For study teams

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Background

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Trial Design

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Inclusion & Exclusion Criteria

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Frequently Asked Questions

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Contact Details

Background

The emergence of asthma and allergic disorders as a generational epidemic over the last 30 years has had a major health and socio-economic impact and thus represents a major challenge worldwide. Preventing asthma should be the highest priority, given that it is the most common chronic disease of childhood and the prevalence continues to increase.

Allergen Immunotherapy (AIT) modulates the basic immunologic mechanism of the allergic disease and potentially has long-term, durable efficacy and disease-modifying effects. Repeated administration of high allergen loads has the potential to overcome sensitisation and drive the immune system into a tolerogenic state.

House dust mite (HDM) allergen sensitisation is the most important risk factor for the development of asthma in children. We postulate that treatment of at-risk children with high doses of HDM will enhance the development of specific tolerance against this allergen, as well as having additional benefits beyond this allergen specific effect.

Our current project is intended to provide definitive proof of efficacy that asthma can be prevented. We propose to use HDM allergen as a monotherapy for primary prevention on the basis that there is very little evidence that AIT to multiple allergen mixture is effective in the treatment of asthma.

Trial design

PAPA is a randomised (1:1), double blinded, placebo controlled, parallel arms, multi-site trial. The PAPA trial aims to investigate whether prophylactic house dust mite sublingual allergen immunotherapy can prevent childhood asthma.

Children will be in one of two groups:

  • Acarizax® HDM-SLIT tablet (12SQ) once daily for 3 years
  • Placebo (identical) tablet once daily for 3 years

We will then compare the two groups to establish the efficacy and safety of house dust mite sublingual Immunotherapy (HDM-SLIT) by comparing Acarizax® and placebo, when given sublingually for 3 years to high-risk infants aged between 6 to 12 months at enrolment in preventing the development of atopic recurrent wheeze (suurogate endpoint for the development of asthma).

The trial aims to recruit 434 from approximately 12 sites across the UK.

Inclusion criteria

  • Parent/guardian must be able to understand and provide informed consent.
  • Aged 5 to 12 months of age at randomisation.
  • High risk of asthma (two or more of the three criteria);
    • Single OR dual heredity for allergy (at least one biological mother, father or sibling affected by asthma or allergy, assessed through standardised questionnaires).
    • Atopic dermatitis.
    • Allergen sensitization
Mother holding her baby to her chest while female doctor examining him with stethoscope at hospital

Exclusion criteria

  • Evidence of sensitisation to HDM on skin prick test (SPT) ≥3 mm wheal diameter OR sIgE > 0.35 kU/L.
  • Prematurity (<37 weeks).
  • Faltering growth and/or need for oxygen for more than 5 days in the neonatal period or history of intubation or mechanical ventilation.
  • Other significant medical conditions including but not limited to eosinophilic esophagitis, seizures, major congenital anomalies, cardiac disorders requiring medical therapy, cystic fibrosis, chronic pulmonary diseases, bronchopulmonary dysplasia, significant developmental delay, cerebral palsy, immunodeficiency (primary or secondary).
  • Use of investigational drugs since birth
  • Expecting to relocate out of area within 4 years of study initiation
  • Deemed as unable to adhere to study activities by the investigator
  • Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant’s ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
  • Has any clinically significant abnormal vital sign or laboratory value that in the opinion of the investigator would preclude participation in the trial.

Frequently asked questions

Please see our frequently asked questions guidance sheet.

Further support

If you have any questions about the trial, you can contact the PAPA trial team at the Imperial Clinical Trials Unit by emailing papatrial@imperial.ac.uk or emailing the Chief Investigator Professor Syed Hasan Arshad at S.H.Arshad@soton.ac.uk