Efficacy and Safety Evaluation for the Treatment of Allergy Against Grass and Olive Pollen

A Randomized, Double-Blinded, Placebo-Controlled, Prospective, Multicenter CT to Evaluate Efficacy and Safety of Subcutaneous Immunotherapy in Subjects With Rhinitis With/Without Mild to Moderate Asthma Sensitized to Olive and Grass Pollen

Prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial of efficacy and safety with subcutaneous immunotherapy in patients with mild to moderate rhinitis / rhinoconjunctivitis with or without mild to moderate asthma sensitized to grasses and olive

Study Overview

• Status: Recruiting
• Conditions: Rhinitis, Allergic; Rhinoconjunctivitis; Asthma, Allergic
• Intervention / Treatment: Biological: 10,000 MG01 + 10,000 T517; Biological: 30,000 MG01 + 10,000 T517; Other: Placebo

Detailed Description

Double blind, multicenter, parallel, placebo controlled study. It includes 180 subjects sensitised to olea and grass pollen with mild to moderate rhinitis / rhinoconjunctivitis with or without mild to moderate asthma, from 12 to 65 years of age. Medication treatment during 1 year. The main outcome: CSMS

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

Contacts and Locations

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

Study Locations

• Spain
  • Albacete, Spain, 02003
    • Withdrawn
    • Private Practice
  • Badajoz, Spain, 06001
    • Recruiting
    • Clinica Dermatologica Y Alergia
    • Principal Investigator: Irán Sánchez Ramos, MD
  • Barcelona, Spain, 08028
    • Recruiting
    • Hospital Universitario Dexeus
    • Principal Investigator: Elena Botey Faraudo, MD
  • Córdoba, Spain, 14004
    • Recruiting
    • Hospital Quirónsalud Córdoba
    • Principal Investigator: Ignacio García Nuñez, MD
  • Granada, Spain, 18016
    • Recruiting
    • Hospital Universitario Clínico San Cecilio
    • Principal Investigator: José Fernando Florido López, MD
    • Sub-Investigator: María José Rojas Vilchez, MD
    • Sub-Investigator: María Ángeles Lara Jiménez, MD
    • Sub-Investigator: Carolina Mérida Fernández, MD
    • Sub-Investigator: Enrique Martín Casañez, MD
    • Sub-Investigator: Araceli Castro, MD
  • Jaén, Spain, 23007
    • Recruiting
    • Hospital Universitario de Jaén
    • Sub-Investigator: Carmen Laura Cañada Porta, MD
    • Sub-Investigator: Juan Luis Anguita Carazo, MD
    • Sub-Investigator: María Antonia Navarrete del Pimo, MD
    • Sub-Investigator: Sara Anaya Anaya, MD
    • Principal Investigator: Manuel Alcántara Villar, MD
  • Lleida, Spain, 25198
    • Recruiting
    • Hospital Universitari Santa María
    • Principal Investigator: Eva Alcoceba Borrás, MD
  • Madrid, Spain, 28006
    • Recruiting
    • Clínica Subiza
    • Principal Investigator: Javier Subiza Garrido-Lestache, MD
    • Sub-Investigator: Concepción Barjau Buj, MD
  • Madrid, Spain, 28020
    • Recruiting
    • Cap José Marvá
    • Principal Investigator: Margarita Tomás Pérez, MD
    • Sub-Investigator: Javier Contreras Porta, MD
    • Sub-Investigator: Juan Alberto Luna Porta, MD
    • Sub-Investigator: Leticia de las Vecillas, MD
  • Madrid, Spain, 28001
    • Terminated
    • Private Practice
  • Madrid, Spain, 28003
    • Recruiting
    • Hospital Universitario Cruz Roja
    • Principal Investigator: JOSE JULIO LAGUNA, MD
    • Sub-Investigator: Cosmin Boteau, MD
  • Madrid, Spain, 28006
    • Recruiting
    • Clínica de Asma y Alergia en Madrid | CLÍNICA OJEDA
    • Principal Investigator: Pedro Ojeda, MD
    • Sub-Investigator: David Baquero, MD
  • Madrid, Spain, 28933
    • Recruiting
    • Hospital Universitario Rey Juan carlos
    • Principal Investigator: Pilar Gajate Fernández, MD
  • Murcia, Spain
    • Recruiting
    • Private Practice
    • Principal Investigator: Antonio Carbonell, MD
    • Sub-Investigator: Yulia Petryk Petryk, MD
  • Málaga, Spain, 29004
    • Recruiting
    • Hospital Quirónsalud Málaga
    • Principal Investigator: Leticia Herrero, DM
  • Málaga, Spain
    • Recruiting
    • Private Practice
    • Principal Investigator: Manuel Barceló, DM
  • Palencia, Spain, 34001
    • Recruiting
    • Private Practice
    • Principal Investigator: Izaskun Leanizbarrutia De Bizkarralegorra, MD
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Virgen del Rocio
    • Principal Investigator: Joaquín Quiralte Enriquez, MD
    • Sub-Investigator: Yolanda Puente Crespo, MD
    • Sub-Investigator: María del Robledo Ávila Castellano, MD
    • Sub-Investigator: Carmen Rodríguez Pozo, Nurse
    • Sub-Investigator: Esteban Romero Rueda, Nurse
  • Sevilla, Spain, 41014
    • Recruiting
    • Hospital Viamed Santa Angela De la Cruz
    • Principal Investigator: MÓNICA DONADO NORTES, MD
  • Toledo, Spain, 45005
    • Withdrawn
    • Private Practice
  • Valladolid, Spain, 47003
    • Recruiting
    • Hospital Recoletas Felipe Ii
    • Principal Investigator: Alicia Alonso, DM
  • Comunidad De Madrid
    • Alcalá De Henares, Comunidad De Madrid, Spain, 28805
      • Recruiting
      • Hospital Universitario Príncipe de Asturias
      • Principal Investigator: José Barbarroja, MD
      • Sub-Investigator: Mª José Sánchez González, MD
      • Sub-Investigator: Ana Laiseca Antón
  • Cuenca
    • Tarancon, Cuenca, Spain, 16400
      • Recruiting
      • Cedt de Tarancón
      • Principal Investigator: ANTONIO MORENO FERNÁNDEZ, MD
  • Madrid
    • Tres Cantos, Madrid, Spain, 28760
      • Recruiting
      • Centro Médico Iza
      • Contact: Diana Pérez Alzate
      • Principal Investigator: Diana Pérez Alzate, MD
    • Valdemoro, Madrid, Spain, 28342
      • Recruiting
      • Hospital Infanta Elena
      • Principal Investigator: FRANCISCO JAVIER RUIZ HORNILLOS, DM
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Clínico Universitario Virgen de Arrixaca
      • Principal Investigator: PAOLA CARRILLO, DM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 63 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject who has signed the informed consent.
2. Subjects of both sexes aged between 12 and 65 years.
3. Subjects with confirmed clinical history of inhalational allergy (rhinitis and / or moderate-severe intermittent or persistent rhinoconjunctivitis according to the ARIA classification with or without intermittent or persistent controlled mild-moderate asthma according to the GEMA 5.0 classification caused by grass and olive allergy. The diagnosis of asthma will be valid from 12 months prior to signing the informed consent
4. Subjects with a positive prick test (higher papule diameter ≥ 5 mm) to a standardized extract of pollen from grasses (Phleum pratense, Holcus lanatus, Dactylis glomerata, Poa pratensis, Festuca elatior, Lolium perenne), or one of the components of the mixture and an olive extract.
5. Specific IgE (CAP or Immulite) against a mixture of grasses or against one of the components of the mixture of grasses, preferably Phleum pratense and olive or one of the molecular components of allergenic sources with a value > 3,5 KU / L.
6. Women of childbearing age (from menarche) should submit a urine pregnancy test with a negative result at the time of joining the trial.
7. Women of childbearing potential, and men 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 dosage regimen.
9. Subjects who have a smartphone to record symptoms 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 polysensitized to other aeroallergens with the exception of epithelia with occasional exposure and symptoms
2. Subjects polysensitized to other aeroallergens with the exception non-seasonal pollens with grasses and olive
3. Subjects who have received prior immunotherapy in the preceding 5 years to any aeroallergens.
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 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 presented a serious secondary reaction during the performance of diagnostic skin tests using the prick test.
7. Subjects under treatment with ß-blockers.
8. Clinically unstable subjects at the time of enrolment in the trial (acute asthma exacerbation, respiratory infection, feverish process, acute urticaria, etc.).
9. Subjects with active chronic urticaria, severe dermographism, severe atopic dermatitis, sunburns, 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 the administration of adrenaline is contraindicated (hyperthyroidism, HT, heart disease, etc.).
11. Subjects with some other disease not related to moderate rhinoconjunctivitis or asthma, but of potential severity and that may interfere with treatment and follow-up (epilepsy, psychomotor disorder, uncontrolled diabetes, malformations, multiple operations, kidney disease,).
12. Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumor diseases or with a diagnosis of immunodeficiencies.
13. Subject whose condition prevents him / her from offering cooperation and who has severe psychiatric disorders.
14. Subjects with a known allergy to other investigational drug components other than the allergen.
15. Subjects with diseases of the lower respiratory tract 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
Placebo Comparator: Placebo subcutaneous; The same solution and presentation as the active treatment, but without active ingredients.	Other: Placebo; The same solution and presentation as the active treatment, but without active ingredients
Experimental: 10,000 MG01 + 10,000 T517; 10,000 TU/mL of MG01 + 10,000 TU/mL of T517 of subcutaneous immunotherapy	Biological: 10,000 MG01 + 10,000 T517; 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 Olea (Olea europaea), adsorbed on aluminum hydroxide. The other ingredients are: sodium chloride (0.9%), phenol (0.4%) and water for injections; Other Names: Grasses and olea 10,000
Experimental: 30,000 MG01 + 10,000 T517; 30,000 TU/mL of MG01 + 10,000 TU/mL of T517 of subcutaneous immunotherapy	Biological: 30,000 MG01 + 10,000 T517; 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 Olea (Olea europaea), adsorbed on aluminum hydroxide. The other ingredients are: sodium chloride (0.9%), phenol (0.4%) and water for injections; Other Names: Grasses and olea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSMS: Combined Symptoms and Medication Score	Overall score of symptoms and medication throughout the trial. The minimum score is cero and maximum six, per day	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication-free days	Number of days that the subjects need no medication	12 months
Symptom-free days	Number of days that the subjects have no symptom	12 months
Security parameters	Global rate and severity of AE per administration and per subject	12 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 very bad and right side very well	12 months
Quality of life rhinitis test	Quality of life rhinitis test (ESPRINT-15)	12 months
Quality of life asthma test	Control of asthma by Asthma Control Quality questionnaire	12 months
Health resources	For each patient, the number of times that due to allergy symptoms has done the following will be counted: Have visited the GP, Have made an unscheduled visit to the specialist, Has gone to the emergency room, Has been hospitalized, Have needed to contact the doctor by phone	12 months
Immunological parameters	Analyses of total and specific IgE, specific Ig G4	12 months
Adverse Reactions	Local and systemic reactions and any medication administered for the treatment of AR	12 months
Asthmatic exacerbations	Time elapsed until the first appearance of asthmatic exacerbations	12 months

Collaborators and Investigators

• Sponsor: Inmunotek S.L.
• Investigators: Study Chair: Irán Sánchez, Private Site

Publications and helpful links

General Publications

• Subiza J, Feliu A, Subiza JL, Uhlig J, Fernandez-Caldas E. Cluster immunotherapy with a glutaraldehyde-modified mixture of grasses results in an improvement in specific nasal provocation tests in less than 2.5 months of treatment. Clin Exp Allergy. 2008 Jun;38(6):987-94. doi: 10.1111/j.1365-2222.2008.02995.x. Epub 2008 Apr 25.
• Klimek L, Uhlig J, Mosges R, Rettig K, Pfaar O. A high polymerized grass pollen extract is efficacious and safe in a randomized double-blind, placebo-controlled study using a novel up-dosing cluster-protocol. Allergy. 2014 Dec;69(12):1629-38. doi: 10.1111/all.12513. Epub 2014 Oct 6.
• 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): June 14, 2021
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Allergy; Rhinitis/ Rhinoconjunctivitis; Mild to moderate asthma; Grasses; Olea
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Otorhinolaryngologic Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Asthma; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: DMV03-SIT-027

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