Efficacy of Tezepelumab in Peanut Oral Immunotherapy (ZENITH)

Efficacy of Tezepelumab in Peanut Oral Immunotherapy: a Double-Blind, Randomized, Placebo-Controlled Trial

The proposed study is a proof-of-concept Phase 2, double-blind, randomized placebo-controlled clinical trial evaluating the safety and efficacy of tezepelumab and peanut Oral Immunotherapy (OIT) for the treatment of peanut allergy. Study participation is divided into 3 periods: (i) a monotherapy period comprised of injections of either Tezepelumab or placebo from week 0 to week 8, (ii) followed by a combination therapy period comprised of 56 weeks during which peanut OIT is built up and maintained, and (iii) a treatment withdrawal period comprised of 12 weeks. This study will enroll 62 peanut-allergic individuals from 12 to 55 years of age who experience dose-limiting symptoms to <=100 mg of peanut protein in a single dose (<= 144 mg cumulative dose) as assessed by DBPCFC.

The primary objective is to determine whether 56 weeks of tezepelumab plus peanut OIT as compared to 56 weeks of placebo plus peanut OIT induces sustained unresponsiveness to peanut 12 weeks after stopping combination therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Peanut Allergy
• Intervention / Treatment: Biological: Tezepelumab; Drug: Peanut Oral Immunotherapy (OIT); Biological: Placebo for Tezepelumab

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital Research Institute: Department of Pediatrics, Allergy & Immunology
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles: Department of Medicine, Division of Clinical Immunology and Allergy
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Children's Center: Department of Allergy & Immunology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital: Department of Medicine: Allergy & Clinical Immunology Unit
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital: Allergy and Asthma Program
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • The University of Michigan: Division of Allergy and Clinical Immunology
  • New York
    • New York, New York, United States, 10029-6574
      • Icahn School of Medicine at Mount Sinai: Department of Pediatrics Allergy & Immunology
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • North Carolina Children's Hospital: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center: Division of Allergy and Immunology
  • Texas
    • Dallas, Texas, United States, 75390-9063
      • University of Texas Southwestern Medical Center: Division of Allergy and Immunology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant and/or parent/legal guardian must be able to understand and provide informed consent (parental permission and informed assent of minor, if applicable).
2. Age 12 to 55 years inclusive with a personal history of an allergic reaction to peanut ingestion
3. A positive reaction at or below ingestion of 100 mg of peanut protein in a single dose (≤ 144 mg cumulative dose) during the Screening DBPCFC
4. A negative challenge to the placebo (oat) during the Screening DBPCFC

5. Sensitization to peanut as evidenced by either one of the following:

   1. positive sIgE to Ara h2 ≥ 0.35 kU/L by ImmunoCAPTM testing, or
   2. wheal ≥ 3 mm on skin prick test to peanut extract compared to a negative control
6. Female participants of childbearing potential must have a negative pregnancy test upon study entry
7. Female participants with reproductive potential must agree to use an FDA approved method of contraception for the duration of the study
8. Willing and able to comply with the study protocol requirements
9. Participants with other food allergies must agree to continue avoidance of these food items from their diet to avoid confounding the safety and efficacy data of the study

Exclusion Criteria:

1. Currently in build-up phase of aeroallergen immunotherapy
2. Current food allergen immunotherapy or use of any food allergen immunotherapy within the past 12 months
3. Pregnant, planning a pregnancy during the study, or breast-feeding
4. History of intolerance, hypersensitivity, or allergic reactions to tezepelumab, or the inactive ingredients (excipients) of tezepelumab, other IgG biologics, or rescue medications and their excipients
5. Allergy to oat (participant reported)
6. History of severe systemic allergic reaction to peanut with symptoms including the need for mechanical ventilation and/or severe hypotension requiring intensive care unit admission
7. Asthma requiring high dose inhaled corticosteroid therapy for control (2007 NHLBI Criteria Steps 5 or 6 in adults and adolescents)
8. History of a life-threatening asthma attack within 12 months prior to screening (e.g., requiring an ICU admission or intubation with mechanical ventilation), need for oral corticosteroids for asthma management within the last 6 months, or current Asthma Control Test score less than 19 at screening
9. History of ischemic cardiovascular disease or other cardiac disease, which, in the opinion of the site 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
10. History of eosinophilic gastrointestinal disease at screening
11. History of disease affecting the immune system such as autoimmune disease (e.g., systemic lupus erythematosus), immune complex disease (e.g., serum sickness), or immunodeficiency, which, in the opinion of the site 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
12. History of malignancy of any type, excluding basal cell and squamous cell cancers of the skin that only required surgical excision or in situ carcinoma of the cervix study provided that curative therapy was completed at least 12 months prior to screening
13. Current known helminth infection
14. Positive QuantiFERON - TB Gold test or TB Gold Plus, or T-SPOT® TB test unless the potential participant has been treated with appropriate chemoprophylaxis. In the case of an indeterminate or borderline Interferon Gamma Release Assay (IGRA), an IGRA may be repeated.

15. Any of the following:

    1. HIV
    2. Current or prior infection with hepatitis B virus (HBV)
    3. Current or prior infection with hepatitis C virus (HCV), except adequately treated HCV with sustained virologic response ≥ 12 weeks.

16. Active liver disease, defined as either:

    1. AST, ALT, and/or Alk phos >2x ULN, or
    2. other active liver disease which, in the opinion of the site 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

17. Any of the following:

    1. Current use of beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers
    2. Received any investigational product within the past 4 months or 5 half-lives (whichever is longer) prior to screening
    3. Received systemic corticosteroids within 14 days prior to screening
    4. Receipt of immunoglobulin or other blood product within 30 days prior to screening
    5. Receipt of live attenuated vaccine within 30 days prior to screening
    6. Use of an immunosuppressant or immunomodulating drug within 30 days prior to screening
    7. Use of biologics targeting the human immune system within the past 12 months prior to screening
    8. Use of any herbal medications, 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
18. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the site 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tezepelumab plus Peanut Oral Immunotherapy (OIT) Group; Eligible participants will be randomized in a 1:1 fashion to receive Tezepelumab during the monotherapy period of the trial. Throughout the combination therapy period, which also includes an OIT build-up and maintenance period, participants will remain on tezepelumab 210 mg every 4 weeks until reaching the final period of the trial, the withdrawal period.	Biological: Tezepelumab; Monotherapy Period: Participants randomized to tezepelumab will receive two subcutaneous (SQ) injections of tezepelumab 210 mg during the monotherapy period. Combination Therapy Period: Participants randomized to Tezepelumab will continue to receive Tezepelumab 210 mg every 4 weeks. Withdrawal Period: Participants will stop receiving Tezepelumab injections.; Drug: Peanut Oral Immunotherapy (OIT); Monotherapy Period: Not Applicable. Combination Therapy Period: During combination therapy period, each participant will start peanut OIT. Participants will start on a minimum of 0.1 mg peanut OIT, with starting dose depending on last tolerated dose from screening double-blind placebo-controlled food challenge (DBPCFC) and build to a maximum of 6 mg peanut OIT on the initial dose escalation (IDE) day. Participants will return every 2 weeks for dose escalation to a goal maintenance dose of 2000 mg peanut protein. Withdrawal Period: Participants will stop peanut OIT.
Placebo Comparator: Placebo for Tezepelumab plus peanut Oral Immunotherapy (OIT) Group; Eligible participants will be randomized in a 1:1 fashion to receive placebo for Tezepelumab during the monotherapy period of the trial. Throughout the combination therapy period, which also includes an OIT build-up and maintenance period, participants will remain on placebo for tezepelumab every 4 weeks until reaching the final period of the trial, the withdrawal period.	Drug: Peanut Oral Immunotherapy (OIT); Monotherapy Period: Not Applicable. Combination Therapy Period: During combination therapy period, each participant will start peanut OIT. Participants will start on a minimum of 0.1 mg peanut OIT, with starting dose depending on last tolerated dose from screening double-blind placebo-controlled food challenge (DBPCFC) and build to a maximum of 6 mg peanut OIT on the initial dose escalation (IDE) day. Participants will return every 2 weeks for dose escalation to a goal maintenance dose of 2000 mg peanut protein. Withdrawal Period: Participants will stop peanut OIT.; Biological: Placebo for Tezepelumab; Monotherapy Period: Participants randomized to placebo for tezepelumab will receive two subcutaneous (SQ) injections of placebo 210 mg during the monotherapy period. Combination Therapy Period: Participants randomized to placebo will continue to receive placebo for Tezepelumab every 4 weeks. Withdrawal Period: Participants will stop receiving placebo injections.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consumption of a cumulative dose of 4000 mg of peanut protein without dose-limiting symptoms during the open Oral Food Challenge (OFC)	The primary endpoint is sustained unresponsiveness to peanut 12 weeks after stopping combination therapy, as assessed by passing the open OFC to peanut at Week 76	At week 76

Secondary Outcome Measures

Outcome Measure	Time Frame
Highest single dose of peanut protein consumed without doselimiting symptoms during the open Oral Food Challenge (OFC)	At week 64 and 76
Consumption of a cumulative dose of 4000 mg of peanut protein without doselimiting symptoms during the open Oral Food Challenge (OFC)	At week 64
Highest cumulative dose of peanut protein consumed without dose limiting symptoms during the open Oral Food Challenge (OFC)	At week 64 and 76
An adverse event related to monotherapy	During 8 weeks of therapy
An adverse event related to combination therapy	During 56 weeks of therapy
An adverse event related to tezepelumab plus peanut Oral Immunotherapy (OIT) discontinuation	12 weeks after discontinuation of treatment
An adverse event related to placebo plus peanut Oral Immunotherapy (OIT) discontinuation	12 weeks after discontinuation of treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Rho Federal Systems Division, Inc.; Immune Tolerance Network (ITN); PPD Development, LP
• Investigators: Study Chair: Edwin H Kim, M.D., M.S., North Carolina Children's Hospital: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology; Study Chair: Sarita Patil, M.D., Massachusetts General Hospital: Department of Medicine: Allergy & Clinical Immunology Unit

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): September 16, 2028
• Study Completion (Estimated): September 16, 2028

Study Registration Dates

• First Submitted: June 3, 2025
• First Submitted That Met QC Criteria: June 3, 2025
• First Posted (Actual): June 11, 2025

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Peanut; Oral Immunotherapy; Tezepelumab
• Additional Relevant MeSH Terms: Nut and Peanut Hypersensitivity; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity; Peanut Hypersensitivity; Immunologic Factors; Physiological Effects of Drugs; tezepelumab
• Other Study ID Numbers: DAIT ITN097AD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
• IPD Sharing Time Frame: On average, within 24 months after database lock for the trial.
• IPD Sharing Access Criteria: Open access.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No