Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema

NCT ID: NCT00097695

Last Updated: 2021-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-28
• Study Completion Date: 2006-07-17

Brief Summary

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).

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.

Conditions

Angioedema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Icatibant- Randomized

Patients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.

Group Type: EXPERIMENTAL

Icatibant

Intervention Type: DRUG

30 mg (3mL) subcutaneous icatibant injection in the abdominal region

Placebo-Randomized

Patients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution for injection, matched to study drug Single dose: 3 mL

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.

Group Type: EXPERIMENTAL

Icatibant

Intervention Type: DRUG

30 mg (3mL) subcutaneous icatibant injection in the abdominal region

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) )

Group Type: EXPERIMENTAL

Icatibant

Intervention Type: DRUG

30 mg (3mL) subcutaneous icatibant injection in the abdominal region

Interventions

Icatibant

30 mg (3mL) subcutaneous icatibant injection in the abdominal region

Intervention Type: DRUG

Placebo

Solution for injection, matched to study drug Single dose: 3 mL

Intervention Type: DRUG

Other Intervention Names

Brand name, Firazyr®

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Georgetown University Hospital, Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Countries

United States

References

Malbran A, Riedl M, Ritchie B, Smith WB, Yang W, Banerji A, Hebert J, Gleich GJ, Hurewitz D, Jacobson KW, Bernstein JA, Khan DA, Kirkpatrick CH, Resnick D, Li H, Fernandez Romero DS, Lumry W. Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial. Clin Exp Immunol. 2014 Aug;177(2):544-53. doi: 10.1111/cei.12358.

Reference Type: DERIVED

PMID: 24749847 (View on PubMed)

Cicardi M, Banerji A, Bracho F, Malbran A, Rosenkranz B, Riedl M, Bork K, Lumry W, Aberer W, Bier H, Bas M, Greve J, Hoffmann TK, Farkas H, Reshef A, Ritchie B, Yang W, Grabbe J, Kivity S, Kreuz W, Levy RJ, Luger T, Obtulowicz K, Schmid-Grendelmeier P, Bull C, Sitkauskiene B, Smith WB, Toubi E, Werner S, Anne S, Bjorkander J, Bouillet L, Cillari E, Hurewitz D, Jacobson KW, Katelaris CH, Maurer M, Merk H, Bernstein JA, Feighery C, Floccard B, Gleich G, Hebert J, Kaatz M, Keith P, Kirkpatrick CH, Langton D, Martin L, Pichler C, Resnick D, Wombolt D, Fernandez Romero DS, Zanichelli A, Arcoleo F, Knolle J, Kravec I, Dong L, Zimmermann J, Rosen K, Fan WT. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):532-41. doi: 10.1056/NEJMoa0906393.

Reference Type: DERIVED

PMID: 20818888 (View on PubMed)

Other Identifiers

FAST1

Identifier Type: OTHER

Identifier Source: secondary_id

JE049 #2103

Identifier Type: -

Identifier Source: org_study_id