Clinical trial NCT04874714: Efficacy and Safety Evaluation for the Treatment of Asthma and Allergic Rhinitis/Rhinoconjunctivitis
Official title: Prospective, Randomized, Placebo-controlled, Multi-center Trial Comparing the Efficacy and Safety of Subcutaneous Immunotherapy With a Mixture of Grasses and Mites at Adequate Doses Versus Monotherapy, for the Treatment of Allergy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Allergic Rhinoconjunctivitis
Perennial Allergic Rhinitis
House Dust Mite Allergy
Pollen Allergy
Keywords: Rhinitis/ Rhinoconjunctivitis
Mild to moderate asthma
Allergy
Immunotherapy
Mite
Pollen
Vaccine
Lead sponsor: Inmunotek S.L.
Sponsor class: INDUSTRY
Collaborators: name: BioClever 2005 S.L.
name: NTS hub S.L
First posted: 2021-05-06
Enrollment: 18
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: Prospective, randomized, placebo-controlled, multi-center trial
Primary purpose: TREATMENT

Brief summary: Prospective, randomized, placebo-controlled, multicenter of 3 active treatment groups, compared to 1 placebo group, for the determination of the efficacy and safety of subcutaneous immunotherapy in patients with mild to moderate asthma and allergic rhinitis/rhinoconjunctivitis (intermittent or persistent) due to hypersensitivity to house dust mites (Dermatophagoides pteronyssinus and / or D. farinae) and grass pollen

Detailed description: Double blind, parallel placebo-controlled study. The subjects will receive medication during 11 months

Eligibility criteria: Inclusion Criteria:

1. Subjects who have signed the informed consent
2. Subjects with a confirmed medical history of asthma (intermittent or persistent mild-moderate, controlled), as defined by GEMA 5 with moderate-severe rhinitis / rhinoconjunctivitis (intermittent or persistent) according to the ARIA classification caused by polysensitization to grass pollen and mites (D. pteronyssinus and / or D. farinae). The diagnosis of asthma will be valid from 24 months prior to signing the informed consent.
3. Subjects with a positive prick test (major diameter of the papule ≥ to 5 mm) to a standardized extract of grass pollen mixture, or to one of the components of the mixture (Dactilys glomerata, Poa pratensis, Holcus lanatus, Festuca elatior, Phleum pratense and Lolium perenne) and to an extract of D. pteronyssinus and / or D. farinae. Results will be valid 12 months prior to signing the informed consent.
4. Specific IgE (CAP or Immulite) against one of the components of the mixture of grasses, preferably Phleum pratense or a mixture of grasses and mites (D. pteronyssinus and / or D. farinae) or one or more of the molecular components of allergenic sources with a value \> 3,5 KU / L. Results will be valid 12 months prior to signing the informed consent.
5. Subjects will preferably be sensitive to study allergens (Dermatophagoides and grasses). In the case of subjects sensitized to other aeroallergens, only those with the following characteristics (results valid up to 12 months prior to signing of the informed consent) can be included in the study:

   1. Subjects with a positive prick test for Blomia tropicalis and Lepidoglyphus destructor, whose maximum values of specific IgE are 3.5 KU/L and do not exceed or equal the values of the allergens of the study (Dermatophagoides and grasses).
   2. Subjects with a negative prick test to epithelium, whose specific IgE values are \< 0.35 KU/L. Subjects with occasional exposure and symptomatology to epithelium may be included with a positive prick test regardless of the value of the specific IgE.
   3. Subjects with a positive prick test for non-coestational pollens, whose maximum values of specific IgE are 17.5 KU / L and do not exceed or equal the values of the allergens of the study (Dermathophagoids and grasses) and who also do not present exacerbations in the pollen season.
6. Subjects with a negative prick test for fungi. If the specific IgE determination has been made, the result shall be \< 0,35 KU/L.
7. Subjects with a negative prick test for coestacional pollens with grasses. If the specific IgE determination has been made, the result shall be \< 0,35 KU/L.
8. Subjects aged between 12 and 65 years, inclusive.
9. Subjects capable of complying with the dosing regimen.
10. Women of childbearing age (from menarche) should submit a urine pregnancy test with a negative result at the time of enrolment in the trial.
11. Women of childbearing potential should commit to using an adequate 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.
12. Subjects who have a smartphone to record symptoms and medication.

Exclusion Criteria:

1. Subjects who have received prior immunotherapy treatment in the preceding 5 years for any aeroallergen.
2. Patients in whom immunotherapy may be the object of 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 cannot be included.
3. Subjects with severe or uncontrolled asthma, and / or with a FEV1 \<70% with respect to the reference value despite adequate pharmacological treatment at the time of inclusion in the trial.
4. Subjects who have previously presented a serious secondary reaction during the performance of diagnostic skin tests using the prick test.
5. Subjects under treatment with ß-blockers.
6. Subjects under treatment with immunosuppressive or biological drugs.
7. Clinically unstable subjects at the time of inclusion in the trial (respiratory infection, feverish process, acute urticaria, etc.).
8. Subjects with chronic urticaria in the past 2 years, severe anaphylaxis, or a history of hereditary angioedema.
9. Subjects who have any pathology in which the administration of adrenaline is contraindicated (hyperthyroidism, HT, heart disease, etc.).
10. 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, diabetes, malformations, subjects who underwent multiple surgeries, kidney disease...), according to investigator's criteria.
11. Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumour diseases or with a diagnosis of immunodeficiencies.
12. Subject whose condition prevents him / her from offering cooperation and or who resents severe psychiatric disorders, according to investigator criteria.
13. Subjects with known allergies to other investigational product components other than grass pollen or mites.
14. Subjects with diseases of the lower respiratory tract other than asthma such as emphysema or bronchiectasis.
15. Pregnant or lactating women.

Primary outcomes:
measure: CSMS: Combined Symptoms and Medication Score
timeFrame: 12 months
Secondary outcomes:
measure: Medication-free days
timeFrame: 12 months
measure: Symptom-free days
timeFrame: 12 months
measure: Respiratory function_FEV1
timeFrame: 12 months
measure: Respiratory function_PEF
timeFrame: 12 months
measure: Asthmatic exacerbations
timeFrame: 12 months
measure: Immunological parameters
timeFrame: 12 months
measure: Visual Analogue Scale (VAS)
timeFrame: 12 months
measure: Quality of life associated with rhinitis
timeFrame: 12 months
measure: Quality of life associated with asthma
timeFrame: 12 months
measure: Consumption of health resources
timeFrame: 12 months
measure: Security parameters
timeFrame: 12 months
measure: Number of Local Adverse Reactions
timeFrame: 12 months
measure: Number of Systemic Adverse Reactions
timeFrame: 12 months
measure: Number of Adverse Reactions to any medication
timeFrame: 12 months
Other outcomes:
Locations:
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Puertollano
country: Spain
facility: Hospital Santa Bárbara
state: Ciudad Real
city: Ponferrada
country: Spain
facility: Hospital el Bierzo
state: León
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña
city: Cádiz
country: Spain
facility: Centro Médico ASISA Dr. Lobatón
city: Huelva
country: Spain
facility: C.P.E. Virgen de la Cinta - Hospital Universitario Juan Ramón Jiménez
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Málaga
country: Spain
facility: Hospital Quirón Salud Málaga
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Gasteiz / Vitoria
country: Spain
facility: Hospital Universitario de Álava
state: Álava
Study officials:
affiliation: Complejo Hospitalario de Navarra
name: Ana Isabel Tabar Purroy, MD; PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.