UNC Cashew Sublingual Immunotherapy

Official title

Cashew Allergy Study in Children: Assessing Desensitization, Efficacy, and Safety (CASCADES Study)

Overview

The CASCADES study will investigate the safety and efficacy of sublingual immunotherapy (SLIT) for the treatment of cashew allergy in children ages 1-11 years old. Primary efficacy will be assessed after 18 months of cashew SLIT. Lab studies and an oral food challenge after 6 months of cashew SLIT will help determine how quickly cashew SLIT begins to take effect.

Detailed description

The CASCADES study is an 18-month randomized, placebo-controlled trial of cashew sublingual immunotherapy (CASHEW SLIT) in children 1-11 years of age with cashew allergy . Children ages 1-11 years with double-blind placebo-controlled food challenge (DBPCFC) proven allergy to cashew randomized 2:1 to active cashew SLIT or placebo. Participants will undergo a 5-month dose buildup period followed by a DBPCFC at month 6. Participants will then complete an additional 12 months of maintenance cashew SLIT or placebo followed by a DBPCFC at month 18. Safety will be assessed throughout the study. Skin prick testing (SPT), blood sampling, and saliva collection will be performed at baseline and at months 1, 3, 6, 12, and 18 to evaluate for immune biomarker changes.

Interventions

• Drug Cashew sublingual immunotherapy
  Glycerinated cashew extract for use in sublingual immunotherapy
• Drug Placebo sublingual immunotherapy
  Glycerinated saline for placebo sublingual immunotherapy

Primary outcome measures

• Desensitization to cashew at month 18 [Time frame: 18 months]

Secondary outcome measures (7)

• Full desensitization to cashew at month 18 [Time frame: 18 months]
• Desensitization to cashew at month 6 [Time frame: 6 months]
• Adverse events related to study drug dosing [Time frame: 18 months]
• Change in cashew skin prick testing [Time frame: Baseline, Months 6 and 18]
• Change in cashew Immunoglobulin E (IgE) [Time frame: Baseline, Months 6 and 18]
• Change in cashew Immunoglobulin G4 (IgG4) [Time frame: Baseline, Months 6 and 18]
• Change in Cashew-Specific IgG4/IgE Ratio [Time frame: Baseline, Months 6 and 18]

Eligibility criteria

Inclusion criteria

• Age 1-11 years at enrollment
• Cashew allergy, with allergy defined as:
• History of clinical reaction to cashew AND cashew-specific IgE >/=0.35 kUA/L AND cashew SPT >/=3 mm
• OR if no prior reaction, cashew-specific IgE >/=5 kUA/L AND cashew SPT >/=3 mm
• Positive Double-Blind Placebo Controlled Food Challenge (DBCPFC) to 443 mg cumulative cashew at enrollment
• If female of child-bearing potential, must have a negative urine or serum pregnancy test
• If female of childbearing potential (defined as females who have reached menarche or who are 12 years or older), must agree to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods (barrier methods or oral, injected, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy) during the treatment period

Exclusion criteria

• Inability or unwillingness of a participant and/or parent/legal guardian to give written informed consent and/or assent or comply with the study protocol
• History of severe anaphylaxis to cashew defined as neurological compromise or requiring intubation/mechanical ventilation
• Known oat, wheat, or glycerin allergy
• Poorly controlled or severe asthma/wheezing at screening, defined by at least one of the following criteria:
• Global Initiative for Asthma (GINA) 2024 criteria for uncontrolled asthma
• History of 2 or more systemic corticosteroid courses within 6 months of screening or one course of systemic corticosteroids within 3 months of screening to treat asthma/wheezing
• Prior intubation/mechanical ventilation for asthma/wheezing
• Hospitalization or overnight Emergency Department (ED) visit for asthma/wheezing within 6 months of screening
• Forced expiratory volume in one second (FEV1) <80% of predicted or FEV1/forced vital capacity (FVC) <75%, with or without controller medications (for participants >/= 6 years and older, able to perform spirometry)
• Peak expiratory flow rate (PEFR) <80% of predicted for participants >6 and able to perform peak flow
• Inhaled corticosteroid (ICS) dosing of >500 mcg daily fluticasone (or equivalent ICS)
• Eosinophilic or other inflammatory (e.g., celiac) gastrointestinal disease
• Inability to discontinue antihistamines at least 5 half-lives before scheduled SPT and DBPCFC
• Food immunotherapy such as Oral Immunotherapy (OIT), Sublingual Immunotherapy (SLIT), or Epicutaneous (EPIT) for cashew or pistachio within 6 months of enrollment
• Monoclonal antibodies such as omalizumab (Xolair), dupilumab (Dupixent), benralizumab (Fasenra), mepolizumab (Nucala), or other immunomodulatory therapy within 6 months of enrollment
• Currently on dose escalation of environmental allergen immunotherapy (SCIT or SLIT). Individuals on maintenance allergen immunotherapy can be enrolled
• Participation in any interventional study within the past 3 months
• Pregnant or breastfeeding
• Past or current medical condition or clinical significant laboratory abnormality that, in the opinion of the PI, would make the participant unsafe or otherwise unsuitable for participation in the clinical trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of North Carolina — Chapel Hill

Identifiers

NCT: NCT07170540 · 24-2373 · G-202401-00621

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗