NCT00168103

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
126

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2005

Geographic Reach
15 countries

36 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2005

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

September 12, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 14, 2005

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2007

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2007

Completed
2.7 years until next milestone

Results Posted

Study results publicly available

August 24, 2010

Completed
Last Updated

March 31, 2015

Status Verified

February 1, 2011

Enrollment Period

2.3 years

First QC Date

September 12, 2005

Results QC Date

April 21, 2010

Last Update Submit

March 11, 2015

Conditions

Hereditary Angioedema

Keywords

C1 InhibitorHereditary angioedemaAcute HAE attack

Outcome Measures

Primary Outcomes (1)

  • Time to Start of Relief of Symptoms From HAE Attack

    The start of symptom relief was determined by subject self-assessment. Time to start of symptom relief was set to 24 hours if the subject received rescue medication (blinded study medication, narcotic analgesics, antiemetics, open-label C1-INH, or fresh frozen plasma) at any time point after the start of study treatment but before start of relief.

    Up to 24 h after start of study treatment

Secondary Outcomes (2)

  • Number of Subjects With Worsened Intensity of Clinical HAE Symptoms

    Baseline and between 2 and 4 h after start of study treatment

  • Number of Vomiting Episodes

    Within 4 h after start of study treatment

Other Outcomes (2)

  • Time to Complete Resolution of All HAE Symptoms, Including Pain

    Up to 24 h after start of study treatment

  • Number of Subjects Receiving Rescue Study Medication

    Within 4 h after start of study treatment

Study Arms (3)

C1-INH 10 U/kg bw

EXPERIMENTAL

10 Units (U)/kg body weight (bw) dose

Biological: C1 Esterase Inhibitor

C1-INH 20 U/kg bw

EXPERIMENTAL

20 U/kg bw dose

Biological: C1 Esterase Inhibitor

Placebo

PLACEBO COMPARATOR
Biological: Placebo

Interventions

C1 Esterase InhibitorBIOLOGICAL

Single application of C1-INH administered intravenously by slow injection or infusion at a recommended rate of 4mL/min.

Also known as: Berinert, Berinert P, CE1145
C1-INH 10 U/kg bwC1-INH 20 U/kg bw
PlaceboBIOLOGICAL

Single application of physiological saline solution equivalent to the volume calculated for subjects in the C1-INH 20 U/kg bw arm.

Also known as: Physiological saline solution
Placebo

Eligibility Criteria

Age6 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (36)

Study Site

Granada Hills, California, 91344, United States

Location

Study Site

Weston, Florida, 33331, United States

Location

Study Site

Atlanta, Georgia, 30342, United States

Location

Study Site

Idaho Falls, Idaho, 83404, United States

Location

Study Site

Chicago, Illinois, 60612, United States

Location

Study Site

Shreveport, Louisiana, 71130, United States

Location

Study Site

Boston, Massachusetts, 02115, United States

Location

Study Site

Plymouth, Minnesota, 55411, United States

Location

Study Site

Omaha, Nebraska, 68131, United States

Location

Study Site

The Bronx, New York, 10461, United States

Location

Study Site

Cincinnati, Ohio, 45231, United States

Location

Study Site

Tulsa, Oklahoma, 74133, United States

Location

Study Site

Eugene, Oregon, 97401, United States

Location

Study Site

Hershey, Pennsylvania, 17033, United States

Location

Study Site

Rapid City, South Dakota, 57702, United States

Location

Study Site

Dallas, Texas, 75230, United States

Location

Study Site

Bellingham, Washington, 98225, United States

Location

Study Site

Buenos Aires, Argentina

Location

Study Site

Westmead, Australia

Location

Study Site

Plovdiv, Bulgaria

Location

Study Site

Sofia, Bulgaria

Location

Study Site

Edmonton, Canada

Location

Study Site

Ottawa, Canada

Location

Study Site

Brno, Czechia

Location

Study Site

Budapest, Hungary

Location

Study Site

Tel Litwinsky, Israel

Location

Study Site

Skopje, North Macedonia

Location

Study Site

Grodzisk Mazowiecki, Poland

Location

Study Site

Krakow, Poland

Location

Study Site

Târgu Mureş, Romania

Location

Study Site 1

Moscow, Russia

Location

Study Site 2

Moscow, Russia

Location

Study Site 3

Moscow, Russia

Location

Study Site

Madrid, Spain

Location

Study Site

Gothenburg, Sweden

Location

Study Site

London, United Kingdom

Location

Related Publications (4)

  • 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.

    PMID: 21262096BACKGROUND

  • 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.

    PMID: 19767078RESULT

  • 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.

    PMID: 23987198DERIVED

  • 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.

    PMID: 20674826DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

Complement C1 Inhibitor Protein

Condition Hierarchy (Ancestors)

AngioedemaVascular DiseasesCardiovascular DiseasesHereditary Complement Deficiency DiseasesPrimary Immunodeficiency DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesUrticariaSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesHypersensitivity, ImmediateHypersensitivityImmune System DiseasesImmunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

GlycoproteinsGlycoconjugatesCarbohydratesComplement C1 Inactivator ProteinsSerpinsPeptidesAmino Acids, Peptides, and ProteinsComplement Inactivator ProteinsComplement System ProteinsImmunoproteinsBlood ProteinsProteins

Limitations and Caveats

A test for futility of the C1-INH 10 U/kg bw group conducted during a planned interim analysis led to ceasing recruitment for the C1-INH 10 U/kg bw group.

Results Point of Contact

Title
Clinical Program Director
Organization
CSL Behring
clinicaltrials@cslbehring.com
Use email contact

Study Officials

  • Program Director, Clinical R&D

    CSL Behring

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

September 12, 2005

First Posted

September 14, 2005

Study Start

June 1, 2005

Primary Completion

October 1, 2007

Study Completion

December 1, 2007

Last Updated

March 31, 2015

Results First Posted

August 24, 2010

Record last verified: 2011-02

Locations

CZ(1)AR(1)AU(1)SE(1)RO(1)NO(1)IL(1)BU(2)HU(1)PL(2)ES(1)CA(2)GB(1)RU(3)US(17)