symptom score shall be counted throughout the trial period for each subject. The symptoms are as follows: coughing, wheezing or whistling, choking or suffocating sensation, chest tightness; The assessment criteria for each symptom shall be as follows: 0 = No symptoms (no obvious symptoms).; 1. = Mild (trivial; the symptom is clearly present but not bothersome).; 2. = Moderate (annoying, but not disabling or intolerable).; 3. = Severe (disabling and/or intolerable). The asthma symptom score (ASS) will be the sum of the 4 asthma symptoms divided by 4. The final score will vary from 0 to 3.
Asthma Medication Score (AMS) during pollen season and pollen peak of grasses and cupressaceae	18 months	The asthma-related medication score will be counted throughout the trial period for each subject. The medication will be scored based on the therapeutic step in which the drugs are included in the GEMA 5.0 and GINA 2020 guidelines. The scoring approach is detailed in the article entitled 'Combination of Allergic Asthma Symptom and Medication Scores in Allergen Immunotherapy Trials: A Proposal'
Asthma and rhinitis/rhinoconjunctivitis symptom score (ARSS) during pollen season and pollen peak of grasses and cupressaceae	18 months	The asthma-related (ASS) and rhinitis/rhinoconjunctivitis (RSS) symptom scores shall be counted throughout the trial period for each subject.; The ARSS shall range from 0 to 6.
Asthma and rhinitis/rhinoconjunctivitis medication score (ARMS) during pollen season and pollen peak of grasses and cupressaceae	18 months	The asthma-related medication score (AMS) and rhinitis/rhinoconjunctivitis score (RMS) shall be counted throughout the trial period for each subject.; The ARMS shall range from 0 to 6.
Combined symptom and medication score in asthma and rhinitis/rhinoconjunctivitis (ARCSMS) during pollen season and pollen peak of grasses and cupressaceae	18 months	The combined asthma-related symptom and medication score (ACSMS) and rhinitis/rhinoconjunctivitis (RCSMS) shall be counted throughout the trial period for each subject.; The ARCSMS shall range from 0 to 12.
Asthmatic exacerbations	18 months	Time to first occurrence of asthmatic exacerbation, number, duration and severity will be analysed.
Visual Analogue Scale (VAS)	18 months	Visual Analogue Scale in which the subject has to indicate in a straight line of 10cm how he/she feels regarding to his allergy symptoms. Being left side (0) = very bad and right side (10) = very well
Immunological parameters	18 months	Total IgE, specific IgE and specific IgG4 are analysed during screening and final visit.; The determination of grasses shall be carried out on Phleum pratense. The determination of immunological parameters shall be carried out by analysis of the whole or total extract and not by molecular components.
Quality of life associated with asthma (ACQ-6)	18 months	The quality of life associated with asthma will be measured following the ACQ questionnaire.; The ACQ questionnaire consists of 6 questions (ACQ-6). In questions 1-6, patients recall their experience during the last 7 days and answer using a scale of 7 points (from 0 = fully controlled to 6 = extremely poorly controlled). The questionnaire score is the mean of the 6 responses (ACQ-6).; The interpretation of the scores is as follows: Less than or equal to 0.75: Adequate control of asthma From 0.75 to 1.50: Partially controlled asthma More than 1.50: Inadequate asthma control
Quality of life associated with rhinitis (ESPRINT-15)	18 months	The quality of life associated with rhinitis will be measured following the test ESPRINT-15.; The scoring of the questionnaire will be carried out as follows: The global sum of the scores (ranging from "0 = nothing has bothered me" to "6 = it has bothered me a lot") of the 14 items plus the score given in the general questionnaire (ranging from "0 = Excellent" to "4 = Bad"). This sum is divided by the total number of items (15 items).; The interpretation of the scores is between 0 (low impact) and 6 (high impact).
Health resource consumption	18 months	Counting the Health resource consumption related to the study pathology: visits to specialists, telephone calls, test and analyses.; Recording of health resource consumption will be carried out at all study visits, from screening to final visit or additional final visit, if applicable.
Safety parameters	18 months	Number of participants with treatment-related adverse events as assessed by T521+MG01-SIT026.; Comparison between the beginning and end of the trial and among active groups and placebo

Trial Locations

Locations (26)

Hospital Recoletas Felipe Ii; 🇪🇸 Valladolid, Castilla Y León, Spain

Hospital Universitario Principe de Asturias; 🇪🇸 Alcalá De Henares, Comunidad De Madrid, Spain

Hospital Cruz Roja Madrid; 🇪🇸 Madrid, Comunidad De Madrid, Spain

Clínica Privada Dres Ojeda; 🇪🇸 Madrid, Comunidad De Madrid, Spain

Hospital Universitario Puerta de Hierro; 🇪🇸 Majadahonda, Comunidad De Madrid, Spain

Cedt de Tarancón; 🇪🇸 Tarancón, Cuenca, Spain

Hospital U. Fundación Alcorcón; 🇪🇸 Alcorcón, Madrid, Spain

Clínica Privada Murcia; 🇪🇸 Murcia, Región De Murcia, Spain

Fundación Hospital Sant Pere Claver; 🇪🇸 Barcelona, Spain

Clínica privada Burgos; 🇪🇸 Burgos, Spain

Hospital Universitario de Burgos; 🇪🇸 Burgos, Spain

Hospital General de Villalba; 🇪🇸 Collado-Villalba, Spain

Clinica privada; 🇪🇸 León, Spain

Clínica Subiza; 🇪🇸 Madrid, Spain

Hospital Carlos III (antiguo CAP José Marva); 🇪🇸 Madrid, Spain

Clínica Privada; 🇪🇸 Zaragoza, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital Infanta Elena; 🇪🇸 Madrid, Spain

Centro médico Saluddia; 🇪🇸 Madrid, Spain

Centro Médico Iza (Clínica Privada Madrid); 🇪🇸 Madrid, Spain

Consulta Privada; 🇪🇸 Palencia, Spain

Hospital Clínico de Salamanca; 🇪🇸 Salamanca, Spain

Hospital General Universitario de Segovia; 🇪🇸 Segovia, Spain

Clinica Privada Soria; 🇪🇸 Soria, Spain

Hospital Nuestra Señora de Sonsoles; 🇪🇸 Ávila, Spain