Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema

NCT00097695 | Completed Phase 3 Results

• 2 other identifiers: JE049 #2103FAST1
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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).

Conditions

Angioedema

Keywords

Hereditary Angioedema; C1 inhibitor deficiency; HAE; Icatibant; Bradykinin antagonist; acute attack; subcutaneous

Outcome Measures

Primary Outcomes (1)

• Time to Onset of Symptom Relief (TOSR)

  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.

  5 days

Secondary Outcomes (2)

• Time to Regression (Start of Improvement) According to Patient

  5 days

• Time to Almost Complete Symptom Relief

  5 days

Study Arms (4)

Icatibant- Randomized

EXPERIMENTAL

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

Drug: Icatibant

Placebo-Randomized

PLACEBO COMPARATOR

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

Drug: Placebo

Controlled Open-label / laryngeal attack

EXPERIMENTAL

Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.

Drug: Icatibant

Untreated Patients at the baseline

EXPERIMENTAL

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

Interventions

Icatibant DRUG

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

Also known as: Brand name, Firazyr®

Controlled Open-label / laryngeal attack; Icatibant- Randomized; Untreated Patients at the baseline

Placebo DRUG

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

Placebo-Randomized

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

Georgetown University Hospital, Lombardi Cancer Center

Washington D.C., District of Columbia, 20007-2197, United States

Location

Related Publications (2)

• 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.

  PMID: 24749847 DERIVED

• 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.

  PMID: 20818888 DERIVED

MeSH Terms

Conditions

Angioedema; Angioedemas, Hereditary

Interventions

icatibant

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2004
• First Posted: November 29, 2004
• Study Start: December 28, 2004
• Primary Completion: July 17, 2006
• Study Completion: July 17, 2006
• Last Updated: June 9, 2021
• Results First Posted: December 24, 2013

Record last verified: 2021-05

Locations

US (1)