Tezepelumab + Peanut Oral Immunotherapy for Peanut Allergy

(ZENITH Trial)

Not yet recruiting at 9 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Beta-blockers, ACE inhibitors, ARBs, others

Disqualifiers: Severe asthma, Cardiovascular disease, Autoimmune disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining the drug tezepelumab (an experimental treatment) with peanut oral immunotherapy (OIT) can reduce sensitivity to peanuts, even after stopping the treatment. It consists of three stages: an initial period with injections of either tezepelumab or a placebo, followed by a combined therapy period with peanut OIT, and finally, a period without treatment. The trial seeks participants who have had allergic reactions to peanuts and cannot tolerate more than 100 mg of peanut protein without symptoms. Participants should not currently undergo other allergen immunotherapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop certain medications, such as beta-blockers, ACE inhibitors, and some immunosuppressants, before participating. If you're taking any of these, you'll need to stop them as specified in the exclusion criteria. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tezepelumab is generally well-tolerated in people. Earlier studies found it to be safe with few serious side effects, with the most common reactions being mild, such as headaches or a runny nose.

For peanut oral immunotherapy (OIT), studies have indicated that it can sometimes cause mild allergic reactions as the body adjusts to peanuts. However, serious reactions are rare and usually well-managed in a clinical setting.

Since this trial is in an early phase, the safety of using tezepelumab with peanut OIT is still under investigation. Reaching this phase suggests that earlier tests did not identify any major safety concerns. Participants should always consult doctors or trial staff if they have any concerns or questions about side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for peanut allergy?

Tezepelumab is unique because it targets a specific part of the immune system known as the thymic stromal lymphopoietin (TSLP). Unlike standard peanut allergy treatments that often involve avoiding peanuts or using oral immunotherapy alone, Tezepelumab works by modulating the immune response, potentially reducing allergic reactions. Researchers are excited about this treatment because it offers a new way to enhance the effectiveness of oral immunotherapy, potentially increasing tolerance to peanuts and improving safety for those with severe allergies.

What evidence suggests that this trial's treatments could be effective for peanut allergy?

Research shows that Tezepelumab might enhance the effectiveness of peanut oral immunotherapy (OIT) for treating peanut allergies. In this trial, participants will receive either Tezepelumab or a placebo during the monotherapy period. Studies have found that OIT alone can increase tolerance to peanuts, with 67% of participants able to consume 5 grams of peanuts after treatment. Tezepelumab, an antibody treatment, blocks a molecule involved in allergic reactions, potentially boosting OIT's effects. Early results suggest that combining Tezepelumab with OIT could help maintain reduced sensitivity to peanuts even after treatment ends. Although further research is necessary, this combination shows promise for those with severe peanut allergies. ^{1 2 3 4 6}

Who Is on the Research Team?

Sarita Patil, M.D.

Principal Investigator

Massachusetts General Hospital: Department of Medicine: Allergy & Clinical Immunology Unit

Edwin H Kim, M.D., M.S.

Principal Investigator

North Carolina Children's Hospital: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology

Are You a Good Fit for This Trial?

This trial is for people aged 12-55 with a peanut allergy who react to less than or equal to 100 mg of peanut protein. Participants must have had a reaction during a controlled food challenge. They can't join if they don't meet these criteria or have other conditions that could interfere with the study.

Inclusion Criteria

Positive reaction at or below ingestion of 100 mg of peanut protein in a single dose (<= 144 milligram cumulative dose) during the screening Double-Blind Placebo-Controlled Food Challenge (DBPCFC)

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

Negative challenge to the placebo (oat) during the Screening DBPCFC

Exclusion Criteria

Current use of beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers, received any investigational product within the past 4 months or 5 half-lives prior to screening, received systemic corticosteroids within 14 days prior to screening, receipt of immunoglobulin or other blood product within 30 days of screening, receipt of live attenuated vaccine within 30 days of informed consent, use of an immunosuppressant or immunomodulating drug within 30 days prior to screening, use of biologics targeting the human immune system within the past 12 months prior to screening, use of any herbal medications that may pose additional risks from participation in the study

Pregnant, planning a pregnancy during the study, or breast-feeding

Allergy to oat (participant reported)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy

Participants receive injections of either Tezepelumab or placebo

8 weeks

Bi-weekly visits (in-person)

Combination Therapy

Participants receive Tezepelumab or placebo along with peanut Oral Immunotherapy (OIT) build-up and maintenance

56 weeks

Monthly visits (in-person)

Treatment Withdrawal

Participants stop combination therapy to assess sustained unresponsiveness

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

Trial Overview The study tests Tezepelumab's effectiveness combined with Peanut Oral Immunotherapy (OIT) against a placebo in treating peanut allergies over three periods: initial Tezepelumab/placebo injections, combination therapy with OIT, and treatment withdrawal to assess sustained unresponsiveness.

How Is the Trial Designed?

Group I: Tezepelumab plus Peanut Oral Immunotherapy (OIT) Group Experimental Treatment 2 Interventions

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.

Group II: Placebo for Tezepelumab plus peanut Oral Immunotherapy (OIT) Group Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Rho Federal Systems Division, Inc.

Industry Sponsor

Trials

44

Recruited

15,000+

PPD Development, LP

Industry Sponsor

Immune Tolerance Network (ITN)

Collaborator

Trials

68

Recruited

7,900+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07015996

Efficacy of Tezepelumab in Peanut Oral Immunotherapy 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 ...

2. trials.foodallergy.org trials.foodallergy.org/trials/NCT07015996

Efficacy of Tezepelumab in Peanut Oral Immunotherapy 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 ...

3. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/e/NCT07015996.html

Efficacy of Tezepelumab in Peanut Oral Immunotherapy 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 ...

4. withpower.com withpower.com/trial/phase-2-peanut-hypersensitivity-8-2025-2fdac

Tezepelumab + Peanut Oral Immunotherapy for ... Trial Overview The study tests Tezepelumab's effectiveness combined with Peanut Oral Immunotherapy (OIT) against a placebo in treating peanut allergies over ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7223701/

Peanut Oral Immunotherapy: a Current Perspective - PMC The results showed that 85% of the OIT participants passed the build-up phase and 67% tolerated 5 g of peanuts during the post-treatment challenge. There was no ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40268292/

Oral Immunotherapy in Peanut-Allergic Adults Using Real- ... Conclusions: Peanut OIT appears to be an efficacious treatment for adults with peanut allergy. Further studies are needed for confirmation ...