Clinical trial NCT00168103: Human C1 Esterase Inhibitor (C1-INH) in Subjects With Acute Abdominal or Facial Hereditary Angioedema (HAE) Attacks
Official title: Human Pasteurized C1 Esterase Inhibitor Concentrate (CE1145) in Subjects With Congenital C1-INH Deficiency and Acute Abdominal or Facial HAE Attacks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hereditary Angioedema
Keywords: C1 Inhibitor
Hereditary angioedema
Acute HAE attack
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2005-09-14
Enrollment: 126
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: HAE is a rare disorder characterized by functional C1 esterase inhibitor deficiency. If not treated adequately, the acute attacks of HAE can be life-threatening and may even result in fatalities, especially in case of swelling of the larynx. This clinical Phase 2/Phase 3 study was designed to provide clinically relevant data on dosing, efficacy and safety in subjects with HAE.

Detailed description: For each subject, only a single abdominal or facial attack was treated and evaluated. After receiving treatment, subjects were observed for a minimum of 4 hours, after which they could be discharged from the study center if they reported onset of symptom relief. Starting from 4 hours after treatment, subjects who reported insufficient or no symptom relief could receive a second dose of double-blind treatment (called "rescue medication") as follows: C1-INH 20 U/kg bw for subjects initially receiving placebo, C1-INH 10 U/kg bw for subjects initially receiving C1-INH 10 U/kg bw, and placebo for subjects initially receiving C1-INH 20 U/kg bw.

The study was defined to be successful if the primary outcome measure and at least one of the secondary outcome measures were met in the comparison between the C1-INH 20 U/kg bw group and the Placebo group.

Eligibility criteria: Key Inclusion Criteria:

* Documented congenital C1-INH deficiency
* Acute facial or abdominal HAE attack

Key Exclusion Criteria:

* Acquired angioedema
* Treatment with any other investigational drug within the last 30 days before study entry
* Treatment with any C1-INH concentrate within the previous 7 days

Primary outcomes:
measure: Time to Start of Relief of Symptoms From HAE Attack
timeFrame: Up to 24 h after start of study treatment
Secondary outcomes:
measure: Number of Subjects With Worsened Intensity of Clinical HAE Symptoms
timeFrame: Baseline and between 2 and 4 h after start of study treatment
measure: Number of Vomiting Episodes
timeFrame: Within 4 h after start of study treatment
Other outcomes:
measure: Time to Complete Resolution of All HAE Symptoms, Including Pain
timeFrame: Up to 24 h after start of study treatment
measure: Number of Subjects Receiving Rescue Study Medication
timeFrame: Within 4 h after start of study treatment
Locations:
city: Granada Hills
country: United States
facility: Study Site
state: California
city: Weston
country: United States
facility: Study Site
state: Florida
city: Atlanta
country: United States
facility: Study Site
state: Georgia
city: Idaho Falls
country: United States
facility: Study Site
state: Idaho
city: Chicago
country: United States
facility: Study Site
state: Illinois
city: Shreveport
country: United States
facility: Study Site
state: Louisiana
city: Boston
country: United States
facility: Study Site
state: Massachusetts
city: Plymouth
country: United States
facility: Study Site
state: Minnesota
city: Omaha
country: United States
facility: Study Site
state: Nebraska
city: Bronx
country: United States
facility: Study Site
state: New York
city: Cincinnati
country: United States
facility: Study Site
state: Ohio
city: Tulsa
country: United States
facility: Study Site
state: Oklahoma
city: Eugene
country: United States
facility: Study Site
state: Oregon
city: Hershey
country: United States
facility: Study Site
state: Pennsylvania
city: Rapid City
country: United States
facility: Study Site
state: South Dakota
city: Dallas
country: United States
facility: Study Site
state: Texas
city: Bellingham
country: United States
facility: Study Site
state: Washington
city: Buenos Aires
country: Argentina
facility: Study Site
city: Westmead
country: Australia
facility: Study Site
city: Plovdiv
country: Bulgaria
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study Site
city: Edmonton
country: Canada
facility: Study Site
city: Ottawa
country: Canada
facility: Study Site
city: Brno
country: Czech Republic
facility: Study Site
city: Budapest
country: Hungary
facility: Study Site
city: Tel Hashomer
country: Israel
facility: Study Site
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Study Site
city: Grodzisk Mazowiecki
country: Poland
facility: Study Site
city: Krakow
country: Poland
facility: Study Site
city: Tirgu-Mures
country: Romania
facility: Study Site
city: Moscow
country: Russian Federation
facility: Study Site 1
city: Moscow
country: Russian Federation
facility: Study Site 2
city: Moscow
country: Russian Federation
facility: Study Site 3
city: Madrid
country: Spain
facility: Study Site
city: Goeteborg
country: Sweden
facility: Study Site
city: London
country: United Kingdom
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Program Director, Clinical R&D
role: STUDY_DIRECTOR
References:
citation: Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, Obtulowicz K, Reshef A, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Craig TJ. Hereditary angioedema: Validation of the end point time to onset of relief by correlation with symptom intensity. Allergy Asthma Proc. 2011 Jan-Feb;32(1):36-42. doi: 10.2500/aap.2011.32.3404.
citation: Craig TJ, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz D, Obtulowicz K, Reshef A, Ritchie B, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Bernstein JA. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009 Oct;124(4):801-8. doi: 10.1016/j.jaci.2009.07.017. Epub 2009 Sep 19.
citation: Craig TJ, Rojavin MA, Machnig T, Keinecke HO, Bernstein JA. Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013 Sep;111(3):211-5. doi: 10.1016/j.anai.2013.06.021. Epub 2013 Jul 16.
citation: Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, Obtulowicz K, Reshef A, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Schindel F, Craig TJ. Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2010 Aug;105(2):149-54. doi: 10.1016/j.anai.2010.06.005.