Clinical Trial: A Study of Icatibant in Patients With Acute Attacks of Hereditary Angioedema (FAST-3)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase III Randomized, Double-Blind,Placebo-Controlled, Multicenter Study of Icatibant for Subcutaneous Injection in Patients With Acute Attacks of Hereditary Angioedema

Brief Summary: This study is being conducted to evaluate the efficacy and safety of icatibant compared to placebo in patients experiencing acute attacks of hereditary angioedema (HAE).

Detailed Summary:

This Phase 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 and safety of icatibant compared with placebo for the first treated cutaneous and/or abdominal attack.

Patients with moderate to severe abdominal or cutaneous attacks were randomized to receive a single, blinded, subcutaneous injection of icatibant (30 mg) or placebo. After a protocol amendment, patients with mild to moderate laryngeal HAE attacks were also randomized to receive a single, blinded subcutaneous injection of icatibant (30 mg) or placebo in order to obtain blinded, controlled efficacy and safety data for this subset of subjects. Patients experiencing severe laryngeal attacks (post-amendment) or mild to severe laryngeal attacks (pre-amendment) were to receive open-label icatibant.

After treatment of the first attack in the controlled phase, 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 study was discontinued or the product was commercially available.


Sponsor: Shire

Current Primary Outcome: Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient [ Time Frame: Up to 120 hours post-dose ]

Time to onset of symptom relief was calculated from study drug administration to onset of symptom relief, where onset of symptom relief was defined as the earliest of 3 consecutive measurements in which there was a 50% reduction from pretreatment in composite VAS score. Composite VAS score comprised 3 symptoms, including skin swelling, skin pain, and abdominal pain, for cutaneous and abdominal attacks and 5 symptoms, including skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change, for laryngeal attacks. Subjects who did not achieve symptom relief within the observation period were censored at the last observation time.


Original Primary Outcome: Time to symptom relief for an acute attack, as assessed by the patient [ Time Frame: Patients monitored for 8 hrs or until stable ]

Current Secondary Outcome:

  • Time to Onset of Primary Symptom Relief [ Time Frame: Up to 120 hours post-dose ]
    Time to primary symptom relief was calculated from the time of study drug administration to the onset of primary symptom relief, where onset of primary symptom relief was determined using the subject-assessed VAS score for a single primary symptom (determined by edema location) and defined as the earliest of 3 consecutive non-missing measurements in which a pre-specified reduction from the pretreatment value was met. Subjects who did not achieve primary symptom relief within the observation period were censored at the last observation time.
  • Time to Almost Complete Symptom Relief [ Time Frame: Up to 120 Hours post treatment ]
    Time to almost complete symptom relief was calculated from the time of study drug administration to almost complete symptom relief, where almost complete symptom relief was defined as the earliest of 3 consecutive non-missing measurements in which all VAS scores <10 mm. Subjects who did not achieve almost complete symptom relief within the observation period were censored at the last observation time.
  • Time to Subject-Assessed Initial Symptom Improvement [ Time Frame: Up to 120 hours post-dose ]
    Time to initial symptom improvement was calculated from the time of study drug administration to initial symptom improvement as determined by the subject as the time they felt symptoms were starting to improve. Subjects who did not achieve initial symptom improvement within the observation period were censored at the last observation time.
  • Time to Investigator-Assessed Initial Symptom Improvement [ Time Frame: Up to 120 hours post-dose ]
    Time to initial symptom improvement was calculated from the time of study drug administration to initial symptom improvement as determined by the investigator as the time they felt symptoms were starting to improve. Subjects who did not achieve initial symptom improvement within the observation period were censored at the last observation time.


Original Secondary Outcome:

  • Change in VAS score from pretreatment [ Time Frame: 4 and 8 hours post-treatment ]
  • Evaluation of global outcome of treatment using symptom severity score (by patient and investigator) [ Time Frame: Up to 12 hours post-treatment ]
  • Assessment of global improvement(by patient and investigator) [ Time Frame: 4 and 8 hours post-treatment ]
  • Global assessment of symptoms (by investigator) [ Time Frame: 4 and 8 hours post-treatment ]
  • Time(s) to initial symptom improvement and almost complete symptom relief [ Time Frame: Up to 5 days post-treatment ]
  • Safety and tolerability [ Time Frame: Up to 14 days post-treatment ]
  • Time to reduction in symptom severity of laryngeal attacks [ Time Frame: Up to Day 5 post-treatment ]


Information By: Shire

Dates:
Date Received: June 2, 2009
Date Started: June 2009
Date Completion:
Last Updated: September 11, 2014
Last Verified: July 2014