IgE-Mediated Food Allergy, Peanut Allergy, Cow Milk Allergy, Egg Allergy
Conditions
Keywords
IgE-mediated food allergy,, peanut allergy,, milk allergy,, egg allergy,, remibrutinib
Brief summary
The purpose of this Phase III study is to evaluate the clinical efficacy and safety of remibrutinib in participants with peanut, or cow's milk ("milk", cooked and uncooked) or hen's egg ("egg", cooked and uncooked) immunoglobulin E (IgE)- mediated allergy in comparison to placebo.
Detailed description
This study is a Phase III, 52-week, multi-center, placebo controlled pivotal study to evaluate the efficacy and safety of remibrutinib compared to placebo in adolescent and adult participants with peanut, milk, or egg IgE-mediated allergy. This study will be conducted in 4 Sub-studies: Sub-study 1 to evaluate response to peanut allergen at Week 24, Sub-study 2 to evaluate response to milk allergen at Week 24, Sub-study 3 to evaluate response to egg allergen at Week 24, and Sub-study 4 to evaluate response to peanut or milk, or egg allergen at Week 4. Treatment period 1: Participants will receive one of the two treatment groups, double-blind remibrutinib or placebo, for a period up to 24 weeks for Sub-studies 1, 2, and 3, and up to 4 weeks for Sub-study 4. Treatment period 2: For all Sub-studies, the open label period starts at Week 24, except for Sub-study 4, where the open label period starts at Week 4. Participants from each Sub-study will continue in the study and receive, or initiate, active open label remibrutinib until Week 52. Following completion of the treatment period 2, eligible participants may enroll in a separate open-label post-trial access study and receive remibrutinib to evaluate long-term treatment effects. Participants who do not enroll in the post-trial access study will enter a 4-week safety follow-up period off treatment, during which adverse events will be monitored.
Interventions
DRUGRemibrutinib
Oral administration of remibrutinib.
DRUGPlacebo
Oral administration of placebo.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent and/or assent (where applicable) must be obtained prior to study participation. Participant (and parent/legal guardian for adolescents) must be able to understand and provide informed consent and assent, as applicable. If a minor participant providing assent reaches the age of legal majority (as defined by local law), he/she must be re-consented (ICF) at the next study visit. * Male or female participants who are 12 to 65 years of age, inclusive, at the time of signing informed consent/assent. * Positive allergen-specific (peanut, milk, or egg), IgE (≥ 0.35 kUA/L) at Screening Visit 1. * Positive Skin Prick Testing (SPT) for peanut, milk, or egg at Screening Visit 1. This is defined as the average diameter (longest diameter and mid-point orthogonal diameter) ≥ 4 mm wheal compared to the negative control. * A positive DBPCFC at baseline (Screening Visit 2), defined as the occurrence of dose-limiting symptoms at a single dose: * ≤ 100 mg of peanut allergen protein * ≤ 300 mg for milk or egg allergen protein * Participants must be able and willing to participate in the DBPCFC and must be willing to continue avoiding exposure to peanut, milk (cooked and uncooked), or egg (cooked and uncooked) and any other foods that they are allergic to throughout this study.
Exclusion criteria
* Previous use of remibrutinib or other Bruton Tyrosine Kinase (BTK) inhibitors. * History of hypersensitivity to study drug or its excipients or to drugs of similar chemical classes. * Hypersensitivity or intolerance to any of the matrix components used within the material for the DBPCFC. * Any occurrence of dose-limiting symptoms against placebo allergen at baseline DBPCFC (Screening Visit Part 1 and/or Part 2). * Medical examination, medical conditions or laboratory findings that, in the opinion of the investigator, renders the participant unsuitable for the study. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sub-study 1: Number of participants achieving response status (tolerated at least 600 mg of peanut protein) | Week 24 | Response status is defined as tolerating an oral dose of at least 600 mg peanut protein (1044 mg cumulative tolerated dose) without dose-limiting symptoms during the double-blind placebo-controlled food challenge (DBPCFC). |
| Sub-study 2: Number of participants achieving response status (tolerated at least 1000 mg of milk protein) | Week 24 | Response status is defined as tolerating an oral dose of at least 1000 mg milk protein (2044 mg cumulative tolerated dose) without dose-limiting symptoms during the double-blind placebo-controlled food challenge (DBPCFC). |
| Sub-study 3: Number of participants achieving response status (tolerated at least 1000 mg of egg protein) | Week 24 | Response status is defined as tolerating an oral dose of at least 1000 mg egg protein (2044 mg cumulative tolerated dose) without dose-limiting symptoms during the double-blind placebo-controlled food challenge (DBPCFC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sub-study 3: Change from baseline in Log10-Transformed Maximum Tolerated Single Dose of egg protein | Baseline and Week 24 | Change from baseline in log10-transformed maximum tolerated single dose of egg protein without dose-limiting symptoms during the DBPCFC. |
| Sub-study 1: Number of participants by Maximum Symptom Severity During Peanut Protein Challenge | Week 24 | Maximum severity of symptoms occurring at any challenge dose up to and including 1000 mg peanut protein during the DBPCFC. Symptom severity is categorized as None, Mild, Moderate, or Severe. |
| Sub-study 2: Number of participants by Maximum Symptom Severity During Milk Protein Challenge | Week 24 | Maximum severity of symptoms occurring at any challenge dose up to and including 1000 mg milk protein during the DBPCFC. Symptom severity is categorized as None, Mild, Moderate, or Severe. |
| Sub-study 3: Number of participants by Maximum Symptom Severity During Egg Protein Challenge | Week 24 | Maximum severity of symptoms occurring at any challenge dose up to and including 1000 mg egg protein during the DBPCFC. Symptom severity is categorized as None, Mild, Moderate, or Severe. |
| Sub-study 1: Number of participants achieving response status (tolerated at least 3000 mg of peanut protein) | Week 24 | Response status is defined as tolerating an oral dose of 3000 mg peanut protein (5044 mg cumulative tolerated dose) without dose-limiting symptoms during the DBPCFC. |
| Sub-study 2: Number of participants achieving response status (tolerated at least 3000 mg of milk protein) | Week 24 | Response status is defined as tolerating an oral dose of 3000 mg milk protein (5044 mg cumulative tolerated dose) without dose-limiting symptoms during the DBPCFC. |
| Sub-study 3: Number of participants achieving response status (tolerated at least 3000 mg of egg protein) | Week 24 | Response status is defined as tolerating an oral dose of 3000 mg egg protein (5044 mg cumulative tolerated dose) without dose-limiting symptoms during the DBPCFC. |
| Sub-study 4: Number of participants achieving combined response status (tolerated at least 600 mg of peanut protein, or at least 1000 mg of milk or egg protein) | Week 4 | Combined response status is defined as tolerating at least 600 mg peanut protein (1044 mg cumulative tolerated dose) or at least 1000 mg milk or egg protein (2044 mg cumulative tolerated dose), as applicable, without dose-limiting symptoms during the DBPCFC. |
| Sub-study 4: Number of participants achieving combined response status (tolerated at least 1000 mg of peanut, milk or egg protein) | Week 4 | Combined response status is defined as tolerating at least 1000 mg peanut, milk, or egg protein, as applicable (2044 mg cumulative tolerated dose), without dose-limiting symptoms during the DBPCFC. |
| Sub-study 4: Change from baseline in Log10-Transformed Maximum Tolerated Single Dose | Baseline and Week 4 | Combined change from baseline in log10-transformed maximum tolerated single dose of peanut, milk, or egg protein, as applicable, without dose-limiting symptoms during the DBPCFC. |
| Sub-study 4: Number of participants by Maximum Symptom Severity During Food Challenge | Week 4 | Combined maximum severity of symptoms occurring at any challenge dose up to and including 1000 mg peanut, milk, or egg protein, as applicable, during the DBPCFC. Symptom severity is categorized as None, Mild, Moderate, or Severe. |
| Sub-study 4: Number of participants achieving combined response status (tolerated at least 3000 mg of peanut, milk or egg protein) | Week 4 | Combined response status is defined as tolerating an oral dose of 3000 mg peanut, milk, or egg protein, as applicable (5044 mg cumulative tolerated dose), without dose-limiting symptoms during the DBPCFC. |
| Sub-study 1: Number of participants achieving response status (tolerated at least 1000 mg of peanut protein) | Week 24 | Response status is defined as tolerating an oral dose of at least 1000 mg peanut protein (2044 mg cumulative tolerated dose) without dose-limiting symptoms during the double-blind placebo-controlled food challenge (DBPCFC). |
| Sub-studies 1, 2, 3 and 4: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 56 weeks | Number of participants with AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs. |
| Sub-study 1: Change from baseline in Log10-Transformed Maximum Tolerated Single Dose of peanut protein | Baseline and Week 24 | Change from baseline in log10-transformed maximum tolerated single dose of peanut protein without dose-limiting symptoms during the DBPCFC. |
| Sub-study 2: Change from baseline in Log10-Transformed Maximum Tolerated Single Dose of milk protein | Baseline and Week 24 | Change from baseline in log10-transformed maximum tolerated single dose of milk protein without dose-limiting symptoms during the DBPCFC. |
Countries
United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed