Allergy, Peanut
Conditions
Keywords
Groundnut Hypersensitivity, Hypersensitivity, Peanut, Peanut Allergy, Food Allergy, Oral food challenge, IgE, Remibrutinib, BTKi
Brief summary
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 was 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
This was a randomized, participant- and investigator-blinded, placebo-controlled study to assess the safety and clinical efficacy of oral LOU064 versus placebo across five treatment arms in participants with a medically confirmed diagnosis of IgE-mediated peanut allergy for one-month treatment period (up to 5 weeks). Participants had 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.
Interventions
DRUGLOU064
oral tablets
DRUGplacebo
oral tablets
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Tolerated a Single Dose of >= 600 mg (1044 mg Cumulative Tolerated Dose) of Peanut Protein Without Dose-limiting Symptoms | Week 4 | Responder rate was defined as the percentage of participants tolerating a single dose of \>= 600 mg (1044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the double blind placebo controlled food challenge (DBPCFC). The cumulative tolerated dose is the sum of the tolerated doses, not including the reactive dose. Dose-limiting symptoms indicate a true allergic reaction occurring during administration of a single dose of peanut protein at the DBPCFC that should preclude the administration of any further doses in the view of the investigator. Symptoms that require administration of any rescue medication were considered dose-limiting symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Tolerated a Single Dose of >= 1000 mg (2044 mg Cumulative Tolerated Dose) of Peanut Protein Without Dose-limiting Symptoms | Week 4 | Responder rate was defined as the percentage of participants tolerating a single dose of \>= 1000 mg (2044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the double blind placebo controlled food challenge (DBPCFC). The cumulative tolerated dose is the sum of the tolerated doses, not including the reactive dose. Dose-limiting symptoms indicate a true allergic reaction occurring during administration of a single dose of peanut protein at the DBPCFC that should preclude the administration of any further doses in the view of the investigator. Symptoms that require administration of any rescue medication were considered dose-limiting symptoms. |
| Percentage of Participants Who Tolerated a Single Dose of 3000 mg (5044 mg Cumulative Tolerated Dose) of Peanut Protein Without Dose-limiting Symptoms | Week 4 | Responder rate was defined as the percentage of participants tolerating a single dose of \>= 3000 mg (5044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the double blind placebo controlled food challenge (DBPCFC). The cumulative tolerated dose is the sum of the tolerated doses, not including the reactive dose. Dose-limiting symptoms indicate a true allergic reaction occurring during administration of a single dose of peanut protein at the DBPCFC that should preclude the administration of any further doses in the view of the investigator. Symptoms that require administration of any rescue medication were considered dose-limiting symptoms. |
| Percentage of Participants Who Tolerated a Single Dose of >= 600 mg (1044 mg Cumulative Tolerated Dose) of Peanut Protein Without Dose-limiting Symptoms - Placebo+LOU064 25 mg and Placebo | Week 4 | Responder rate was defined as the percentage of participants tolerating a single dose of \>= 600 mg (1044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the double blind placebo controlled food challenge (DBPCFC). The cumulative tolerated dose is the sum of the tolerated doses, not including the reactive dose. Dose-limiting symptoms indicate a true allergic reaction occurring during administration of a single dose of peanut protein at the DBPCFC that should preclude the administration of any further doses in the view of the investigator. Symptoms that require administration of any rescue medication were considered dose-limiting symptoms. |
| Number of Participants Presenting Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein up to and Including 3000mg During the DBPCFC | 4 weeks | Maximum severity of symptoms occurring at any challenge dose of peanut protein up to and including 3000 mg during the DBPCFC conducted at one month, will be categorized as 4 levels: None, Mild, Moderate, Severe. |
| Change From Baseline of Peanut-specific IgE (Including Peanut Components) | Baseline, Day 25 pre-dose and Day 31 (End of Study) | IgE is a soluble biomarker that provide LOU064 response to treatment and disease severity biomarkers. |
| Change From Baseline of Peanut-specific IgG4 (Including Peanut Components) | Baseline, Day 25 pre-dose and Day 31 (End of Study) | IgG4 is a soluble biomarker that provide LOU064 response to treatment and disease severity biomarkers. |
| Change From Screening in Allergen-specific Skin Prick Test (SPT) Mean Wheal Diameters | Baseline, Day 26 | An allergen specific skin prick test (SPT) is a commonly used diagnostic tool. In this study a titration SPT using peanut allergen provided additional information on the impact of Bruton's tyrosine kinase (BTK) suppression on skin mast cells. Skin reactions were recorded after 15 minutes of applying allergen to the pricked location. The size of the wheel and flare (the longest diameter and the midpoint orthogonal diameter) at each site were recorded. |
| Maximum Observed Blood Concentration (Cmax) of LOU064 | Day 8 and Day 25: pre-dose, 0.5, 1, 2, 3, 4 hours. | Cmax is the maximum (peak) observed blood concentration of LOU064 after dose administration. Pharmacokinetic parameters were calculated using a non-compartmental method (WinNonLin Version 8.3.4 or higher). The LOU064 concentration was determined by a validated Liquid chromatography-mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 0.1 ng/mL. |
| Area Under Blood Concentration-time Curve (AUClast) of LOU064 | Day 8 and Day 25: pre-dose, 0.5, 1, 2, 3, 4 hours. | AUClast is the area under the blood concentration-time curve from time zero to the time of last quantifiable concentration (tlast) of LOU064. Pharmacokinetic parameters were calculated using a non-compartmental method (WinNonLin Version 8.3.4 or higher). The LOU064 concentration was determined by a validated Liquid chromatography-mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 0.1 ng/mL. |
| Area Under Plasma Concentration-time Curve (AUCtau) of LOU064 | Day 8 and Day 25: pre-dose, 0.5, 1, 2, 3, 4 hours. | AUCtau is the area under the plasma concentration-time curve. Estimation of AUCtau values required extrapolation of the concentration-time profile from the last measured time-point at 4 h to the end of dosing interval at 12 h post-dose. In some cases, this extrapolation was not possible. For this reason, the number of participants with measurable AUCtau values was less when compared to those with AUClast. Pharmacokinetic parameters were calculated using a non-compartmental method (WinNonLin Version 8.3.4 or higher). The LOU064 concentration was determined by a validated Liquid chromatography-mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 0.1 ng/mL. |
| Time to Reach Maximum Observed Blood Concentration (Tmax) of LOU064 | Day 8 and Day 25: pre-dose, 0.5, 1, 2, 3, 4 hours. | Tmax is the time to reach maximum (peak) of LOU064 blood concentration after single-dose administration (time). Pharmacokinetic parameters were calculated using a non-compartmental method (WinNonLin Version 8.3.4 or higher). The LOU064 concentration was determined by a validated Liquid chromatography-mass spectrometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 0.1 ng/mL. |
| Number of Participants Presenting Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein up to and Including 1000mg During the DBPCFC | 4 weeks | Responder rate was defined as the percentage of participants tolerating a single dose of \>= 3000 mg (5044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the double blind placebo controlled food challenge (DBPCFC). The cumulative tolerated dose is the sum of the tolerated doses, not including the reactive dose. Dose-limiting symptoms indicate a true allergic reaction occurring during administration of a single dose of peanut protein at the DBPCFC that should preclude the administration of any further doses in the view of the investigator. Symptoms that require administration of any rescue medication were considered dose-limiting symptoms. |
Countries
United States
Participant flow
Recruitment details
Participants took part in 22 investigative sites in United States.
Pre-assignment details
The study consisted of a screening period of approximately 4 weeks.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 24.9 years STANDARD_DEVIATION 7.38 |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants |
| Race/Ethnicity, Customized White | 55 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 | 0 / 18 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 76 |
| other Total, other adverse events | 10 / 19 | 8 / 19 | 6 / 18 | 2 / 10 | 5 / 10 | 8 / 10 | 38 / 76 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 | 0 / 18 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 76 |
Outcome results
None listed