Walnut Oral Immunotherapy for Tree Nut Allergy
Condition: Tree Nut Allergy
MeSH terms: Hypersensitivity; Nut Hypersensitivity
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to determine if walnut oral immunotherapy can be used in
      participants allergic to tree nuts to reduce tree nut allergy and induce changes in the
      participant's immune system.
    

Detailed description: 
      Randomized, placebo controlled, Phase 1-2 study conducted at Arkansas Children's Hospital
      Research Institute (ACHRI) in tree nut allergic participants, ages 6-45 years with
      randomization following a 2:1 (active:placebo) format. The overall objectives were to
      evaluate the efficacy of walnut oral immunotherapy (WOIT) for induction of desensitization to
      walnut (secondary outcome) and a test tree nut (primary outcome) when compared to placebo
      after 38 weeks of treatment as assessed by double-blind, placebo-controlled food challenges
      (DBPCFC) to walnut and a test tree nut in tree nut allergic participants (defined by allergic
      reaction to </= 2 grams of walnut and test tree nut proteins during DBPCFC at study entry).
      Placebo participants were crossed-over to active therapy after unblinding at week 38.
      Participants were followed long-term (up to 6 years) on open-label WOIT treatment and
      assessed at yearly intervals based on pre-specified criteria for clinical outcomes of
      desensitization to walnut and a test tree nut (defined as safely consuming 5 grams of walnut
      and test tree nut protein during DBPCFC while on daily WOIT) and sustained unresponsiveness
      to walnut and a test tree nut (defined as safely consuming 5 grams of walnut and test tree
      nut protein during DBPCFC and 10 grams during an open feeding while off therapy for 4-6
      weeks). Secondary outcomes were evaluated including safety and immune mechanistic parameters.
    

Intervention name(s): Walnut Protein Powder; Oat Powder (placebo); Open-label Walnut Protein Powder
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Blinded study product dosing begins with a 1-day oral desensitization protocol to walnut for subjects in the active arm. Starting at 0.1 mg protein and increasing to a maximum of 6 mg or until allergic symptoms develop. Subjects continue daily dosing of blinded OIT (walnut) with build-up every 2 weeks to a maximum daily dose of 1500mg at week 34, followed by 4 weeks of daily maintenance dosing. OFC to walnut and second tree nut occurs at week 38 then treatment is unblinded and open-label maintenance dosing occurs.; Blinded study product dosing begins with a one-day oral desensitization protocol with placebo (oat) powder. Subjects in the placebo group will undergo the same protocol as those in the active group with placebo OIT dosing. Unblinding to treatment assignment will occur after the 38 week oral food challenge. Placebo subjects will cross-over to active, open-label treatment with walnut powder after the 38 week oral food challenge. beginning with initial escalation day, through build-up and maintenance dosing per the same protocol sequence as noted for active, walnut powder. Subjects will complete an oral food challenge to walnut and the second tree nut at week 38 then will continue on long-term, open-label maintenance dosing until the end of study using same protocol design.; Open-label treatment phase begins after the 38 week oral food challenge with unblinding of treatment assignment. For those on active treatment, daily maintenance dosing occurs for up to a total of 298 weeks. For those on placebo treatment, cross-over to active, open-label treatment occurs using the same active treatment protocol. Placebo-crossover subjects will complete an oral food challenge to walnut and the second tree nut at week 38 of active therapy then continue on long-term, open-label maintenance dosing until the end of study using same protocol design. All subjects may reach a qualifying IgE to walnut/second tree nut early and will undergo an OFCs on and 4 weeks off OIT. All subjects will have OFCs on and 4 weeks off OIT at week 142 and at week 298, unless both walnut/second tree nut OFCs are passed at previous OFC prompting addition of these foods into the diet.
Other intervention name(s): WOIT; Oat flour; Open-label treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Subjects will be randomized in a 2:1 ratio to either active treatment (final dose 1500mg walnut protein (WP), n=20) or placebo (n=10). Subjects will do a 1-day desensitization to enable subjects to tolerate 6 mg of WP or placebo (initial day escalation). After the initial escalation day obtaining at least 1.5mg and up to 6mg of WP or placebo, dosing build-up will be every 2 wks thru dose 24 (34 wks). A maintenance dose will be given for 4 wks, then a 5g protein OFC to walnut & a 5g protein OFC to a 2nd tree nut (~38 wks), then the study will be unblinded. Placebo subjects that fail the OFC will cross-over to active treatment and escalate to 1500mg target dose. Subjects will be followed for 298 wks (~6 yrs) total on active treatment including an OFC (both on & off therapy) to walnut and 2nd tree nut at 142 wk & end of study. Subjects with reduced serum specific IgE to <5kU/L to walnut and 2nd tree nut at yearly visits before the end of study at 298 wks are eligible for a tolerance OFC.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Walnut allergy; Tree nut allergy; Oral immunotherapy; Food allergy; Desensitization; Sustained unresponsiveness