The Effect of Allergen Immunotherapy on Anti-viral Immunity in Patients With Allergic Asthma

NCT04100902 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: VITAL
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Aim: To investigate the possible immune modulatory effects of allergen immunotherapy (AIT) on respiratory immunity in patients with allergic asthma (AA). Background: Allergic sensitization to aeroallergens is a common co-morbidity in asthma that is associated with more frequent and severe asthma attacks. The investigators have recently shown that patients with allergic asthma also have an increased risk of pneumonia, and hence allergy in asthma may be associated with a relative respiratory immunodeficiency. However, the increased risk was obliterated in patients treated with AIT. Methods: Patients with asthma sensitized to house-dust mite (HDM) is enrolled in a randomized, double-blind, placebo-controlled study of HDM-AIT. Patients will be scheduled for 9 visits through 8 months including, randomization to 6 months of treatment with either HDM-AIT (Acarizax/Odactra) or placebo. Primary interferons (IFN) type I and III will be investigated in human bronchial epithelial cells as the primary outcome. Secondary outcomes such as: Inflammatory cytokines, immunologic phenotype and immunohistochemistry will be investigated in bronchial biopsies, blood, bronchoalveolar lavage fluid, sputum and HDM-patch biopsies as well as a thorough respiratory and allergic evaluation. Expected outcomes: The investigators expect that, patients with AA have 1) decreased production of anti-viral type I and III IFN and that AIT increases these measures. 2) Anti-bacterial response is reduced through IL12, ß-defensin and IFN-γ and that AIT increases these measures. 3) Lastly, the investigators expect that T-cell response is dysregulated (Th1↓1/Th2↑) in patients with AA and that these findings are modulated in an immuno-protective direction after AIT. Perspectives: This project will expand our understanding of the clinical significance of allergy in asthma in a completely novel direction and show how AIT may modulate the immune response to prevent infections.

Conditions

Allergic Asthma Due to Dermatophagoides Pteronyssinus

Keywords

Allergic asthma; Allergen Immunotherapy; Anti-viral immunity; House dust mite

Outcome Measures

Primary Outcomes (3)

• ΔIFN-ß gene and/or protein expression

  To investigate the potential change in viral induced interferon response in HBECs from V3, V12, after 24 weeks of HDM-SLIT therapy or placebo, after stimulation with a combination of: HDM-allergen +/- viral infection mimics (RV16 or Poly(I:C))

  Baseline and 24 weeks

• ΔIFN-λ gene and/or protein expression

  To investigate the potential change in viral induced interferon response in HBECs from V3, V12, after 24 weeks of HDM-SLIT therapy or placebo, after stimulation with a combination of: HDM-allergen +/- viral infection mimics (RV16 or Poly(I:C))

  Baseline and 24 weeks

• ΔViral load

  To investigate the potential change in viral load in HBECS from from V3, V12, after 24 weeks of HDM-SLIT therapy or placebo, after stimulation with a combination of HDM-allergen +/- viral infection mimics (RV16 or Poly(I:C))

  Baseline and 24 weeks

Secondary Outcomes (15)

• ΔIFN-ß gene and/or protein expression in viral/bacterial co-stimulation assay

  Baseline and 24 weeks

• ΔIFN-λ gene and/or protein expression in viral/bacterial co-stimulation assay

  Baseline and 24 weeks

• ΔIL-12

  Baseline and 24 weeks

• Δß-defensin

  Baseline and 24 weeks

• ΔIFN-γ

  Baseline and 24 weeks

Study Arms (2)

Odactra 12-sq HDM sublingual tablet

ACTIVE COMPARATOR

House Dust Mite, sublingual tablet

Drug: ODACTRA 12 SQ-HDM Sublingual Tablet

Placebo sublingual tablet

PLACEBO COMPARATOR

Placebo, sublingual tablet

Drug: Placebo sublingual tablet

Interventions

ODACTRA 12 SQ-HDM Sublingual Tablet DRUG

Subjects are randomized to either HDM-AIT or Placebo for 24 weeks of therapy

Also known as: 12-SQ-HDM sublingual tablet

Odactra 12-sq HDM sublingual tablet

Placebo sublingual tablet DRUG

Subjects are randomized to either HDM-AIT or Placebo for 24 weeks of therapy

Placebo sublingual tablet

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Age ≥18 through ≤ 65, inclusive at the time of V1
• A historic verified diagnosis of asthma as defined by 1 positive of following tests:
• Reversibility to Beta-2-agonist
• Positive mannitol challenge test
• Positive methacholine test
• Positive peak-flow variation test
• Positive eucapnic voluntary hyperventilation test
• Exercise test
• Mild to severe symptoms of of HDM induced rhinitis for at least one year (acc. ARIA 2008 Bousqet et al. 2008).
• ≥1 self-reported worsening of asthma symptoms in relations to viral infection within last 12 months
• \. A postbronchodilator FEV1 value of ≥ 70% at V1
• \. ACQ-6 ≥ 1 at V1
• \. A stable asthma controller regimen with ICS for at least 4 weeks prior to V1 (GINA 2-4)
• \. Daily dose of ICS at V1 (budesonide equivalent) ≥400µg 11. Sensitisation to HDM defined by one of the following:

You may not qualify if:

• Any of the following would exclude the subject from participation in the study:
• Oral corticosteroids (any dose for more than 3 days) 8 weeks prior to V1 and during run-in.
• Acute upper or lower respiratory infections requiring antibiotics or antiviral medications 6 weeks prior to V1 and during run-in.
• Severe oral conditions such as but not limited to:
• Oral ulcers
• Oral lichen planus
• Oral mycosis
• Smoking any kind
• Quit \> 6 months prior to V1.
• ≥ 10 pack years
• Positive skin prick test defined as a wheel diameter ≥ 3 mm:
• a. Alternaria, Cladosporium, Aspergillus
• Positive skin prick test defined as a wheel diameter ≥ 3 mm for- and with anamnestic relevant exposure to:
• a. Cat, Dog, Horse
• Ever in treatment with any AIT

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• University of Copenhagen: collaborator
• ALK-Abelló A/S: collaborator
• Lund University: collaborator

Study Sites (1)

Respiratory Research Unit

Copenhagen, 2400, Denmark

Location

Related Publications (1)

• Woehlk C, Ramu S, Sverrild A, Nieto-Fontarigo JJ, Vazquez-Mera S, Cerps S, Pulga A, Andreasson LM, Eriksen LL, Dyhre-Petersen N, Menzel M, Klein DK, Hansen S, Uller L, Porsbjerg C. Allergen Immunotherapy Enhances Airway Epithelial Antiviral Immunity in Patients with Allergic Asthma (VITAL Study): A Double-Blind Randomized Controlled Trial. Am J Respir Crit Care Med. 2023 May 1;207(9):1161-1170. doi: 10.1164/rccm.202209-1708OC.

  PMID: 36701676 DERIVED

Study Officials

• Celeste Porsbjerg, Professor

  Respiratory Research Unit, department of Respiratory Medicine, Bispebjerg University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 23, 2019
• First Posted: September 24, 2019
• Study Start: January 20, 2020
• Primary Completion: February 27, 2022
• Study Completion: February 27, 2022
• Last Updated: May 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)