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Walnut Oral Immunotherapy for Tree Nut Allergy (WOIT)

Primary Purpose

Tree Nut Allergy

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Walnut Protein Powder

Oat Powder (placebo)

Open-label Walnut Protein Powder

About this trial

This is an interventional treatment trial for Tree Nut Allergy focused on measuring Walnut allergy, Tree nut allergy, Oral immunotherapy, Food allergy, Desensitization, Sustained unresponsiveness

Eligibility Criteria

6 Years - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Arkansas Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Other

Arm Label

Walnut Protein Powder

Oat Powder

Open-label Walnut Protein Powder

Arm Description

38 weeks on active walnut powder on blinded treatment phase

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Determine in tree nut allergic subjects the effectiveness of walnut oral immunotherapy on clinical desensitization to walnut 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 walnut at approximately 38 weeks on therapy.

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

The percentage of subjects reaching a cumulative protein dose of 2000mg at the desensitization oral food challenge to walnut at week 38

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

Comparison of the number and percentage of subjects in each treatment arm reaching a cumulative protein dose of 2000mg at the week 38 (desensitization) oral food challenge to test tree nut

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

The percentage of subjects demonstrating sustained unresponsiveness to walnut and to the test tree nut by end of study. Analysis group combines both active and placebo-crossover participants during open-label extension arm through the end of study at week 298. Subjects were able to exit the study at assessment timepoints earlier than week 298 if they are able to pass the sustained unresponsiveness oral food challenge, thus the analysis included all subjects through week 298..

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

Evaluation of walnut OIT on the mast cell responses as measured through change in skin prick testing to walnut in participants who were treated with walnut OIT to week 142. Analysis group combines both active and placebo-crossover participants from baseline through open-label treatment phase until the end of study.

Serious Adverse Events Related to Walnut OIT Treatment

Incidence of treatment-related serious adverse events during the study

Full Information

NCT ID

NCT01546753

First Posted

March 1, 2012

Last Updated

April 19, 2023

Sponsor

University of Arkansas

1. Study Identification

Unique Protocol Identification Number

NCT01546753

Brief Title

Walnut Oral Immunotherapy for Tree Nut Allergy

Acronym

WOIT

Official Title

Walnut Oral Immunotherapy for Tree Nut Allergy

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Completed

Study Start Date

April 27, 2012 (Actual)

Primary Completion Date

July 2, 2015 (Actual)

Study Completion Date

July 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Arkansas

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tree Nut Allergy

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

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

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Walnut Protein Powder

Arm Type

Experimental

Arm Description

38 weeks on active walnut powder on blinded treatment phase

Arm Title

Oat Powder

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Open-label Walnut Protein Powder

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Walnut Protein Powder

Other Intervention Name(s)

WOIT

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Oat Powder (placebo)

Other Intervention Name(s)

Oat flour

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Open-label Walnut Protein Powder

Other Intervention Name(s)

Open-label treatment

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

38 weeks of therapy

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

38 weeks

Title

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

Description

The percentage of subjects reaching a cumulative protein dose of 2000mg at the desensitization oral food challenge to walnut at week 38

Time Frame

38 weeks

Title

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

Description

Comparison of the number and percentage of subjects in each treatment arm reaching a cumulative protein dose of 2000mg at the week 38 (desensitization) oral food challenge to test tree nut

Time Frame

38 weeks

Title

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

Description

Time Frame

up to 298 weeks on active treatment

Title

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

Description

Time Frame

142 weeks

Title

Serious Adverse Events Related to Walnut OIT Treatment

Description

Incidence of treatment-related serious adverse events during the study

Time Frame

298 weeks active treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stacie M Jones, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Arkansas Children's Hospital

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72202

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19577283

Citation

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.

Results Reference

background

PubMed Identifier

19477496

Citation

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.

Results Reference

background

PubMed Identifier

21093029

Citation

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.

Results Reference

background

PubMed Identifier

21377034

Citation

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.

Results Reference

background

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Walnut Oral Immunotherapy for Tree Nut Allergy

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