Clinical trial NCT04898283: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rhinitis, Allergic
Rhinoconjunctivitis
Asthma, Allergic
Keywords: Rhinitis/ Rhinoconjunctivitis
Mild to moderate asthma
Allergy
Immunotherapy
Grass
cupressaceae
Lead sponsor: Inmunotek S.L.
Sponsor class: INDUSTRY
First posted: 2021-05-24
Enrollment: 180
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, multicentre, parallel-group study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: RCSMS: Combined Symptoms and Medication Score of rhinitis. Combined symptom and medication score in rhinitis/rhinoconjunctivitis (RCSMS)
timeFrame: 18 months
Secondary outcomes:
measure: Symptom free days
timeFrame: 18 months
measure: Medication free days
timeFrame: 18 months
measure: Symptom score in rhinitis/rhinoconjunctivitis (RSS) during pollen season and pollen peak of grasses and cupressaceae
timeFrame: 18 months
measure: Medication score in rhinitis/rhinoconjunctivitis (RMS) during pollen season and pollen peak of grasses and cupressaceae
timeFrame: 18 months
measure: Combined symptom and medication score (ACSMS) during pollen season and pollen peak of grasses and cupressaceae
timeFrame: 18 months
measure: Asthma symptom score (ASS) during pollen season and pollen peak of grasses and cupressaceae
timeFrame: 18 months
measure: Asthma Medication Score (AMS) during pollen season and pollen peak of grasses and cupressaceae
timeFrame: 18 months
measure: Asthma and rhinitis/rhinoconjunctivitis symptom score (ARSS) during pollen season and pollen peak of grasses and cupressaceae
timeFrame: 18 months
measure: Asthma and rhinitis/rhinoconjunctivitis medication score (ARMS) during pollen season and pollen peak of grasses and cupressaceae
timeFrame: 18 months
measure: Combined symptom and medication score in asthma and rhinitis/rhinoconjunctivitis (ARCSMS) during pollen season and pollen peak of grasses and cupressaceae
timeFrame: 18 months
measure: Asthmatic exacerbations
timeFrame: 18 months
measure: Visual Analogue Scale (VAS)
timeFrame: 18 months
measure: Immunological parameters
timeFrame: 18 months
measure: Quality of life associated with asthma (ACQ-6)
timeFrame: 18 months
measure: Quality of life associated with rhinitis (ESPRINT-15)
timeFrame: 18 months
measure: Health resource consumption
timeFrame: 18 months
measure: Safety parameters
timeFrame: 18 months
Other outcomes:
Locations:
city: Valladolid
country: Spain
facility: Hospital Recoletas Felipe Ii
state: Castilla Y León
city: Alcalá De Henares
country: Spain
facility: Hospital Universitario Principe de Asturias
state: Comunidad De Madrid
city: Madrid
country: Spain
facility: Hospital Cruz Roja Madrid
state: Comunidad De Madrid
city: Madrid
country: Spain
facility: Clínica Privada Dres Ojeda
state: Comunidad De Madrid
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Comunidad De Madrid
city: Tarancón
country: Spain
facility: Cedt de Tarancón
state: Cuenca
city: Alcorcón
country: Spain
facility: Hospital U. Fundación Alcorcón
state: Madrid
city: Murcia
country: Spain
facility: Clínica Privada Murcia
state: Región De Murcia
city: Barcelona
country: Spain
facility: Fundación Hospital Sant Pere Claver
city: Burgos
country: Spain
facility: Clínica privada Burgos
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Collado-Villalba
country: Spain
facility: Hospital General de Villalba
city: León
country: Spain
facility: Clinica privada
city: Madrid
country: Spain
facility: Clínica Subiza
city: Madrid
country: Spain
facility: Hospital Carlos III (antiguo CAP José Marva)
city: Madrid
country: Spain
facility: Clínica Privada
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Infanta Elena
city: Madrid
country: Spain
facility: Centro médico Saluddia
city: Madrid
country: Spain
facility: Centro Médico Iza (Clínica Privada Madrid)
city: Palencia
country: Spain
facility: Consulta Privada
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
city: Segovia
country: Spain
facility: Hospital General Universitario de Segovia
city: Soria
country: Spain
facility: Clinica Privada Soria
city: Zaragoza
country: Spain
facility: Clínica Privada
city: Ávila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
Study officials:
affiliation: Clínica privada Dres Ojeda
name: Pedro Ojeda, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.