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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01386658
Recruitment Status : Completed
First Posted : July 1, 2011
Last Update Posted : March 23, 2018
Information provided by (Responsible Party):

Brief Summary:
HGT-FIR-086 is a multicenter, open-label, non-randomized, single-arm study to evaluate the Pharmacokinetics, tolerability,safety, and efficacy 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 or disease Intervention/treatment Phase
Hereditary Angioedema (HAE) Drug: icatibant Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : November 1, 2011
Actual Primary Completion Date : March 12, 2018
Actual Study Completion Date : March 12, 2018

Arm Intervention/treatment
Experimental: Icatibant
Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg
Drug: icatibant
Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg
Other Name: Firazyr

Primary Outcome Measures :
  1. 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 ]
    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).

  2. Safety of a single SC dose of icatibant [ Time Frame: Treatment through day 90 ]
    Safety and tolerability will be assessed by standard criteria including injection site reactions, adverse events, vital signs, electrocardiogram (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 :
  1. Time to onset of relief of symptoms and time to minimal symptoms, as measured byinvestigator- and subject-reported outcomes (only for subjects treated with icatibant during a HAE attack) [ Time Frame: Treatment through 8 hours ]
    • 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 only: subject self-assessment of HAE related pain using the Faces Pain Scale-Revised (FPS-R).• For subjects less than 4 years of age only: investigator assessment of HAE-related pain (cutaneous, abdominal and laryngeal) using a validated pain scale (Faces, Legs, Activity, Cry, and Consolability [FLACC]).

  2. 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 ]
  3. Incidence of rescue medication use for subjects who have experienced HAE attack only [ Time Frame: Treatment through day 90 ]
    Rescue medications are only monitored through the current attack and not through 90 days

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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

    • Prepubertal and pubertal/postpubertal subjects experiencing and acute cutaneous, abdominal, or laryngeal HAE attack treated with icatibant as part of this study.
    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01386658

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Sponsors and Collaborators
Study Director: Study Physician Shire Orphan Therapies, LLC

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Shire Identifier: NCT01386658     History of Changes
Other Study ID Numbers: HGT-FIR-086
2011-003825-81 ( EudraCT Number )
First Posted: July 1, 2011    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: March 2018

Keywords provided by Shire:
Hereditary angioedema

Additional relevant MeSH terms:
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Immune System Diseases
Genetic Diseases, Inborn
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Bradykinin B2 Receptor Antagonists
Bradykinin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Vasodilator Agents