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

Prospective, Multicentre, Doubleblind, Placebo-controlled RCT to Evaluate Efficacy and Safety With SC Immunotherapy in Patients With Rhinitis/Rhinoconjunctivitis With or Without Mild to Moderate Asthma Sensitised to Grasses and Cupressaceae

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.

Study Overview

• Status: Recruiting
• Conditions: Rhinitis, Allergic; Rhinoconjunctivitis; Asthma, Allergic
• Intervention / Treatment: Biological: 10,000 MG01 +10,000 T521; Biological: 30,000 MG01 +10,000 T521; Other: Placebo subcutaneous

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 Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Raquel Caballero; Phone Number: +34 607600638; Email: rcaballero@inmunotek.com
• Study Contact Backup: Name: Miguel Casanovas, MD PhD; Phone Number: 0034 +34 912908942; Email: mcasanovas@inmunotek.com

Study Locations

• Spain
  • Barcelona, Spain, 08004
    • Withdrawn
    • Fundación Hospital Sant Pere Claver
  • Burgos, Spain, 09006
    • Recruiting
    • Hospital Universitario de Burgos
    • Sub-Investigator: Natalia Sofía Perea Lam, MD
    • Sub-Investigator: Carmen Reinares Ten, MD
    • Sub-Investigator: Patricia Alloza Gómez, MD
    • Sub-Investigator: Reyes Pérez Giménez, MD
    • Sub-Investigator: Sonia del Pozuelo Aparicio, MD
    • Contact: Laura Manzanedo, MD; Phone Number: +34 947281800; Email: lmanzanedo@saludcastillayleon.es
    • Principal Investigator: Laura Manzanedo Ortega, MD
  • Burgos, Spain, 09004
    • Withdrawn
    • Clínica privada Burgos
  • Collado-Villalba, Spain, 28400
    • Not yet recruiting
    • Hospital General de Villalba
    • Contact: Ignacio Esteban Gorgojo, MD; Phone Number: +34 658 934 085; Email: igestebang@gmail.com
  • León, Spain, 24003
    • Withdrawn
    • Clinica privada
  • Madrid, Spain, 28034
    • Not yet recruiting
    • Hospital Universitario Ramon y Cajal
    • Principal Investigator: David González de Olano, MD
    • Contact: David González de Olano, MD; Phone Number: +34 913368000; Email: dgolano@yahoo.es
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
    • Contact: Diana Betancor Pérez, MD; Phone Number: +34 915504800; Email: diana.betancor@quironsalud.es
    • Principal Investigator: Diana Betancor Pérez, MD
  • Madrid, Spain, 28029
    • Withdrawn
    • Hospital Carlos III (antiguo CAP José Marva)
  • Madrid, Spain, 28034
    • Withdrawn
    • Clinica privada
  • Madrid, Spain, 28522
    • Recruiting
    • Centro médico Saluddia
    • Contact: Beatriz Huertas Barbudo, MD; Phone Number: +34 917372953; Email: huertasb@gmail.com
    • Principal Investigator: Beatriz Huertas Barbudo, MD
  • Madrid, Spain, 28760
    • Recruiting
    • Centro Médico Iza (Clínica Privada Madrid)
    • Contact: Diana Victoria Pérez Alzate, MD; Phone Number: +34 918046602; Email: dianatoria@hotmail.com
    • Principal Investigator: Diana Pérez, MD
  • Madrid, Spain, 28006
    • Active, not recruiting
    • Clínica Subiza
  • Madrid, Spain, 28342
    • Not yet recruiting
    • Hospital Infanta Elena
    • Contact: Francisco Javier Ruiz Hornillos, MD; Phone Number: +34 918948410; Email: jrornillod@gmail.com
    • Principal Investigator: Francisco Javier Ruiz Hornillos, MD
  • Palencia, Spain, 34001
    • Completed
    • Consulta Privada
  • Salamanca, Spain, 37007
    • Active, not recruiting
    • Hospital Clínico de Salamanca
  • Segovia, Spain, 40002
    • Not yet recruiting
    • Hospital General Universitario de Segovia
    • Contact: María Mercedes Fuentes Cuesta, MD PhD; Phone Number: +34 629 870 557; Email: fuentescuesta@yahoo.es
    • Principal Investigator: María Mercedes Fuentes Cuesta, MD PhD
    • Sub-Investigator: Ignacio González Rodríguez, MD
    • Sub-Investigator: Rosa María Blanco González, MD
    • Sub-Investigator: María Polo López, MD
  • Soria, Spain, 42005
    • Withdrawn
    • Clinica Privada Soria
  • Zaragoza, Spain, 50004
    • Withdrawn
    • Clinica privada
  • Ávila, Spain, 05071
    • Not yet recruiting
    • Hospital Nuestra Señora de Sonsoles
    • Contact: Sara Acero Sainz, MD; Phone Number: +34 920 358 000; Email: sacero@saludcastillayleon.es
    • Principal Investigator: Sara Acero Sainz, MD
    • Sub-Investigator: María Aránzazu Jiménez Blanco, MD
    • Sub-Investigator: Carlos Domingo González, MD
  • Castilla Y León
    • Valladolid, Castilla Y León, Spain, 47003
      • Recruiting
      • Hospital Recoletas Felipe Ii
      • Contact: Alicia Alonso, MD; Phone Number: +34 983358000; Email: aliciaalonsogomez@gmail.com
      • Principal Investigator: Alicia Alonso, MD
  • Comunidad De Madrid
    • Alcalá De Henares, Comunidad De Madrid, Spain, 28806
      • Completed
      • Hospital Universitario Príncipe de Asturias
    • Madrid, Comunidad De Madrid, Spain, 28003
      • Recruiting
      • Hospital Cruz Roja Madrid
      • Principal Investigator: Jose Julio Laguna, MD
      • Contact: Jose Julio Laguna, MD; Phone Number: +34 914538300; Email: josejuliolaguna@gmail.com
      • Sub-Investigator: María Luisa Sánchez Millán, MD
      • Sub-Investigator: Cosmin Boteanu, MD
      • Sub-Investigator: Rosario González, MD
      • Sub-Investigator: Inmaculada Piorno, MD
    • Madrid, Comunidad De Madrid, Spain, 28006
      • Recruiting
      • Clínica Privada Dres Ojeda
      • Principal Investigator: Pedro Ojeda, MD
      • Sub-Investigator: David Baquero, MD
      • Contact: Pedro Ojeda, MD; Phone Number: +34 915623262; Email: pedro.ojeda@clinicaojeda.es
      • Sub-Investigator: Isabel Ojeda, MD
      • Sub-Investigator: Gema Rubio, MD
      • Sub-Investigator: Beatriz Torres, MD
    • Majadahonda, Comunidad De Madrid, Spain, 28222
      • Not yet recruiting
      • Hospital Universitario Puerta de Hierro
      • Contact: Ángel Luis Villalón, MD; Phone Number: +34 911916000; Email: anluvillalon@yahoo.es
      • Principal Investigator: Ángel Luis Villalón García, MD
      • Sub-Investigator: Alfredo Iglesias Cadarso, MD
      • Sub-Investigator: Tania Sofía Dávila Teran, MD
      • Sub-Investigator: María Angélica Gutiérrez-Maturana, MD
  • Cuenca
    • Tarancón, Cuenca, Spain, 16400
      • Recruiting
      • Cedt de Tarancón
      • Principal Investigator: Antonio Moreno Fernández, MD
      • Contact: Antonio Moreno Fernández, MD; Phone Number: +34 918925373; Email: doctorertony@hotmail.com
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Recruiting
      • Hospital U. Fundación Alcorcón
      • Contact: Mª Dolores Alonso Díaz de Durana; Phone Number: +34 916219400; Email: mdolores.alonso@salud.madrid.org
      • Principal Investigator: Mª Dolores Alonso Díaz de Durana, MD
      • Sub-Investigator: Ana González Moreno, MD
      • Sub-Investigator: Ana Nieto Nieto, MD
      • Sub-Investigator: Ana Rosado Ingelmo, MD
  • Región De Murcia
    • Murcia, Región De Murcia, Spain, 30006
      • Not yet recruiting
      • Clínica Privada Murcia
      • Contact: Antonio Carbonell Martínez, MD; Phone Number: +34 968238621; Email: med018934@gmail.com
      • Principal Investigator: Antonio Carbonell Martínez, MD
      • Sub-Investigator: Yulia Petryk, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10,000 MG01 + 10,000 T521; 10,000 TU/mL of MG01 + 10,000 TU/mL of T521 of subcutaneous immunotherapy	Biological: 10,000 MG01 +10,000 T521; Purified and polymerized with glutaraldehyde allergen extract, from a mixture of grasses (Phleum pratense, Holcus lanatus, Poa pratensis, Festuca pratensis, Lolium perenne and Dactylis glomerata) and cupressaceae (Juniperus oxycedrus), adsorbed on aluminum hydroxide. The other ingredients are: sodium chloride (0.9%), phenol (0.4%) and water for injections
Experimental: 30,000 MG01 + 10,000 T521; 30,000 TU/mL of MG01 + 10,000 TU/mL of T521 of subcutaneous immunotherapy	Biological: 30,000 MG01 +10,000 T521; Purified allergen extract polymerized with glutaraldehyde, from a mixture of grasses (Phleum pratense, Holcus lanatus, Poa pratensis, Festuca pratensis, Lolium perenne and Dactylis glomerata) and cupressaceae (Juniperus oxycedrus), adsorbed on aluminum hydroxide. The other ingredients are: sodium chloride (0.9%), phenol (0.4%) and water for injections.
Placebo Comparator: Placebo subcutaneous; The same solution and presentation as the active treatment, but without active ingredients.	Other: Placebo subcutaneous; The same solution and presentation as the active treatment, but without active ingredients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RCSMS: Combined Symptoms and Medication Score of rhinitis. Combined symptom and medication score in rhinitis/rhinoconjunctivitis (RCSMS)	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.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom free days	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.	18 months
Medication free days	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.	18 months
Symptom score in rhinitis/rhinoconjunctivitis (RSS) during pollen season and pollen peak of grasses and cupressaceae	The rhinitis/rhinoconjunctivitis-related symptom score shall be counted throughout the trial period for each subject.	18 months
Medication score in rhinitis/rhinoconjunctivitis (RMS) during pollen season and pollen peak of grasses and cupressaceae	The rhinitis/rhinoconjunctivitis-related medication score will be counted throughout the trial period for each subject.	18 months
Combined symptom and medication score (ACSMS) during pollen season and pollen peak of grasses and cupressaceae	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.	18 months
Asthma symptom score (ASS) during pollen season and pollen peak of grasses and cupressaceae	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).; = Mild (trivial; the symptom is clearly present but not bothersome).; = Moderate (annoying, but not disabling or intolerable).; = 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.	18 months
Asthma Medication Score (AMS) during pollen season and pollen peak of grasses and cupressaceae	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'	18 months
Asthma and rhinitis/rhinoconjunctivitis symptom score (ARSS) during pollen season and pollen peak of grasses and cupressaceae	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.	18 months
Asthma and rhinitis/rhinoconjunctivitis medication score (ARMS) during pollen season and pollen peak of grasses and cupressaceae	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.	18 months
Combined symptom and medication score in asthma and rhinitis/rhinoconjunctivitis (ARCSMS) during pollen season and pollen peak of grasses and cupressaceae	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.	18 months
Asthmatic exacerbations	Time to first occurrence of asthmatic exacerbation, number, duration and severity will be analysed.	18 months
Visual Analogue Scale (VAS)	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	18 months
Immunological parameters	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.	18 months
Quality of life associated with asthma (ACQ-6)	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	18 months
Quality of life associated with rhinitis (ESPRINT-15)	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).	18 months
Health resource consumption	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.	18 months
Safety parameters	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	18 months

Collaborators and Investigators

• Sponsor: Inmunotek S.L.
• Investigators: Study Director: Pedro Ojeda, MD, Clínica Privada Dres Ojeda

Publications and helpful links

General Publications

• Caballero R, Grau A, Javaloyes G, Del Pozo S, Leon MA, Romero M, Casanovas M. Combination of Allergic Asthma Symptom and Medication Scores in Allergen Immunotherapy Trials: A Proposal. Int Arch Allergy Immunol. 2021;182(7):571-573. doi: 10.1159/000513543. Epub 2021 Jan 26. No abstract available.
• Guzman-Fulgencio M, Caballero R, Lara B, Mena M, Tejera M, Sastre A, Subiza JL, Fernandez-Caldas E, Casanovas M. Safety of immunotherapy with glutaraldehyde modified allergen extracts in children and adults. Allergol Immunopathol (Madr). 2017 Mar-Apr;45(2):198-207. doi: 10.1016/j.aller.2016.08.008. Epub 2016 Dec 7.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Allergy; Immunotherapy; Rhinitis/ Rhinoconjunctivitis; Mild to moderate asthma; Grass; cupressaceae
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Eye Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Nose Diseases; Otorhinolaryngologic Diseases; Conjunctival Diseases; Asthma; Conjunctivitis; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: DMV02-SIT-026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No