A Pharmacokinetic, Tolerability and Safety Study of Icatibant in Children and Adolescents With Hereditary Angioedema
HGT-FIR-086 is a multicenter, open-label, non-randomized, single-arm study to evaluate the Pharmacokinetics, tolerability, and safety including effect on reproductive hormones, of a single subcutaneous, (SC) administration of icatibant in approximately 30 pediatric subjects with Hereditary Angioedema (HAE) during an initial acute attack.
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicenter, Open-Label, Non-Randomized Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Single Subcutaneous Administration of Icatibant in Children and Adolescents With Hereditary Angioedema|
- Pharmacokinetic (PK) Profile after a single SC injection (in prepubertal children with an acute attack of HAE and pubertal/postpubertal children with or without an acute attack of HAE) [ Time Frame: Administration through 6 hours ] [ Designated as safety issue: No ]PK parameter estimates will include, where appropriate: actual icatibant and metabolite concentrations at each sampling time, time to peak concentration (Tmax), actual peak (Cmax) and minimum (Cmin) concentrations, clearance (CL/F), actual area under the plasma concentration-time-curve (AUC0-last and AUC0-inf), mean residence time (MRT), volume of distribution at steady state (Vss/F) and elimination half-life (t1/2).
- Safety of a single SC dose of icatibant [ Time Frame: Treatment through day 90 ] [ Designated as safety issue: Yes ]Safety and tolerability will be assessed by standard criteria including injection site reactions, adverse events, vital signs, ECG recordings, physical examination, clinical laboratory parameters (serum chemistry [including liver function tests], hematology, urinalysis), reproductive hormone levels, and immunogenicity (presence of anti-icatibant antibodies).
- Time to onset of relief of symptoms and time to minimal symptoms, as measured by investigator- and subject-reported outcomes for subjects who have experienced HAE attack only [ Time Frame: Treatment through 8 hours ] [ Designated as safety issue: No ]
- For subjects 2 to less than 18 years of age: investigator assessment and scoring of cutaneous, abdominal and laryngeal symptoms of acute HAE attacks by an investigator-rated symptom score.
- For subjects 4 years of age and older: subject self-assessment of HAE related pain using the Faces Pain Scale-Revised (FPS-R).
- For subjects less than 4 years of age: investigator assessment of HAE-related pain (cutaneous, abdominal and laryngeal) using a validated pain scale (Faces, Legs, Activity, Cry, and Consolability [FLACC]).
- Proportion of subjects with worsened intensity of clinical HAE symptoms between 2 and 4 hours after treatment with icatibant for subjects who have experienced HAE attack only [ Time Frame: Treatment through 4 hours ] [ Designated as safety issue: No ]
- Incidence of rescue medication use for subjects who have experienced HAE attack only [ Time Frame: Treatment through day 90 ] [ Designated as safety issue: No ]
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||July 2017|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg
Other Name: Firazyr
Study HGT-FIR-086 will enroll 30 subjects from 2 to less than 18 years of age, divided into 2 groups: prepubertal and pubertal/postpubertal. At least 10 prepubertal children and at least 20 adolescents (including 10 treated during a HAE attack) must be enrolled in the study.
After a qualifying screening period, the PK, safety/tolerability, and efficacy of treatment with SC icatibant will be evaluated in at least 20 subjects (10 prepubertal and 10 pubertal/postpubertal subjects) who present with cutaneous, abdominal, or laryngeal symptoms of an acute attack of HAE. The PK and safety/tolerability of SC icatibant will be evaluated in at least 10 additional pubertal/postpubertal subjects who meet screening criteria and receive treatment with SC icatibant in the absence of a current acute HAE attack.
The planned duration of active participation for subjects who present with an initial attack of acute HAE will consist of treatment with a single subcutaneous injection of icatibant on Day 1 through follow up at day 90.
After having received initial treatment with icatibant, either during or in the absence of an attack, at least 10 pubertal/postpubertal subjects who subsequently experience an acute HAE attack may continue to receive treatment with icatibant as a single SC administration per attack for a total of 3 eligible icatibant-treated attacks.
The period of active participation in the study for prepubertal subjects will be approximately 90 days, while that for pubertal/postpubertal subjects could be a maximum of approximately 270 or 360 days (3 separate active periods of approximately 90 days for those treated with icatibant during an attack; 4 separate active periods for those treated without an attack), with each active period separated by periods of inactive participation of variable duration.
Show 31 Study Locations
|Study Director:||Alan Kimura, M.D.||Shire Human Genetic Therapies, Inc.|