Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00097695
First received: November 26, 2004
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to assess the efficacy and safety of Icatibant, a bradykinin antagonist in the treatment of acute cutaneous and/or abdominal attacks in patients with hereditary angioedema (HAE).


Condition Intervention Phase
Angioedema
Drug: Icatibant
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double Blind, Placebo-Controlled, Multicenter Study of a Subcutaneous Formulation of Icatibant for the Treatment of Hereditary Angioedema

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Time to Onset of Symptom Relief (TOSR) [ Time Frame: 5 days ] [ Designated as safety issue: No ]

    The primary efficacy endpoint was TOSR assessed by the patient using a Visual Analogue Scale (VAS). The VAS is a scale used to measure intensity of each symptom of the attack at baseline and at the pre-determined time points throughout treatment period. It consists of a horizontal 10cm line, with the 0 point corresponding to a state where patient experiences no symptoms at all and the 10cm point represents the worst symptoms ever experienced by patient. The patient indicates his/her current state of symptoms by drawing a mark across the horizontal line.

    TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the 3 primary symptoms: cutaneous swelling, cutaneous skin, and abdominal pain.

    The primary symptom was based on the type of attack. For abdominal attacks, the single primary symptom was abdominal pain. For cutaneous attacks, the single primary symptom was either skin swelling or skin pain, whichever was most severe.



Secondary Outcome Measures:
  • Time to Regression (Start of Improvement) According to Patient [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    This parameter assessed the time to regression (start of improvement) of observable(visible) symptoms according to the patients. Patients were asked "Report date and time when you feel that your symptoms start to improve".

  • Time to Almost Complete Symptom Relief [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    The time to almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least 3 consecutive measurements for all symptom.


Enrollment: 84
Study Start Date: August 2004
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Icatibant- Randomized
Patients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.
Drug: Icatibant
30 mg (3mL) subcutaneous icatibant injection in the abdominal region
Other Name: Brand name, Firazyr®
Placebo Comparator: Placebo-Randomized
Patients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack.
Drug: Placebo
Solution for injection, matched to study drug Single dose: 3 mL
Other Name: Placebo
Experimental: Controlled Open-label / laryngeal attack
Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.
Drug: Icatibant
30 mg (3mL) subcutaneous icatibant injection in the abdominal region
Other Name: Brand name, Firazyr®
Experimental: Untreated Patients at the baseline
Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing (they were not treated during the Controlled phase but treated with icatibant during the Open Label Extension Phase (OLE) )
Drug: Icatibant
30 mg (3mL) subcutaneous icatibant injection in the abdominal region
Other Name: Brand name, Firazyr®

Detailed Description:

This Phase II/III study consisted of two parts: A controlled phase and An Open label extension(OLE) phase. The controlled phase describes the double blind part of the study and was intended to evaluate the efficacy of icatibant in decreasing the time to onset of symptom relief compared with placebo for the first treated cutaneous and/or abdominal attack in randomised patients. Patients experienced a laryngeal attack were not randomised, but treated with open label icatibant according to the controlled phase procedures and assessments. The outcome of this group was to be reported descriptively. After treatment of the first attack in the controlled phase, the patients were eligible to enter the OLE phase. In the OLE phase, patients who experienced angioedema attacks severe enough to warrant treatment were to be treated with s.c. icatibant as appropriate until the end of the study.The OLE phase became a modified open label extension where all 56 patients who had been randomised and the last randomised patient had concluded the double-blind phase. The modified open label extension period permitted treatment for patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the double blind phase was still ongoing.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age above 18 years;
  • Documented diagnosis of HAE Type I or II (confirmed complement 1 esterase inhibitor [C1-INH] deficiency);
  • Current edema be in the cutaneous, abdominal and/or laryngeal areas;
  • Current edema be moderate to severe according to the investigator's Symptom Score.

Exclusion Criteria:

  • Diagnosis of angioedema other than HAE, for example, acquired angioedema (AAE);
  • Participation in a clinical trial of another investigational medicinal product (IMP) within the past month;
  • Treatment with any pain medication since onset of the current edema attack;
  • Treatment with replacement therapy, including C1-INH products (e.g. human C1-INH preparations), less than 3 days from onset of the current edema attack;
  • Treatment with ACE inhibitors (e.g. Lotensin, Prinivil, Accupril);
  • Evidence of severe, symptomatic coronary artery disease based on medical history or screening examination;
  • Serious concomitant illnesses that the physician considers to be a contraindication for participation in the trial;
  • Pregnancy and/or breast-feeding.
  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: NCT00097695

Locations
United States, District of Columbia
Georgetown University Hospital, Lombardi Cancer Center
Washington, District of Columbia, United States, 20007-2197
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Francisco Bracho, MD Children's Hospital Los Angeles
  More Information

No publications provided by Shire

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00097695     History of Changes
Other Study ID Numbers: JE049 #2103, FAST1
Study First Received: November 26, 2004
Results First Received: January 24, 2011
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Shire:
Hereditary Angioedema
C1 inhibitor deficiency
HAE
Icatibant
Bradykinin antagonist
acute attack
subcutaneous

Additional relevant MeSH terms:
Angioedema
Angioedemas, Hereditary
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 01, 2014