NCT00912093

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

Completed Phase 3 Results posted Last updated 11 June 2021

What this trial tests

Phase 3 trial testing Icatibant in Hereditary Angioedema in 98 participants. Completed in 1 October 2010.

Timeline

16 July 2009

Primary endpoint
1 October 2010

1 October 2010

Quick facts

Lead sponsor	Shire
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	98
Start date	16 July 2009
Primary completion	1 October 2010
Estimated completion	1 October 2010
Sites	64 locations across South Africa, Russia, Ukraine, Israel, Hungary, Romania, Canada, Australia

Drugs / interventions tested

• Icatibant (ICATIBANT) — full drug profile →
• Placebo

Conditions studied

• Hereditary Angioedema — all drugs for Hereditary Angioedema →

Sponsor

Shire — full company profile →

Who can join

18 and older, any sex, with Hereditary Angioedema. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient Primary · 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 observat

Group	Value	95% CI
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	2.0	1.5 – 3.0
Randomized-Placebo (Blinded Treatment)-Non-laryngeal	19.8	6.1 – 26.3

Time to Onset of Primary Symptom Relief Secondary · 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.

Group	Value	95% CI
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	1.5	1.0 – 2.0
Randomized-Placebo (Blinded Treatment)-Non-laryngeal	18.5	3.6 – 23.9

Time to Almost Complete Symptom Relief Secondary · 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.

Group	Value	95% CI
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	8.0	5.0 – 42.5
Randomized-Placebo (Blinded Treatment)-Non-laryngeal	36.0	29.0 – 50.9

Time to Subject-Assessed Initial Symptom Improvement Secondary · 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.

Group	Value	95% CI
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	0.8	0.5 – 1.0
Randomized-Placebo (Blinded Treatment)-Non-laryngeal	3.5	1.9 – 5.4

Time to Investigator-Assessed Initial Symptom Improvement Secondary · 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.

Group	Value	95% CI
Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	0.8	0.6 – 1.3
Randomized-Placebo (Blinded Treatment)-Non-laryngeal	3.4	2.6 – 6.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment emergent adverse events occurring within 16 days of study drug administration are included in the analysis. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Controlled Phase - Icatibant (Randomized)

Serious: 0/46 (0%)

Deaths: —

Controlled Phase -Placebo (Randomized)

Serious: 5/46 (11%)

Deaths: —

Controlled Phase - Icatibant (Open Label)

Serious: 0/6 (0%)

Deaths: —

Open Label Extension - Icatibant (Open Label)

Serious: 7/82 (9%)

Deaths: —

Serious adverse events (9 terms)

Reaction	System	Controlled Phase - Icatiba…	Controlled Phase -Placebo …	Controlled Phase - Icatiba…	Open Label Extension - Ica…
Hereditary angioedema	Congenital, familial and genetic disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—
Tracheostomy	Surgical and medical procedures	—	—	—	—
Arrhythmia	Cardiac disorders	—	—	—	—
Non-Cardiac Chest Pain	General disorders	—	—	—	—
Pneumonia	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Controlled Phase - Icatiba…	Controlled Phase -Placebo …	Controlled Phase - Icatiba…	Open Label Extension - Ica…
Hereditary angioedema	Congenital, familial and genetic disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—	—	—

Most-reported serious reactions: Hereditary angioedema, Myocardial infarction, Gastroenteritis, Tracheostomy, Arrhythmia, Non-Cardiac Chest Pain, Pneumonia, Pulmonary Embolism.

Data from ClinicalTrials.gov NCT00912093 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Randomized placebo-controlled trial of the bradykinin B₂ receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial.
   Lumry WR, Li HH, Levy RJ, Potter PC, et al · · 2011 · cited 160× · PMID 22123383 · DOI 10.1016/j.anai.2011.08.015
2. Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3.
   Lumry WR, Farkas H, Moldovan D, Toubi E, et al · · 2015 · cited 25× · PMID 26556097 · DOI 10.1159/000441060
3. Treatment of hereditary angioedema with icatibant: efficacy in clinical trials versus effectiveness in the real-world setting.
   Maurer M, Longhurst HJ, Fabien V, Li HH, et al · · 2014 · cited 21× · PMID 25198193 · DOI 10.2500/aap.2014.35.3780
4. Clinical efficacy of icatibant in the treatment of acute hereditary angioedema during the FAST-3 trial.
   Baş M. · · 2012 · cited 18× · PMID 23167682 · DOI 10.1586/eci.12.67
5. Rare disease patients in India are rarely involved in international orphan drug trials.
   Chakraborty M, Choudhury MC, Chakraborty I, Saberwal G. · · 2022 · cited 9× · PMID 36962798 · DOI 10.1371/journal.pgph.0000890
6. Abstracts from the European Academy of Allergy and Clinical Immunology Congress, 7-11 June, 2014, Copenhagen, Denmark.
   · 2014 · cited 1× · PMID 25155177 · DOI 10.1111/all.12491
7. Poster Session Group III
   · 2014
8. Analysis of icatibant for the treatment of laryngeal hereditary angioedema attacks in the FAST-3 study
   Yang W, Hébert J, Ritchie B, Baptista J, et al · · 2014 · DOI 10.1186/1710-1492-10-s2-a51