Omalizumab for Peanut Allergy

(OUtMATCH Trial)

No longer recruiting at 9 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

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

Must not be taking: Corticosteroids, Antidepressants, Beta-blockers

Disqualifiers: Severe asthma, Anaphylaxis, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help individuals with a peanut allergy and allergies to at least two other foods, such as milk or eggs, safely consume these foods without severe reactions. It tests the medication omalizumab, administered as an injection, to determine if it can reduce allergic responses when combined with oral immunotherapy. Participants are divided into groups to receive either omalizumab alone, omalizumab with oral immunotherapy, or a placebo. Those allergic to peanuts and at least two other foods, who frequently experience significant allergic reactions, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as oral, intramuscular, or intravenous corticosteroids, tricyclic antidepressants, beta-blockers, and monoclonal antibody therapies like omalizumab, within specific timeframes before screening. Additionally, you must be able to discontinue antihistamines for the required washout periods for skin prick tests or oral food challenges.

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

Previous studies have shown that omalizumab is generally safe for treating food allergies. Research indicates no new side effects when using omalizumab for multiple food allergies, and it functions similarly to its use in other conditions, with no severe allergic reactions (anaphylaxis) reported in these studies.

In contrast, multi-allergen oral immunotherapy (OIT) can cause allergic reactions. Some studies have shown a high rate of reactions, although they are often mild. However, OIT is considered relatively safe when administered in a hospital, where assistance is readily available if needed.

In summary, omalizumab is well-tolerated with no new safety concerns, while multi-allergen OIT can lead to allergic reactions, but these are usually manageable in a medical setting. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for peanut allergies involve strict avoidance of peanuts and, in some cases, carrying emergency epinephrine. However, Omalizumab offers a novel approach by targeting and neutralizing IgE, the antibody responsible for allergic reactions, thus potentially reducing the severity of allergic responses. Researchers are excited because Omalizumab is administered through subcutaneous injections, which could be more convenient and less invasive than oral immunotherapy. Additionally, the combination of Omalizumab with multi-allergen oral immunotherapy could enhance tolerance to peanuts and other allergens, offering hope for long-term relief from severe allergic reactions.

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

Research has shown that omalizumab can help treat multiple food allergies, including peanut allergies. In this trial, some participants will receive omalizumab as monotherapy, while others will receive a placebo. One study demonstrated that omalizumab allowed patients to tolerate more peanut protein without severe allergic reactions. Specifically, 68% of patients who received omalizumab were protected from moderate to severe allergic symptoms, compared to only 5% of those who received a placebo. Additionally, omalizumab increased the amount of peanut protein many patients could handle by six times. These findings suggest that omalizumab could help people with peanut and other food allergies safely consume more of these foods. ^{4 6 7 8 9}

Who Is on the Research Team?

Robert A. Wood, MD

Principal Investigator

Department of Pediatrics at the Johns Hopkins University School of Medicine

Sharon Chinthrajah, MD

Principal Investigator

Department of Medicine, Stanford University School of Medicine

Are You a Good Fit for This Trial?

This trial is for people aged 1-55 with peanut and at least two other specific food allergies (milk, egg, wheat, cashew, hazelnut, walnut). They must have a positive skin test and immunoglobulin E levels for these allergens. Participants should be near the research unit during the study and trained to use an epinephrine autoinjector. Women of childbearing age must not be pregnant or breastfeeding and agree to use contraception.

Inclusion Criteria

Positive SPT (≥4 mm wheal) to food

Plan to remain in the study area of an OUtMATCH clinical research unit (CRU) during the trial

You have allergies to at least two out of six specific foods (milk, egg, wheat, cashew, hazelnut, walnut). This is to ensure that participants are likely to maintain their allergies throughout the study and not develop tolerance to these foods.

Exclusion Criteria

Has a first-degree relative already enrolled in the study

You have conditions or factors that could affect the accuracy or understanding of the study results.

Current participation in another therapeutic or interventional clinical trial or participation within 90 days of Screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1: Omalizumab Treatment

Participants receive omalizumab or placebo by subcutaneous injection every 2 or 4 weeks for 16 to 20 weeks, followed by DBPCFCs to assess food tolerance.

16-20 weeks

Bi-weekly or monthly visits for injections

Stage 1: Open Label Extension (OLE)

First 60 participants receive 24 weeks of open label omalizumab to assess long-term effects on food allergy reactions.

24 weeks

Bi-weekly or monthly visits for injections

Stage 2: Omalizumab and OIT

Participants receive 8 weeks of open label omalizumab, followed by randomization to omalizumab with either multi-allergen OIT or placebo for 44 weeks.

52 weeks

Regular visits for treatment and monitoring

Stage 3: Long-term Follow-up

Participants receive a treatment plan based on DBPCFC results, including dietary instructions or rescue OIT, with a minimum of 12 months follow-up.

12 months

Periodic follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Double-Blind Placebo-Controlled Food Challenge Based Treatment
• Multi-Allergen Oral Immunotherapy
• Omalizumab

Trial Overview The study tests if omalizumab can help participants consume foods without symptoms compared to a placebo. It's randomized and double-blind: neither doctors nor patients know who gets real treatment or placebo. The focus is on tolerating peanuts and two other allergens after treatment.

How Is the Trial Designed?

Group I: Stage 3: DBPCFC Based Treatment Experimental Treatment 1 Intervention

DBPCFC Based Treatment-Long-term Follow-up Treatment Plan for Peanut and Each of the Two Other Participant-Specific Foods. Upon completion of the DBPCFCs at the end of Stage 1 OLE or Stage 2, each participant will receive a separate treatment plan for peanut and each of the two other participant-specific foods based on the results of the DBPCFCs. A treatment plan will include instructions for one of the following: * Long-term follow-up with dietary consumption of a food; * Long-term follow-up with avoidance of a food; or * Rescue OIT for a food. The treatment plan for each food may change throughout Stage 3 depending on a participant's response to treatment. Once a participant enters Stage 3, the participant will have a minimum of 12 months follow-up until at least December 2022. Note: Participants will be instructed to strictly avoid a food if they receive rescue OIT for the food during Stage 3.

Group II: Stage 2: Omalizumab-Facilitated OIT Experimental Treatment 2 Interventions

OIT: oral immunotherapy-Omalizumab as Adjunct Therapy to Multi-Allergen Oral Immunotherapy Participants randomized to open label omalizumab + Multi-allergen OIT for eight weeks, followed by placebo for omalizumab + Multi-allergen OIT for 44 weeks. Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

Group III: Stage 2: Omalizumab + Placebo OIT Experimental Treatment 2 Interventions

OIT: oral immunotherapy Participants randomized to open label omalizumab + placebo for Multi-allergen OIT for eight weeks, followed by omalizumab + placebo for Multi-allergen OIT for 44 weeks. Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

Group IV: Stage 2: Omalizumab Experimental Treatment 1 Intervention

Participants will receive eight weeks of treatment with open label omalizumab in accordance with the omalizumab dosing table specified in the study protocol, administered by subcutaneous injection. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table. After completion of eight weeks of open label omalizumab, participants will be randomized 1:1 to either: * Omalizumab-facilitated oral immunotherapy (OIT): Open label omalizumab + Multi-allergen OIT for eight weeks, followed by placebo for omalizumab + Multi-allergen OIT for 44 weeks OR * Omalizumab + placebo OIT: Open label omalizumab + placebo for Multi-allergen OIT for eight weeks, followed by omalizumab + placebo for Multi-allergen OIT for 44 weeks. Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

Group V: Stage 1:Omalizumab as Monotherapy Experimental Treatment 1 Intervention

Eligible participants are randomized to receive omalizumab by subcutaneous injection either every 2 weeks or every 4 weeks for 16 to 20 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table. After 16 weeks of treatment, each participant will complete double-blind placebo-controlled food challenge (DBPCFCs) to each of their three specific foods to a cumulative dose of 6044 mg protein of each food. Throughout Stage 1, each participant will be instructed to strictly avoid all foods to which they are allergic. The first 60 participants who complete all four DBPCFCs at the end of Stage 1 will participate in the Stage 1 Open Label Extension (OLE).All other participants who complete all four DBPCFCs will move Stage 2 of the study.

Group VI: Stage 1: Omalizumab OLE Experimental Treatment 1 Intervention

OLE: Open Label Extension, Long-Term Treatment with Omalizumab. Participants will receive 24 weeks of open label omalizumab in accordance with the omalizumab dosing table defined in the study protocol. Omalizumab is administered by subcutaneous injection either every 2 weeks or every 4 weeks for 24 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table. After 24 weeks of treatment, each participant will complete DBPCFCs to each of their three specific foods to a cumulative dose of 8044 mg protein of each food. Each participant who completes all four DBPCFCs at the end of the Stage 1 OLE will move on to Stage 3 of the study. Throughout Stage 1 OLE, each participant will be instructed to strictly avoid all foods to which they are allergic.

Group VII: Stage 1: Placebo for Omalizumab as Monotherapy Placebo Group 1 Intervention

Eligible participants are randomized to receive placebo for omalizumab by subcutaneous injection either every 2 weeks or every 4 weeks for 16 to 20 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table. After 16 weeks of treatment, each participant will complete DBPCFCs to each of their three specific foods to a cumulative dose of 6044 mg protein of each food. Throughout Stage 1, each participant will be instructed to strictly avoid all foods to which they are allergic. The first 60 participants who complete all four DBPCFCs at the end of Stage 1 will participate in the Stage 1 OLE. All other participants who complete all four DBPCFCs will move Stage 2 of the study.

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+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a study of 15 children with severe asthma, treatment with omalizumab significantly increased food allergen thresholds, allowing 70.4% of subjects to tolerate previously problematic foods without oral immunotherapy.

The quality of life for patients improved markedly, as indicated by a significant increase in Pediatric Quality of Life Inventory scores, alongside a dramatic reduction in allergic reactions from 47 to just 2 over the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Omalizumab on Food Allergy in Patients Treated for Asthma: A Real-Life Study. Fiocchi, A., Artesani, MC., Riccardi, C., et al.[2020]

Omalizumab, when used alongside food allergen oral immunotherapy (OIT) for allergies like milk and peanuts, can help patients reach maintenance dosing faster and reduce adverse events, although serious side effects can still occur.

There is a risk of increased allergic reactivity after stopping omalizumab, and many patients have discontinued treatment, highlighting the need for more research to improve safety and identify the best candidates for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab as an adjuvant in food allergen immunotherapy. Dantzer, JA., Wood, RA.[2021]

In a phase 1 trial involving 15 participants (5 healthy adults and 10 peanut-allergic adults), the rectal administration of the modified peanut protein vaccine EMP-123 showed no significant adverse effects in healthy volunteers, but 50% of peanut-allergic subjects experienced adverse reactions, including severe allergic reactions in 20%.

Despite the adverse reactions, the treatment led to significant reductions in peanut skin test responses and basophil activation, indicating some immunologic effects, although no significant changes were observed in total IgE or peanut-specific IgE levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy. Wood, RA., Sicherer, SH., Burks, AW., et al.[2021]

Omalizumab, an FDA-approved monoclonal antibody for allergic asthma, works by binding to IgE, which may also help patients with food allergies by allowing them to tolerate higher amounts of allergens during treatment.

In clinical trials, omalizumab has shown promise as an adjunct therapy in food allergy immunotherapy, enabling patients to receive higher doses more quickly, but further large-scale studies are needed to confirm its efficacy and identify the best candidates for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of omalizumab in the treatment of food allergy and anaphylaxis. Lieberman, JA., Chehade, M.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11250439/

Efficacy, effectiveness and other patient-centered ... These results illustrated that proven peanut allergy was persistent over years and that the desensitization outcome had similar success rates to reports in ...

2. aaaai.org aaaai.org/tools-for-the-public/conditions-library/allergies/the-current-state-of-oral-immunotherapy

The Current State of Oral Immunotherapy Peanut, egg and milk OIT have been shown to desensitize approximately 60 to 80% of patients studied. Desensitization rates for other foods have not been as ...

3. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2300145

Oral Immunotherapy for Peanut Allergy in Children 1 to Less ... All other efficacy outcomes reported ... Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/all.16493

Oral Immunotherapy in Peanut‐Allergic Adults Using Real‐ ... Peanut oral immunotherapy (OIT) has shown effectiveness in achieving desensitization of children; however, evidence in adults is lacking.

5. jacionline.org jacionline.org/article/S0091-6749(12)03000-X/fulltext

Efficacy of Oral Immunotherapy in Patients with Multiple ... In this ongoing trial, 8 subjects have so far reached a threshold of 4000 mg to at least one of their food allergens in 88.5 weeks (median, with range of 70 to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24428859/

Safety and feasibility of oral immunotherapy to multiple ... Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11250201/

A review of the safety of oral immunotherapy in clinical trial ... Allergic reactions, including anaphylaxis, are also common during OIT, with an overall adverse event frequency as high as 98.7% in subjects observed in peanut ...

8. aacijournal.biomedcentral.com aacijournal.biomedcentral.com/articles/10.1186/1710-1492-10-1

Safety and feasibility of oral immunotherapy to multiple ... Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213219824009516

Safety and Feasibility of Peanut, Tree Nut, and Sesame ... No increased adverse outcomes were observed on multifood OIT. Of the 59 initial oral food challenges, objective reactions occurred during 42 challenges, most ...