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

Official title

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

Overview

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.

Interventions

• 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
• 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.
• Other Placebo subcutaneous
  The same solution and presentation as the active treatment, but without active ingredients

Primary outcome measures

• RCSMS: Combined Symptoms and Medication Score of rhinitis. Combined symptom and medication score in rhinitis/rhinoconjunctivitis (RCSMS) [Time frame: 18 months]

Secondary outcome measures (12)

• Symptom free days [Time frame: 18 months]
• Medication free days [Time frame: 18 months]
• Symptom score in rhinitis/rhinoconjunctivitis (RSS) during pollen season and pollen peak of grasses and cupressaceae [Time frame: 18 months]
• Medication score in rhinitis/rhinoconjunctivitis (RMS) during pollen season and pollen peak of grasses and cupressaceae [Time frame: 18 months]
• Combined symptom and medication score (ACSMS) during pollen season and pollen peak of grasses and cupressaceae [Time frame: 18 months]
• Asthma symptom score (ASS) during pollen season and pollen peak of grasses and cupressaceae [Time frame: 18 months]
• Asthma Medication Score (AMS) during pollen season and pollen peak of grasses and cupressaceae [Time frame: 18 months]
• Asthma and rhinitis/rhinoconjunctivitis symptom score (ARSS) during pollen season and pollen peak of grasses and cupressaceae [Time frame: 18 months]
• Asthma and rhinitis/rhinoconjunctivitis medication score (ARMS) during pollen season and pollen peak of grasses and cupressaceae [Time frame: 18 months]
• Combined symptom and medication score in asthma and rhinitis/rhinoconjunctivitis (ARCSMS) during pollen season and pollen peak of grasses and cupressaceae [Time frame: 18 months]
• Asthmatic exacerbations [Time frame: 18 months]
• Visual Analogue Scale (VAS) [Time frame: 18 months]

Eligibility criteria

Inclusion criteria

• Written informed consent.
• Aged between 12 and 65, both genders
• 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.
• 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.
• Specific IgE > 3,5 KU/L , against grass (preferably Phleum pratense) and cupressaceae pollen (InmunoCAP® o Immulite).
• Women of childbearing age (from menarche) must present a urine pregnancy test with a negative result at the time of joining the trial.
• 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.
• Subjects capable of complying with the dosing regimen.
• Subjects who own a smartphone for symptom registration and medication.
• 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
• 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

• Subjects with positive prick test to other aeroallergens except for sensitisation to epithelia with occasional exposure and symptoms.
• Subjects with positive prick test to other aeroallergens except for sensitisation to pollen noncoseasonal with cupressus or grasses.
• 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.
• 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.
• 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.
• Subjects who have previously had a severe secondary reaction during the prick test diagnostic skin test.
• Subjects treated with beta-blockers.
• Clinically unstable subjects at the time of inclusion in the trial (acute asthmatic exacerbation, respiratory infection, febrile process, acute urticaria, etc.).
• 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.
• Subjects who have any pathology in which adrenaline administration is contraindicated (hyperthyroidism, HTN, heart disease, etc.).
• 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,).
• Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumor diseases or with a diagnosis of immunodeficiencies.
• Subject whose condition prevents from offering cooperation and/ or who has severe psychiatric disorders.
• Subjects with a known allergy to components of the investigational medicinal product other than the allergen.
• Subjects with lower respiratory diseases other than asthma such as emphysema or bronchiectasis.
• Subjects who are direct relatives of the researchers.
• Pregnant or lactating women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Spain · 27 centers

• Hospital Recoletas Felipe Ii — Valladolid
• Cedt de Tarancón — Tarancón
• Hospital Universitario Principe de Asturias — Alcalá de Henares
• Hospital U. Fundación Alcorcón — Alcorcón
• Hospital Cruz Roja Madrid — Madrid
• Clínica Privada Dres Ojeda — Madrid
• Hospital Universitario Puerta de Hierro — Majadahonda
• Clínica Privada Murcia — Murcia
• … and 19 more centers

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. PMID 27939406
• 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. PMID 33498057

Identifiers

NCT: NCT04898283 · DMV02-SIT-026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗