Allergy;Food, Allergy to Cashew Nut (Disorder), Allergy to Shrimp
Conditions
Keywords
OIT, Oral Immunotherapy, Cashew Allergy, Shrimp Allergy
Brief summary
A prospective Phase 2, single-center, single-allergen OIT of cashew or shrimp in participants with proven allergies to either cashew or shrimp, respectively. We intend to treat 72 participants, ages 7 to 55 years with an allergy to either cashew, or shrimp determined by Double Blind-Placebo Controlled-Food Challenge (DBPCFC), allergy history, clinical symptoms, food-allergen (FA)-specific IgE levels, and skin prick test (SPT).
Detailed description
A prospective Phase 2, single-center, single-allergen OIT of cashew or shrimp in participants with proven allergies to either cashew or shrimp, respectively. We intend to treat 72 participants, ages 7 to 55 years with an allergy to either cashew or shrimp determined by Double Blind-Placebo Controlled-Food Challenge (DBPCFC), allergy history, clinical symptoms, food-allergen (FA)-specific IgE levels, and skin prick test (SPT). Enrolled participants must be positive at or before the 300 mg (443 mg cumulative) dosing level of FA protein. OIT treatment groups will be cashew or shrimp. All cohorts will undergo an updosing regimen starting at 5 mg allergen, with dose escalation every 2 weeks to reach a 1000 mg dose at week 28, after which they will be maintained at that dose for 24 weeks. At the conclusion of the maintenance phase (Week 52), participants will undergo DBPCFC. Participants that pass their food challenge with no or mild objective reactions to up to a cumulative 2043 mg of the FA allergen in their OIT at the end of this phase (primary outcome) will be considered desensitized and have successfully met the primary endpoint. All participants then will continue in the study by undergoing withdrawal from OIT for 6 weeks to examine mechanisms underlying sustained responsiveness (SU) which will be defined as a participant's passing a DBPCFC with no or mild objective reaction to up to a cumulative 2043 mg of the FA allergen in their DBPCFC at week 58. Those participants who pass the Week 58 challenge up to a cumulative of 2043 mg will be given the option to continue the withdrawal phase up to Week 64 which will be end of study. Week 58 will be end of study for those who do not opt for this continuation of withdrawal.
Interventions
DRUGCashew or Shrimp Oral Immunotherapy
All cohorts will undergo an updosing regimen starting at 5 mg allergen, with dose escalation every 2 weeks to reach a 1000 mg dose at week 28, after which they will be maintained at that dose for 24 weeks. At the conclusion of the maintenance phase (Week 52), participants will undergo DBPCFC.
Sponsors
Sayantani B. Sindher
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Food allergy OIT in a single group design
Eligibility
Sex/Gender
ALL
Age
7 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Subject and/or parent guardian must be able to understand and provide informed consent * Age 7 through 55 years (inclusive) * Clinical history of allergy to cashew or shrimp-containing foods * Serum IgE to cashew or shrimp of ≥0.35 kUA/L \[determined by UniCAPTM within the past 12 months\] and/or a SPT to cashew or shrimp ≥3 mm compared to control * Experience dose-limiting symptoms at or before the 300 mg challenge dose of FA protein on Screening DBPCFC conducted in accordance with PRACTALL guidelines * Written informed consent from adult participants * Written informed consent from parent/guardian for minor participants * Written assent from minor participants as appropriate (e.g., above the age of 7 years or the applicable age per local regulatory requirements) * All female subjects of child-bearing potential will be required to provide a blood or urine sample for pregnancy testing that must be negative one week before being allowed to participate in the study. * Use of effective birth control by female participants of child-bearing potential.
Exclusion criteria
* Inability or unwillingness of a participant to give written informed consent or comply with study protocol * History of uncontrolled cardiovascular disease, including uncontrolled hypertension * History of other chronic disease (other than asthma, atopic dermatitis, or allergic rhinitis) requiring therapy (e.g., heart disease, diabetes) that is, or is at significant risk of becoming unstable or requiring a change in chronic therapeutic regimen and, in the opinion of the Principal Investigator, would represent a risk to the subject's health or safety in this study or the subject's ability to comply with the study protocol. * History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD) grade 3 according to CTCAE version 5.0, symptoms of dysphagia (e.g., difficulty swallowing, food "getting stuck"), or recurrent gastrointestinal symptoms of undiagnosed etiology * Current participation in any other interventional study * Subject is currently in the build-up phase of immunotherapy to another allergen and is on maintenance immunotherapy dose for any allergen related to cashew or shrimp * Severe asthma (NAEPP EPR-3 Medication Criteria Steps 5 or 6) * Mild or moderate asthma (NAEPP EPR-3 Medication Criteria Steps 1-4), if not controlled as indicated by an ACT\<19 * A hospitalization for asthma in the past 6 months * ER visit for asthma within the past 6 months * Burst or steroid course for asthma in the past 6 months * Use of omalizumab or biologic therapy (e.g., infliximab, rituximab, etc.) within the past 6 months * Use of complementary and alternative medicine (CAM) treatment modalities (e.g., herbal remedies) for atopic and /or non-atopic disease within 90 days preceding Initial Dose Escalation Day (IDED) or at any time after the IDED * Use of beta-blockers (oral) * Pregnancy or lactation * Allergy to oat * History of severe anaphylaxis to cashew or shrimp with symptoms including hypotension requiring fluid resuscitation and/or the need for mechanical ventilation within the last year * Use of investigational drugs within 12 weeks of participation * Past or current medical problems or findings from physical assessment 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Expression of CD28 in the CD4+ Allergen Specific (CD154+) | baseline and 52 week | Expression of CD28 in the CD4+ allergen specific (CD154+) T-cells at baseline and 52 weeks, reported as the percentage of allergen specific (reactive) cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expression of CD28+ Allergen Specific (CD154+) T-cells | baseline, week 52 and week 58 | Expression of CD28+ allergen specific (CD154+) T-cells at baseline, week 52, and week 58, reported as the percentage of allergen specific (reactive) cells. |
| Expression of the Mechanistic Markers Vis Luminex Assay | baseline, week 52, and week 58 | Expression of the following measures in CD4+CD28+ allergen specific (CD154+) T-cells at baseline, week 52, and week 58. Data were collected for IFN-gamma, IL-4 and IL-10 via Luminex assay. Data collection was planned for receptor diversity in allergen specific T cell CDR3b as compared to non-specific T cells, and TGF beta, but these data were not collected. The median value (with full range) of mean fluorescence intensity across participants is reported for each time point. |
| Expression of the Mechanistic Marker Via Flow Cytometry | baseline, week 52, and week 58 | Expression of the following measures in CD4+CD28+ allergen specific (CD154+) T-cells at baseline, week 52, and week 58. Data were collected for GPR15 via flow cytometry resulting in mean fluorescence intensity. Data collection was planned for receptor diversity in allergen specific T cell CDR3b as compared to non-specific T cells, and TGF beta, but these data were not collected. The median value (with full range) of mean fluorescence intensity across participants is reported for each time point. |
Countries
United States
Contacts
STUDY_DIRECTORSayantani Sindher, MD
Stanford University, SNP Center for Food Allergy and Asthma Research
Participant flow
Recruitment details
Participants with an allergy to Cashew or Shrimp were enrolled. The study was to examine the efficacy of oral immunotherapy regimen overtime, without comparisons between allergen groups.
Pre-assignment details
58 participants consented and assessed for eligibility. 2 participants withdrew consent and 4 participants screen failed, and were not allocated to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cashew Oral Immunotherapy Participants with an allergy to Cashew. | 40 |
| Shrimp Oral Immunotherapy Participants with an allergy to Shrimp. | 12 |
| Total | 52 |
Baseline characteristics
| Characteristic | Cashew Oral Immunotherapy | Shrimp Oral Immunotherapy | Total |
|---|---|---|---|
| Age, Continuous | 14 years | 23.5 years | 14 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 11 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| History of Allergic Rhinitis | 28 Participants | 9 Participants | 37 Participants |
| History of Asthma | 19 Participants | 7 Participants | 26 Participants |
| History of Atopic Dermatitis | 24 Participants | 6 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 4 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 7 Participants | 18 Participants |
| Region of Enrollment United States | 40 Participants | 12 Participants | 52 Participants |
| Sex: Female, Male Female | 19 Participants | 8 Participants | 27 Participants |
| Sex: Female, Male Male | 21 Participants | 4 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 12 |
| other Total, other adverse events | 40 / 40 | 12 / 12 |
| serious Total, serious adverse events | 1 / 40 | 0 / 12 |
Outcome results
Primary
Expression of CD28 in the CD4+ Allergen Specific (CD154+)
Expression of CD28 in the CD4+ allergen specific (CD154+) T-cells at baseline and 52 weeks, reported as the percentage of allergen specific (reactive) cells.
Time frame: baseline and 52 week
Population: participants with baseline and week 52 CD28 expression data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cashew Oral Immunotherapy | Expression of CD28 in the CD4+ Allergen Specific (CD154+) | baseline | 99 percentage of allergen reactive cells |
| Cashew Oral Immunotherapy | Expression of CD28 in the CD4+ Allergen Specific (CD154+) | week 52 | 100 percentage of allergen reactive cells |
| Shrimp Oral Immunotherapy | Expression of CD28 in the CD4+ Allergen Specific (CD154+) | baseline | 98.9 percentage of allergen reactive cells |
| Shrimp Oral Immunotherapy | Expression of CD28 in the CD4+ Allergen Specific (CD154+) | week 52 | 97.7 percentage of allergen reactive cells |
| All Participants | Expression of CD28 in the CD4+ Allergen Specific (CD154+) | baseline | 99 percentage of allergen reactive cells |
| All Participants | Expression of CD28 in the CD4+ Allergen Specific (CD154+) | week 52 | 99.5 percentage of allergen reactive cells |
Comparison: analysis of the change from baseline in CD28 expressionp-value: 0.3Mixed Models Analysis
Secondary
Expression of CD28+ Allergen Specific (CD154+) T-cells
Expression of CD28+ allergen specific (CD154+) T-cells at baseline, week 52, and week 58, reported as the percentage of allergen specific (reactive) cells.
Time frame: baseline, week 52 and week 58
Population: participants with baseline, week 52, or week 58 CD28 expression
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cashew Oral Immunotherapy | Expression of CD28+ Allergen Specific (CD154+) T-cells | week 52 | 100 percentage of allergen reactive cells |
| Cashew Oral Immunotherapy | Expression of CD28+ Allergen Specific (CD154+) T-cells | baseline | 99 percentage of allergen reactive cells |
| Cashew Oral Immunotherapy | Expression of CD28+ Allergen Specific (CD154+) T-cells | week 58 | 100 percentage of allergen reactive cells |
| Shrimp Oral Immunotherapy | Expression of CD28+ Allergen Specific (CD154+) T-cells | week 52 | 97.7 percentage of allergen reactive cells |
| Shrimp Oral Immunotherapy | Expression of CD28+ Allergen Specific (CD154+) T-cells | baseline | 98.9 percentage of allergen reactive cells |
| Shrimp Oral Immunotherapy | Expression of CD28+ Allergen Specific (CD154+) T-cells | week 58 | 99.2 percentage of allergen reactive cells |
| All Participants | Expression of CD28+ Allergen Specific (CD154+) T-cells | baseline | 99 percentage of allergen reactive cells |
| All Participants | Expression of CD28+ Allergen Specific (CD154+) T-cells | week 58 | 100 percentage of allergen reactive cells |
| All Participants | Expression of CD28+ Allergen Specific (CD154+) T-cells | week 52 | 99.5 percentage of allergen reactive cells |
Comparison: within-group analysis of change from baseline to week 52p-value: 0.82Mixed Models Analysis
Comparison: within-group analysis on the change from baseline to week 58p-value: 0.053Mixed Models Analysis
Comparison: within-group analysis of change from week 52 to week 58p-value: 0.062Mixed Models Analysis
Comparison: within-group analysis of change from baseline to week 52p-value: 0.3Mixed Models Analysis
Comparison: within-group analysis of change from baseline to week 58p-value: 0.54Mixed Models Analysis
Comparison: within-group analysis of change from week 52 to week 58p-value: 0.82Mixed Models Analysis
Secondary
Expression of the Mechanistic Markers Vis Luminex Assay
Expression of the following measures in CD4+CD28+ allergen specific (CD154+) T-cells at baseline, week 52, and week 58. Data were collected for IFN-gamma, IL-4 and IL-10 via Luminex assay. Data collection was planned for receptor diversity in allergen specific T cell CDR3b as compared to non-specific T cells, and TGF beta, but these data were not collected. The median value (with full range) of mean fluorescence intensity across participants is reported for each time point.
Time frame: baseline, week 52, and week 58
Population: participants who had baseline, week 52, or week 58 Luminex data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at week 58 | 53 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at week 58 | 37 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at week 58 | 33.5 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at baseline | 33 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at week 52 | 32 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at week 52 | 38.5 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at week 52 | 56 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at baseline | 53 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at baseline | 36.5 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at baseline | 30.2 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at week 52 | 34 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at baseline | 53.8 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at week 52 | 61.2 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at week 58 | 58 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at week 58 | 30 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at baseline | 36.5 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at week 52 | 38.5 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at week 58 | 36.2 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at week 52 | 60 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at baseline | 32 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at baseline | 36.5 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at baseline | 53 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at week 58 | 37 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at week 52 | 33 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IFN-gamma at week 58 | 55 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IL-10 at week 52 | 38.5 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Markers Vis Luminex Assay | IL-4 at week 58 | 32.5 mean fluorescence intensity |
Comparison: within-group analysis of change in INFG from baseline to week 52p-value: 0.25Mixed Models Analysis
Comparison: within-group analysis of change in INFG from baseline to week 58p-value: 0.24Mixed Models Analysis
Comparison: within-group analysis of change in INFG from week 52 to week 58p-value: 0.61Mixed Models Analysis
Comparison: within-group analysis of change in INFG from baseline to week 52p-value: 0.034Mixed Models Analysis
Comparison: within-group analysis of change in INFG from baseline to week 58p-value: 0.45Mixed Models Analysis
Comparison: within-group analysis of change in INFG from week 52 to week 58p-value: 0.12Mixed Models Analysis
Comparison: within-group analysis of change in IL4 from baseline to week 52p-value: 0.83Mixed Models Analysis
Comparison: within-group analysis of change in IL4 from baseline to week 58p-value: 0.67Mixed Models Analysis
Comparison: within-group analysis of change in IL4 from week 52 to week 58p-value: 0.8Mixed Models Analysis
Comparison: within-group analysis of change in IL4 from baseline to week 52p-value: 0.46Mixed Models Analysis
Comparison: within-group analysis of change in IL4 from baseline to week 58p-value: 0.48Mixed Models Analysis
Comparison: within-group analysis of change in IL4 from week 52 to week 58p-value: 0.25Mixed Models Analysis
Comparison: within-group analysis of change in IL10 from baseline to week 52p-value: 0.14Mixed Models Analysis
Comparison: within-group analysis of change in IL10 from baseline to week 58p-value: 0.73Mixed Models Analysis
Comparison: within-group analysis of change in IL10 from week 52 to week 58p-value: 0.16Mixed Models Analysis
Comparison: within-group analysis of change in IL10 from baseline to week 52p-value: 0.47Mixed Models Analysis
Comparison: within-group analysis of change in IL10 from baseline to week 58p-value: 0.84Mixed Models Analysis
Comparison: within-group analysis of change in IL10 from week 52 to week 58p-value: 0.55Mixed Models Analysis
Secondary
Expression of the Mechanistic Marker Via Flow Cytometry
Expression of the following measures in CD4+CD28+ allergen specific (CD154+) T-cells at baseline, week 52, and week 58. Data were collected for GPR15 via flow cytometry resulting in mean fluorescence intensity. Data collection was planned for receptor diversity in allergen specific T cell CDR3b as compared to non-specific T cells, and TGF beta, but these data were not collected. The median value (with full range) of mean fluorescence intensity across participants is reported for each time point.
Time frame: baseline, week 52, and week 58
Population: participants who had baseline, week 52, or week 58 Flow cytometry data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cashew Oral Immunotherapy | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at week 52 | 1778 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at baseline | 1801 mean fluorescence intensity |
| Cashew Oral Immunotherapy | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at week 58 | 1441 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at week 52 | 1922 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at baseline | 1585 mean fluorescence intensity |
| Shrimp Oral Immunotherapy | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at week 58 | 2715 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at baseline | 1664 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at week 58 | 1609 mean fluorescence intensity |
| All Participants | Expression of the Mechanistic Marker Via Flow Cytometry | GPR15 at week 52 | 1798 mean fluorescence intensity |
Comparison: within-group analysis of change in GPR15 from baseline to week 52p-value: 0.23Mixed Models Analysis
Comparison: within-group analysis of change in GPR15 from baseline to week 58p-value: 0.12Mixed Models Analysis
Comparison: within-group analysis of change in GPR15 from week 52 to week 58p-value: 0.79Mixed Models Analysis
Comparison: within-group analysis of change in GPR15 from baseline to week 52p-value: 0.29Mixed Models Analysis
Comparison: within-group analysis of change in GPR15 from baseline to week 58p-value: 0.29Mixed Models Analysis
Comparison: within-group analysis of change in GPR15 from week 52 to week 58p-value: 0.42Mixed Models Analysis