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Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema

Primary Purpose

Angioedema

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Icatibant
Placebo
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Angioedema focused on measuring Hereditary Angioedema, C1 inhibitor deficiency, HAE, Icatibant, Bradykinin antagonist, acute attack, subcutaneous

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Georgetown University Hospital, Lombardi Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

Icatibant- Randomized

Placebo-Randomized

Controlled Open-label / laryngeal attack

Untreated Patients at the baseline

Arm Description

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

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

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

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) )

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
November 26, 2004
Last Updated
May 24, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00097695
Brief Title
Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema
Official Title
Randomized, Double Blind, Placebo-Controlled, Multicenter Study of a Subcutaneous Formulation of Icatibant for the Treatment of Hereditary Angioedema
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
December 28, 2004 (Actual)
Primary Completion Date
July 17, 2006 (Actual)
Study Completion Date
July 17, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angioedema
Keywords
Hereditary Angioedema, C1 inhibitor deficiency, HAE, Icatibant, Bradykinin antagonist, acute attack, subcutaneous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Icatibant- Randomized
Arm Type
Experimental
Arm Description
Patients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.
Arm Title
Placebo-Randomized
Arm Type
Placebo Comparator
Arm Description
Patients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack.
Arm Title
Controlled Open-label / laryngeal attack
Arm Type
Experimental
Arm Description
Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.
Arm Title
Untreated Patients at the baseline
Arm Type
Experimental
Arm Description
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) )
Intervention Type
Drug
Intervention Name(s)
Icatibant
Other Intervention Name(s)
Brand name, Firazyr®
Intervention Description
30 mg (3mL) subcutaneous icatibant injection in the abdominal region
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Solution for injection, matched to study drug Single dose: 3 mL
Primary Outcome Measure Information:
Title
Time to Onset of Symptom Relief (TOSR)
Description
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.
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Time to Regression (Start of Improvement) According to Patient
Description
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 Frame
5 days
Title
Time to Almost Complete Symptom Relief
Description
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.
Time Frame
5 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Georgetown University Hospital, Lombardi Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007-2197
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24749847
Citation
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.
Results Reference
derived
PubMed Identifier
20818888
Citation
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. Erratum In: N Engl J Med. 2010 Oct 7;363(15):1486.
Results Reference
derived

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Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema

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