A Pharmacokinetic, Tolerability and Safety Study of Icatibant in Children and Adolescents With Hereditary Angioedema

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Shire
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01386658
First received: June 28, 2011
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Hereditary Angioedema
Drug: icatibant
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 30
Study Start Date: December 2011
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Icatibant Drug: icatibant
Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg
Other Name: Firazyr

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Two through <18 years of age at the time of first HAE attack.

    • Prepubertal and pubertal/postpubertal subjects experiencing an HAE attack.
    • Pubertal/postpubertal subjects with HAE who are treated with icatibant, but not during an attack.
  2. Documented diagnosis of HAE Type I or II.
  3. Informed consent (and subject assent as appropriate) signed by the subject's parent(s)or legal guardian(s).

Exclusion Criteria:

  1. Diagnosis of angioedema other than HAE.
  2. Participation in another clinical trial that involves the use of any investigational product (drug or device)within 30 days prior to study enrollment or at any time during the study.
  3. Any known factor/disease that might interfere with the treatment compliance, study conduct,or result interpretation.
  4. Congenital or acquired cardiac anomalies that interfere significantly with cardiac function.
  5. Treatment with ACE inhibitors within 7 days prior to treatment.
  6. Use of hormonal contraception within the 90 days prior to treatment.
  7. Androgen use (eg, stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) within the 90 days prior to treatment.
  8. Pregnancy or breastfeeding.
  9. A physical condition that interferes with pubertal status determination.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01386658

  Show 30 Study Locations
Sponsors and Collaborators
Shire
Investigators
Study Director: Alan Kimura, M.D. Shire Human Genetic Therapies, Inc.
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01386658     History of Changes
Other Study ID Numbers: HGT-FIR-086, 2011-003825-81
Study First Received: June 28, 2011
Last Updated: July 21, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Shire:
Hereditary angioedema
HAE
Pediatric
Children
Safety
Efficacy
Pharmacokinetics
Firazyr
icatibant

Additional relevant MeSH terms:
Angioedemas, Hereditary
Angioedema
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn
Icatibant
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014