Study of Efficacy, Safety and Tolerability of Remibrutinib in Adult Participants With an Allergy to Peanuts

Study Overview
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Brief Summary
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A study to evaluate the safety, efficacy and tolerability of remibrutinib at three doses versus placebo in adult participants who have a confirmed allergy to peanuts. The efficacy will be measured by the ability of participants to tolerate increasing doses of peanut protein during an oral food challenge after 1 month of study treatment.

Detailed Description
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This is a one month, phase 2, multi-center, randomized, investigator- and participant-blinded, placebo controlled study to assess the safety, efficacy and tolerability of remibrutinib (LOU064) in 3 doses of oral tablet twice a day in participants with a medically confirmed diagnosis of IgE-mediated peanut allergy. Participants will be randomized to remibrutinib low, medium or high dose for one-month treatment period (up to 5 weeks). Participants will have oral food challenges at the beginning of the study and at the end of the treatment period to assess their symptoms from increasing doses of peanut allergen.

Official Title
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A One Month, Investigator and Participant Blinded Study to Investigate the Efficacy and Safety of Remibrutinib (LOU064) at Multiple Dose Levels in Adult Participants With Peanut Allergy

Conditions
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Allergy, Peanut

Intervention / Treatment
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* Drug: remibrutinib
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medical History of allergy to peanuts Positive peanut IgE >= 0.35 kUA/L Positive Skin Prick test for peanut allergen during screening for study Positive Oral Food Challenge to peanut during screening for study Willingness to comply with study schedule and procedures and avoid other allergens during study period Exclusion Criteria: History of severe or life-threatening hypersensitivity event leading to ICU admission or intubation within 60 days of screening Uncontrolled asthma Bleeding risk or coagulation disorder(s) Use of anticoagulants or anti-platelets (aspirin or clopidogrel may be permitted) History of splenectomy Any significant disease that would put the safety of the patient at risk. This includes, but is not limited to: history of cancer, significant cardiac disease/history, hematology disorders, history of GI bleeding, active infectious process, liver disease, renal disease, immunologic disease (stable diabetes and thyroid disease may be permitted), alcohol or drug abuse, etc. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: remibrutinib low dose<br>remibrutinib oral tablet | Drug: remibrutinib<br>* oral tablets<br>* Other names: (LOU064);|
| Experimental: remibrutinib medium dose<br>remibrutinib oral tablet | Drug: remibrutinib<br>* oral tablets<br>* Other names: (LOU064);|
| Experimental: remibrutinib high dose<br>remibrutinib oral tablet | Drug: remibrutinib<br>* oral tablets<br>* Other names: (LOU064);|
| Experimental: placebo 3 week / remibrutinib low dose 1 week<br>placebo oral tablet/ remibrutinib oral tablet | Drug: remibrutinib<br>* oral tablets<br>* Other names: (LOU064);Drug: placebo<br>* oral tablets<br>|
| Placebo Comparator: placebo<br>oral tablet | Drug: placebo<br>* oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy or oral remibrutinib compared to placebo, as measured by the proportion of participants who can tolerate a single dose of >=600mg of peanut protein without dose-limiting symptoms during DBPCFC | Responder status defined as tolerating a single dose of >=600mg of peanut protein without dose-limiting symptoms during the DBPCFC | Baseline and Day 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy or oral remibrutinib compared to placebo, as measured by the proportion of participants who can tolerate a single dose of >=1000mg of peanut protein without dose-limiting symptoms during DBPCFC | Responder status defined as tolerating a single dose of >=1000mg of peanut protein without dose-limiting symptoms during the DBPCFC | Baseline, Days 26 and 28 | 
| Efficacy or oral remibrutinib compared to placebo, as measured by the proportion of participants who can tolerate a single dose of >=3000mg of peanut protein without dose-limiting symptoms during DBPCFC | Responder status defined as tolerating a single dose of >=3000mg of peanut protein without dose-limiting symptoms during the DBPCFC | Baseline, Days 26 and 28 | 
| Efficacy or oral remibrutinib compared to placebo as measured by the madimum symptoms severity at any single challenged dose up to and including 1000mg of peanut protein | Maximum severity of symptoms occurring at any challenge dose of peanut protein up to and including 1000mg during the DBPCFC | Baseline, Days 26 and 28 | 
| Efficacy of 3 weeks placebo treatment followed by 1 week of oral remibrutinib treatment compared to placebo as measured by the proportion of participants who can tolerate a single dose of >=600mg peanut protein during DBPCFC | Responder status defined as tolerating a single dose of >=600mg peanut protein without dose limiting symptoms during the DBPCFC | Baseline, Days 26 and 28 | 
| Effects of multiple doses of remibrutinib compared to placebo, as measured by multiple systemic biomarkers to inform on response to treatment or disease severity | Change from baseline at weeks 1 and 4 of peanut specific IgE and IgG4, including peanut components | Baseline, Days 26 and 28 | 
| Ability of remibrutinib to impact skin mast cells through the assessment of allergen-specific skin prick test | Change from screening in skin prick test wheal diameters | Baseline and Day 26 | 
| Cmax of remibrutinib | Remibrutinib concentrations in blood and PK parameter - Cmax | Day 8 and Day 25 | 
| AUClast of remibrutinib | Remibrutinib concentrations in blood and PK parameter - AUClast | Day 8 and Day 25 | 
| AUCtau of remibrutinib | Remibrutinib concentrations in blood and PK parameter - AUCtau | Day 8 and Day 25 | 
| Tmax of remibrutinib | Remibrutinib concentrations in blood and PK parameter - Tmax | Day 8 and Day 25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgE, Groundnut Hypersensitivity, Hypersensitivity, Peanut, Peanut Allergy, Food Allergy, Oral food challenge, Remibrutinib, BTKi