Clinical trial NCT06369467: Short-Term Linvoseltamab Treatment on Top of Chronic Dupilumab Treatment for Adults With Severe Immunoglobulin E (IgE)-Mediated Food Allergy
Official title: A Phase 1 Dose-Escalation Study in Adults With Severe IgE-Mediated Food Allergy, to Assess the Safety, Tolerability, and Pharmacodynamic Effects of Short-Term Linvoseltamab Treatment, a BCMAxCD3 Bispecific Antibody to Induce T-Cell Killing of IgE Producing Plasma Cells, on Top of Chronic Dupilumab Treatment, to Prevent the Formation of New IgE Producing Plasma Cells
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Food Allergy
Keywords: Severe Immunoglobulin E (IgE)-Mediated Food Allergy
Peanut
Hazelnut
Walnut
Cashew
Milk
Egg/egg white
Soy
Wheat
Sesame
Cod
Salmon
Tuna
Lobster
Crab
Shrimp
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-04-17
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is researching an experimental drug called linvoseltamab combined with another drug called dupilumab. The study is looking at patients who have severe IgE-mediated food allergy. If the patient has an allergy, the body's defense system (immune system) overreacts to an allergen (eg, certain foods like peanuts, milk, shellfish) by making antibodies called IgE. An antibody is a protein that allows the immune system to find and fight off things the body does not recognize (allergens). IgE antibodies are sent out by cells like plasma cells. These antibodies and allergens bind to other cells that send out chemicals, causing an allergic reaction. The aim of the study is to see what side effects happen when linvoseltamab is combined with dupilumab.

The study is looking at several other research questions, including:

* What side effects may happen from taking the study drugs
* Does linvoseltamab combined with dupilumab affect other types of antibodies in the blood at different times
* How much study drug(s) is in the blood at different times


Eligibility criteria: Key Inclusion Criteria:

1. Clinical history of documented, ongoing, severe IgE-mediated allergy to food (peanut, hazelnut, walnut, cashew, milk, egg/egg white, soy, wheat, sesame, cod, salmon, tuna, lobster, crab and/or shrimp; documented symptom\[s\] of anaphylaxis due to exposure)
2. History of physician reported anaphylaxis to food requiring epinephrine administration and/or requiring an emergency visit or inpatient hospitalization
3. Participants with dupilumab-indicated atopic dermatitis (AD) must be receiving DUPIXENT as standard of care for the treatment of AD for a minimum of 12 weeks prior to screening OR Participants with dupilumab-indicated eosinophilic esophagitis (EoE) must be receiving DUPIXENT as standard of care for the treatment of EoE for a minimum of 12 weeks prior to screening OR Must be willing to initiate dupilumab treatment for food allergy
4. Participants initiating dupilumab treatment must agree to remain on dupilumab for the duration of the combination study treatment and safety follow-up periods. Participants who elect to enter the linvoseltamab re-dosing period, must also remain on continuous dupilumab treatment as outlined. Participants on commercial DUPIXENT must agree to remain on their prescribed dose, as described in the protocol, for the duration of the combination study treatment period
5. Participant must be willing to use an epinephrine auto-injector device
6. Participant must be willing to receive booster and/or re-vaccination(s), including for live (attenuated) vaccinations, based on results of vaccine antibody titers and investigator opinion
7. Has a body mass index between 18 and 32 kilogram per square metre (kg/m2), inclusive

Key Exclusion Criteria:

1. Pregnant or breastfeeding women
2. History of chronic disease (other than AD or EoE) requiring therapy (eg, heart disease, diabetes, hypertension) that, in the opinion of the principal investigator, would represent a risk to the participant's health or safety in this study or the participant's ability to comply with the study protocol. Participants on DUPIXENT for conditions other than AD or EoE (eg, asthma, chronic rhinosinusitis with nasal polyps, prurigo nodularis, etc) are excluded
3. Known or suspected progressive multifocal leukoencephalopathy (PML), or history of PML, neurodegenerative condition, central nervous system (CNS) movement disorder, or seizure within 12 months prior to Day 1
4. Recent history (within past 30 days) of a grade 3 or grade 4 gastrointestinal bleed, history of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation
5. History of moderate or severe asthma based on the Global Initiative for Asthma (GINA) guidelines
6. Pre-bronchodilator forced expiratory volume in the first second (FEV1) \<80% of predicted using local reference values
7. Any prior exposure to a B-cell maturation antigen (BCMA) targeted therapy
8. Use of systemic corticosteroids within 2 months prior to screening
9. Use of other forms of allergen immunotherapy (eg, oral, SC, patch, or sublingual) or immunomodulatory therapy (not including corticosteroids) within 4 months prior to screening
10. Unwilling to discontinue use of antihistamines within 5 days prior to screening and within 5 days prior to skin prick test (SPT)
11. Hypersensitivity to epinephrine and any of the excipients in the epinephrine product
12. Within the previous 2 months of the screening visit has a history of bacterial, protozoal, viral or parasite infection requiring hospitalization or treatment with IV anti-infectives
13. Known history of human immunodeficiency virus (HIV) infection or HIV seropositivity at the screening visit

NOTE: Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From the initial first dose of linvoseltamab through the end of week 30
measure: Severity of TEAEs
timeFrame: From the initial first dose of linvoseltamab through the end of week 30
measure: Incidence of Adverse Event of Special Interest (AESIs)
timeFrame: From the initial first dose of linvoseltamab through the end of week 30
measure: Severity of AESIs
timeFrame: From the initial first dose of linvoseltamab through the end of week 30
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: From the initial first dose of linvoseltamab through the end of week 30
measure: Severity of SAEs
timeFrame: From the initial first dose of linvoseltamab through the end of week 30
Secondary outcomes:
measure: Absolute change in the serum concentration of total IgE over time
timeFrame: Baseline to the end of week 30
measure: Percent change in the serum concentration of total IgE over time
timeFrame: Baseline to the end of week 30
measure: Time to reach unquantifiable total serum IgE concentration
timeFrame: Through the end of week 30
measure: Time to reach baseline level and/or the lower limit of the normal ranges of serum IgG
timeFrame: Through the end of week 30
measure: Time to reach baseline level and/or the lower limit of the normal ranges of serum immunoglobulin M (IgM)
timeFrame: Through the end of week 30
measure: Time to reach baseline level and/or the lower limit of the normal ranges of serum immunoglobulin A (IgA)
timeFrame: Through the end of week 30
measure: Incidence of participants with unquantifiable concentrations of serum total IgE
timeFrame: Through the end of week 30
measure: Absolute change in the serum concentration of food allergen-specific IgE
timeFrame: Baseline through the end of week 30
measure: Percent change in the serum concentration of food allergen-specific IgE
timeFrame: Baseline through the end of week 30
measure: Time to reach unquantifiable food allergen-specific serum IgE levels
timeFrame: Through the end of week 30
measure: Incidence of TEAEs
timeFrame: Following the combination study treatment period up to approximately 176 weeks
measure: Severity of TEAEs
timeFrame: Following the combination study treatment period up to approximately 176 weeks
measure: Incidence of AESIs
timeFrame: Following the combination study treatment period up to approximately 176 weeks
measure: Severity of AESIs
timeFrame: Following the combination study treatment period up to approximately 176 weeks
measure: Incidence of SAEs
timeFrame: Following the combination study treatment period up to approximately 176 weeks
measure: Severity of SAEs
timeFrame: Following the combination study treatment period up to approximately 176 weeks
Other outcomes:
Locations:
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University- Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra- Pamplona
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: