Efficacy and Safety Evaluation for the Treatment of Asthma and Allergic Rhinitis/Rhinoconjunctivitis

NCT04874714 | Terminated Phase 3

• 2 other identifiers: DMV01-SIT-0152018-003715-22
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 13

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

Conditions

Allergic Rhinoconjunctivitis; Perennial Allergic Rhinitis; House Dust Mite Allergy; Pollen Allergy

Keywords

Rhinitis/ Rhinoconjunctivitis; Mild to moderate asthma; Allergy; Immunotherapy; Mite; Pollen; Vaccine

Outcome Measures

Primary Outcomes (1)

• CSMS: Combined Symptoms and Medication Score

  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. \- The endpoint for each asthma and rhinitis / rhinoconjunctivitis symptom will be as follows: 0 = No symptoms; 1 = Mild; 2 = Moderate; 3 = Severe Total daily symptom score = 0-3 * The asthma medication will be scored based on the therapeutic step in which drugs are included in the GEMA 5 guide. * The rhinitis / rhinoconjunctivitis medication score: 0 = No medication; 1 = oral or topical (eyes or nose) non-sedative H1 antihistamines (H1A); 2 = intranasal corticosteroids (INS) with / without H1A; 3 = oral corticosteroids with/without (INS), with/without H1A Total daily medication score = 0-3

  12 months

Secondary Outcomes (14)

• Medication-free days

  12 months

• Symptom-free days

  12 months

• Respiratory function_FEV1

  12 months

• Respiratory function_PEF

  12 months

• Asthmatic exacerbations

  12 months

Study Arms (4)

MM09-MG01(30.000-30.000)

EXPERIMENTAL

30,000 AU/mL of MM09 and 30,000 AU/mL of MG01 of subcutaneous immunotherapy once a month for 11 months

Biological: MM09-MG01(30.000-30.000)

MG01(30.000)

EXPERIMENTAL

30,000 AU/mL of MG01 of subcutaneous immunotherapy once a month for 11 months

Biological: MG01(30.000)

MM09(30.000)

EXPERIMENTAL

30,000 AU/mL of MM09 of subcutaneous immunotherapy once a month for 11 months

Biological: MM09(30.000)

Placebo subcutaneous

PLACEBO COMPARATOR

The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.

Biological: Placebo subcutaneous

Interventions

MM09-MG01(30.000-30.000) BIOLOGICAL

Mite mixture (Dermatophagoides pteronyssinus and Dermatophagoides farinae) with a concentration of 30,000 AU / mL and grasses mixture (Phleum pratense, Holcus lanatus, Poa pratensis, Festuca elatior, Lolium perenne and Dactylis glomerata) with a concentration of 30,000 AU / mL: Purified allergenic extract, adsorbed in aluminum hydroxide and polymerized with glutaraldehyde

MM09-MG01(30.000-30.000)

MG01(30.000) BIOLOGICAL

Grasses mixture (Phleum pratense, Holcus lanatus, Poa pratensis, Festuca elatior, Lolium perenne and Dactylis glomerata) with a concentration of 30,000 AU / mL: Purified allergenic extract, adsorbed in aluminum hydroxide and polymerized with glutaraldehyde

MG01(30.000)

MM09(30.000) BIOLOGICAL

Mite mixture (Dermatophagoides pteronyssinus and Dermatophagoides farinae) with a concentration of 30,000 AU / mL: Purified allergenic extract, adsorbed in aluminum hydroxide and polymerized with glutaraldehyde

MM09(30.000)

Placebo subcutaneous BIOLOGICAL

The same solution, presentation, method of administration, frequency, and duration as the active treatment, but without active ingredients.

Placebo subcutaneous

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who have signed the informed consent
• 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.
• 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.
• 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.
• 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:
• 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).
• 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.
• 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.
• Subjects with a negative prick test for fungi. If the specific IgE determination has been made, the result shall be \< 0,35 KU/L.
• 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.
• Subjects aged between 12 and 65 years, inclusive.
• Subjects capable of complying with the dosing regimen.
• Women of childbearing age (from menarche) should submit a urine pregnancy test with a negative result at the time of enrolment in the trial.
• 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.
• Subjects who have a smartphone to record symptoms and medication.

You may not qualify if:

• Subjects who have received prior immunotherapy treatment in the preceding 5 years for any aeroallergen.
• 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.
• Subjects who have previously presented a serious secondary reaction during the performance of diagnostic skin tests using the prick test.
• Subjects under treatment with ß-blockers.
• Subjects under treatment with immunosuppressive or biological drugs.
• Subjects with chronic urticaria in the past 2 years, severe anaphylaxis, or a history of hereditary angioedema.
• Subjects who have any pathology in which the administration of adrenaline is contraindicated (hyperthyroidism, HT, heart disease, etc.).
• 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.
• Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumour diseases or with a diagnosis of immunodeficiencies.
• Subject whose condition prevents him / her from offering cooperation and or who resents severe psychiatric disorders, according to investigator criteria.
• Subjects with known allergies to other investigational product components other than grass pollen or mites.
• Subjects with diseases of the lower respiratory tract other than asthma such as emphysema or bronchiectasis.
• Pregnant or lactating women.

Sponsors & Collaborators

• Inmunotek S.L.: lead
• BioClever 2005 S.L.: collaborator
• NTS hub S.L: collaborator

Study Sites (13)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Santa Bárbara

Puertollano, Ciudad Real, 13500, Spain

Location

Hospital el Bierzo

Ponferrada, León, 24404, Spain

Location

Hospital Universitario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario A Coruña

A Coruña, 15006, Spain

Location

Centro Médico ASISA Dr. Lobatón

Cadiz, 11008, Spain

Location

C.P.E. Virgen de la Cinta - Hospital Universitario Juan Ramón Jiménez

Huelva, 21003, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Quirón Salud Málaga

Málaga, 29004, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario de Álava

Vitoria-Gasteiz, Álava, 01009, Spain

Location

Related Publications (3)

• 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.

  PMID: 18445082 BACKGROUND

• 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.

  PMID: 25130503 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Rhinitis, Allergic, Perennial; Dust Mite Allergy; Rhinitis, Allergic, Seasonal; Hypersensitivity

Condition Hierarchy (Ancestors)

Rhinitis, Allergic; Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Immune System Diseases

Study Officials

• Ana Isabel Tabar Purroy, MD; PhD

  Complejo Hospitalario de Navarra

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the trial, both the investigator and the included subjects will be unaware of the treatment each subject is receiving. The person in charge of data analysis will also not know the treatment assigned to each subject until the database has been closed. So that neither the subject nor the investigator knows what treatment each subject is receiving, all the trial medication is identical in terms of outer packaging and appearance.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, placebo-controlled, multi-center trial

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: May 6, 2021
• Study Start: April 30, 2021
• Primary Completion: October 9, 2023
• Study Completion: October 9, 2023
• Last Updated: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (13)