Trial Outcomes & Findings for Berotralstat Treatment in Children With Hereditary Angioedema (NCT NCT05453968)

A total of 29 pediatric participants were enrolled in the study at a total of 11 study sites in Austria, Canada, France, Germany, Italy, Israel, Poland, Spain and the United Kingdom (UK).

Participants were enrolled into a 12-week standard of care (SOC) period prior to initiating berotralstat. Participants were assigned to one of 4 cohorts based on body weight. Results contained herein are based on an interim analysis with data cutoff date of 11 September 2024 which was determined by the protocol defined event.

Berotralstat Treatment in Children With Hereditary Angioedema

AUC0-last is the area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration.

AUC0-6 is the area under the plasma concentration-time curve from time 0 to 6 hours.

Ctrough is the concentration at the end of a dosing interval of berotralstat.

Cmax is the maximum observed plasma concentration of berotralstat.

Tlast is the time of the last measurable concentration (Clast) of berotralstat collected over the sampling interval.

Tmax is the time taken to reach the maximum observed plasma concentration of berotralstat.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant. No causal relationship with study drug or with the clinical study itself is implied. An AE could be an unfavorable and unintended sign, symptom (including an abnormal laboratory finding), syndrome, or illness that developed or worsened during the clinical study. A serious adverse event (SAE) is any untoward medical occurrence resulting in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or other medically important event. TEAEs are AEs that occurred on/after first dose of berotralstat through 30 days post discontinuation of study treatment.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began \> 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began \> 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The adjusted attack rate was calculated as the number of adjusted attacks observed during a given period and standardized to number of attacks per month, where 1 month is defined as a 28-day (4 week) period.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began \> 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The duration of each participant-reported attack was calculated in hours, based on the start, and stop date and time of the adjusted attack (time the attack finished).

Adjusted attacks were assessed based on anatomical location. Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began \> 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. Anatomical locations were categorized as abdominal-only, non-abdominal peripheral, mixed, and laryngeal attacks.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began \> 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. Number of adjusted attacks treated with targeted HAE medications was assessed.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began \> 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. Proportion of adjusted attacks treated with targeted HAE medications was assessed.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc)?",were considered unique (attack began \> 24 hours from the end of the prior attack),and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The number of days with angioedema symptoms is the number of the days during the reporting period for which at least 1 symptom is reported during an adjusted HAE attack based on the start date and resolution date of an attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc)?",were considered unique (attack began \> 24 hours from the end of the prior attack),and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The proportion of days with angioedema symptoms was based on the number of days with reported symptoms and the number of days the participant was on treatment, where the number of days with angioedema symptoms is the number of the days during the reporting period for which at least 1 symptom is reported during an adjusted HAE attack based on the start date and resolution date of an attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began \> 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The severity was assessed by the parent/caregiver as negligible, mild, moderate or severe.

The total number of participants who discontinued the treatment due to perceived lack of efficacy of berotralstat were reported.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began \> 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of \> 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. Number of adjusted attacks that required hospitalization or clinic visits are reported.