MedPath

Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema

Phase 3
Completed
Conditions
Angioedema
Interventions
Drug: Placebo
Registration Number
NCT00097695
Lead Sponsor
Shire
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
84
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Placebo-RandomizedPlaceboPatients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack.
Icatibant- RandomizedIcatibantPatients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.
Controlled Open-label / laryngeal attackIcatibantPatients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.
Untreated Patients at the baselineIcatibantPatients 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) )
Primary Outcome Measures
NameTimeMethod
Time to Onset of Symptom Relief (TOSR)5 days

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
NameTimeMethod
Time to Regression (Start of Improvement) According to Patient5 days

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 Relief5 days

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.

Trial Locations

Locations (1)

Georgetown University Hospital, Lombardi Cancer Center

🇺🇸

Washington, District of Columbia, United States

© Copyright 2025. All Rights Reserved by MedPath