Walnut Oral Immunotherapy for Tree Nut Allergy

NCT01546753 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 113364FARE
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tree Nut Allergy

Keywords

Walnut allergy; Tree nut allergy; Oral immunotherapy; Food allergy; Desensitization; Sustained unresponsiveness

Outcome Measures

Primary Outcomes (1)

• Effectiveness of Walnut OIT on Clinical Desensitization to Test Tree Nut as Measured by Change in Cumulative Tolerated Dose From Baseline to Week 38 at Oral Food Challenge

  Determine in tree nut allergic subjects the effectiveness of walnut oral immunotherapy on clinical desensitization to a second tree nut ("test tree nut") causing allergy when compared to placebo treatment, as measured by the change in cumulative dose from baseline oral food challenge (OFC) to the OFC to the test tree nut at approximately 38 weeks on therapy.

  38 weeks of therapy

Secondary Outcomes (6)

• Evaluation of Desensitization to Walnut Protein as Measured by Change in Cumulative Tolerated Dose From Baseline to Week 38 Oral Food Challenge

  38 weeks

• Number (Percentage) of Subjects Reaching a Cumulative Tolerated Dose of 2000mg Walnut Protein at Desensitization OFC at Week 38

  38 weeks

• Number (Percentage) of Subjects Reaching a Cumulative Tolerated Dose of 2000mg Test Tree Nut Protein at Desensitization OFC at Week 38

  38 weeks

• Number (Percentage) of Subjects Attaining Sustained Unresponsiveness to Walnut and Test Tree Nut Proteins at Week 298 Oral Food Challenge

  up to 298 weeks on active treatment

• Change in Skin Prick Test Wheal Size From Baseline to Week 142 in Active and Placebo Cross-over Subjects Receiving Active Walnut OIT

  142 weeks

Study Arms (3)

Walnut Protein Powder

EXPERIMENTAL

38 weeks on active walnut powder on blinded treatment phase

Drug: Walnut Protein Powder

Oat Powder

PLACEBO COMPARATOR

38 weeks on placebo (oat) powder during blinded treatment phase

Drug: Oat Powder (placebo)

Open-label Walnut Protein Powder

OTHER

Open-label treatment with walnut protein powder up to week 298 of total treatment

Drug: Open-label Walnut Protein Powder

Interventions

Walnut Protein Powder DRUG

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.

Also known as: WOIT

Walnut Protein Powder

Oat Powder (placebo) DRUG

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.

Also known as: Oat flour

Oat Powder

Open-label Walnut Protein Powder DRUG

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.

Also known as: Open-label treatment

Open-label Walnut Protein Powder

Eligibility Criteria

• Age: 6 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 6 to 45 years, either sex, any race, any ethnicity with a convincing clinical history of walnut or another tree nut allergy and either a positive prick skin test (≥ 3mm) or serologic evidence of allergic sensitization (defined as specific IgE \> 0.35 kU/L) to walnut and at least one other tree nut.
• A positive 2000 mg oral food challenge at enrollment to walnut and to one other tree nut.
• Written informed consent from participant and/or parent/guardian
• Written assent from all subjects as appropriate
• All females of child bearing age must be using appropriate birth control

You may not qualify if:

• History of severe anaphylaxis to walnut or other tree nuts, defined as symptoms associated with hypoxia, hypotension or neurologic compromise (cyanosis or SpO2 \< 92% at any stage, hypotension, confusion, collapse, loss of consciousness; or incontinence).
• Known allergy to oat
• Chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy or other respiratory or medical conditions deemed by the investigator to put the subject at increased risk of anaphylaxis or poor outcomes from receiving OIT or undergoing food challenge.
• Poor control or persistent activation of atopic dermatitis
• Active eosinophilic or other inflammatory (e.g., celiac) gastrointestinal disease in the past 2 years.
• Participation in any interventional study for food allergy in the past 6 months
• Participant is on "build-up phase" of immunotherapy (i.e., has not reached maintenance dosing).
• Severe asthma (2007 NHLBI Criteria Steps 5 or 6, see Appendix 2) or poorly controlled mild or moderate asthma
• Inability to discontinue antihistamines for initial day escalation, skin testing or OFC
• Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids) or biologic therapy within the past year
• Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers
• Pregnancy or lactation

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (1)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Related Publications (4)

• Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, Shreffler WG, Steele P, Henry KA, Adair M, Francis JM, Durham S, Vickery BP, Zhong X, Burks AW. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009 Aug;124(2):292-300, 300.e1-97. doi: 10.1016/j.jaci.2009.05.022. Epub 2009 Jul 3.

  PMID: 19577283 BACKGROUND

• Hofmann AM, Scurlock AM, Jones SM, Palmer KP, Lokhnygina Y, Steele PH, Kamilaris J, Burks AW. Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol. 2009 Aug;124(2):286-91, 291.e1-6. doi: 10.1016/j.jaci.2009.03.045. Epub 2009 May 27.

  PMID: 19477496 BACKGROUND

• Kulis M, Li Y, Lane H, Pons L, Burks W. Single-tree nut immunotherapy attenuates allergic reactions in mice with hypersensitivity to multiple tree nuts. J Allergy Clin Immunol. 2011 Jan;127(1):81-8. doi: 10.1016/j.jaci.2010.09.014. Epub 2010 Nov 18.

  PMID: 21093029 BACKGROUND

• Varshney P, Jones SM, Scurlock AM, Perry TT, Kemper A, Steele P, Hiegel A, Kamilaris J, Carlisle S, Yue X, Kulis M, Pons L, Vickery B, Burks AW. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011 Mar;127(3):654-60. doi: 10.1016/j.jaci.2010.12.1111.

  PMID: 21377034 BACKGROUND

MeSH Terms

Conditions

Nut Hypersensitivity; Food Hypersensitivity

Condition Hierarchy (Ancestors)

Nut and Peanut Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Limitations and Caveats

Small sample size High screen failure rate High level of oropharyngeal symptoms Anxiety resulting in early termination Dosing fatigue with daily dosing Requirement for multiple food challenges in multi-tree nut assessment

Results Point of Contact

• Title: Dr. Stacie Jones
• Organization: University of Arkansas for Medical Sciences

JonesStacieM@uams.edu

(501) 364-1060

Study Officials

• Stacie M Jones, MD

  University of Arkansas for Medical Sciences / Arkansas Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 1, 2012
• First Posted: March 7, 2012
• Study Start: April 27, 2012
• Primary Completion: July 2, 2015
• Study Completion: July 2, 2020
• Last Updated: May 12, 2023
• Results First Posted: May 12, 2023

Record last verified: 2023-04

Locations

US (1)