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

A RDPC, Prospective, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of SCIT in Patients With Rhinitis With or Without Mild to Moderate Asthma Sensitized to Cupressaceae and Grasses.

A Randomized, Double-Blinded, Placebo-Controlled, Prospective, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Immunotherapy in Patients With Rhinitis 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

Double blind, multicenter, parallel, placebo controlled study. It includes 150 subjects sensitised to cupressaceae and grass pollen, from 14 to 65 years of age. Medication treatment during 1 year. The main outcome: CSMS

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

Contacts and Locations

• Study Contact: Name: Pedro Carretero, MD; Phone Number: 947 28 18 00; Email: pcarreteroa@gmail.com
• Study Contact Backup: Name: Miguel Casanovas, MD PhD; Phone Number: 916510010; Email: mcasanovas@inmunotek.com

Study Locations

• Spain
  • Barcelona, Spain, 08004
    • Recruiting
    • Fundación Hospital Sant Pere Claver
    • Principal Investigator: Helena Hermida Clarena, DM
  • Burgos, Spain, 09006
    • Recruiting
    • Hospital Universitario de Burgos
    • Contact: Pedro Carretero, MD; Phone Number: 947 28 18 00
    • Principal Investigator: Pedro Carretero Anibarro, MD
    • 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: Laura Manzanedo Ortega, MD
    • Sub-Investigator: Sonia del Pozuelo Aparicio, MD
  • León, Spain, 24001
    • Active, not recruiting
    • Clinica privada
  • Madrid, Spain, 28006
    • Recruiting
    • Clínica Subiza
    • Principal Investigator: Javier Subiza Garrido-Lestache
    • Sub-Investigator: Concepción Barjau Buj
  • Madrid, Spain, 28020
    • Active, not recruiting
    • Cap José Marvá
  • Madrid, Spain, 28035
    • Active, not recruiting
    • Clinica privada
  • Palencia, Spain, 34002
    • Recruiting
    • Clinica privada
    • Principal Investigator: Izaskun Leanizbarrutia De Bizkarralegorra, DM
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Clinico De Salamanca
    • Principal Investigator: Teresa Gracia Bara, DM
    • Sub-Investigator: Ignacio Jesús Dávila González, DM
  • Soria, Spain, 42002
    • Active, not recruiting
    • Clinica Privada Soria
  • Zaragoza, Spain, 50004
    • Not yet recruiting
    • Clínica Privada Zaragoza
    • Principal Investigator: Ignacio Javier Pérez-Camo Choliz, DM
  • Castilla Y León
    • Valladolid, Castilla Y León, Spain, 47003
      • Active, not recruiting
      • Hospital Recoletas Felipe Ii
  • Comunidad De Madrid
    • Alcalá De Henares, Comunidad De Madrid, Spain, 28805
      • Recruiting
      • Hospital Universitario Príncipe de Asturias
      • Principal Investigator: José Barbarroja Escudero, DM
    • Madrid, Comunidad De Madrid, Spain, 28003
      • Recruiting
      • Hospital Cruz Roja Madrid
      • Principal Investigator: Jose Julio Laguna, DM
    • Madrid, Comunidad De Madrid, Spain
      • Recruiting
      • Clinica Ojeda
      • Principal Investigator: Pedro Ojeda, DM
    • Majadahonda, Comunidad De Madrid, Spain, 28222
      • Active, not recruiting
      • Hospital Universitario Puerta de Hierro
  • Cuenca
    • Tarancon, Cuenca, Spain, 16400
      • Active, not recruiting
      • Cedt de Tarancón
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Active, not recruiting
      • Hospital U. Fundación Alcorcón
  • Región De Murcia
    • Murcia, Región De Murcia, Spain, 30006
      • Active, not recruiting
      • Clínica Privada Murcia

Participation Criteria

Eligibility Criteria

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

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 grass pollen extract (Phleum pratense, Holcus lanatus, Dactylis glomerata, Poa pratensis, Festuca elatior, Lolium perenne) or to a one extract of the mixture and to a cupressaceae extract.
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
CSMS: Combined Symptoms and Medication Score, asthma and rhinitis.	Evaluation of the number of symptoms and the consumption of medication necessary for the control of such symptoms in asthma and rhinitis / rhinoconjunctivitis of each subject during the trial, of the groups with each other and with respect to placebo.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asthmatic exacerbations	Time elapsed until the first appearance of asthmatic exacerbations, number, duration and severity.	12 months
Quality of life associated with rhinitis	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).	12 months
Medication free days	Both rhinitis/rhinoconjunctivitis and asthma	12 months
Symptom free days	Both rhinitis/rhinoconjunctivitis and asthma	12 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	12 months
Quality of life associated with asthma	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	12 months
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	12 months
Health resource consumption	Counting the Health resource consumption: visits to specialists, telephone calls, test and analyses.	12 months

Collaborators and Investigators

• Sponsor: Inmunotek S.L.
• Investigators: Principal Investigator: Pedro Carretero, MD, Hospital Universitario de Burgos

Publications and helpful links

General Publications

• 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 (Anticipated): December 1, 2023
• Study Completion (Anticipated): April 1, 2024

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): November 21, 2022
• Last Update Submitted That Met QC Criteria: November 18, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Allergy; Immunotherapy; Rhinitis/ Rhinoconjunctivitis; Mild to moderate asthma; Grass; cupressaceae
• 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: 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