C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks

NCT ID: NCT00289211

Last Updated: 2021-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-14
• Study Completion Date: 2007-04-13

Brief Summary

The study objective was to determine the safety and efficacy of C1INH-nf for the treatment of acute HAE attacks.

Detailed Description

Randomized subjects treated for a qualifying attack were eligible to receive rescue dosing with 1,000 U of C1INH-nf if they did not achieve beginning of substantial relief of the defining symptom within 4 hours after initial treatment with blinded study drug, or if at any time the attack progressed to include airway compromise. A second 1,000 U rescue dose was permitted 60 minutes after the initial rescue dose, if necessary.

The study design also allowed for administration of open-label C1INH-nf for laryngeal angioedema attacks, which were non-randomizable events due to the presence of or potential for airway compromise (immediate 1,000 U dose of C1INH-nf, repeated after 60 minutes, if necessary). In addition, subjects were eligible to receive open-label C1INH-nf (1,000 U single dose) prior to emergency surgical (non-cosmetic) procedures.

A total of 83 subjects were enrolled in the study. Seventy-one (71) subjects experienced qualifying attacks and were randomized to blinded study drug (36 C1INH-nf, 35 placebo); only the 71 randomized subjects were analyzed for efficacy. An additional 12 subjects were never randomized but received open-label C1INH-nf for treatment of laryngeal angioedema and/or prior to emergency surgical procedures. Of the 35 subjects randomized to placebo, 23 also received C1INH-nf (eg, rescue, open-label). In total, 83 subjects received at least 1 dose of study drug and were analyzed for safety; 71 subjects were exposed to C1INH-nf (59 randomized, 12 open-label only) and 12 subjects were exposed only to placebo.

Conditions

Hereditary Angioedema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

C1INH-nf

1,000 Units (U) of C1INH-nf administered intravenously (IV). If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.

Group Type: EXPERIMENTAL

C1 esterase inhibitor [human] (C1INH-nf)

Intervention Type: BIOLOGICAL

Placebo

Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered.

Group Type: PLACEBO_COMPARATOR

Placebo (saline)

Intervention Type: DRUG

Interventions

C1 esterase inhibitor [human] (C1INH-nf)

Intervention Type: BIOLOGICAL

Placebo (saline)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Documented HAE
• Normal C1q level

Exclusion Criteria

• Low C1q level
• B-cell malignancy
• Presence of anti-C1INH autoantibody
• History of allergic reaction to C1INH or other blood products
• Narcotic addiction
• Current participation in any other investigational drug study or within the past 30 days
• Participation in a C1 esterase inhibitor trial, or received blood or a blood product in the past 90 days
• Pregnancy or lactation
• Any clinically significant medical condition, such as renal failure, that in the opinion of the investigator would interfere with the subject's ability to participate in the study

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Clinical Research Consultants, Inc

Hoover, Alabama, United States

Allergy and Immunology Associates

Scottsdale, Arizona, United States

UCLA-David Geffen School of Medicine

Los Angeles, California, United States

University of California, San Diego

San Diego, California, United States

Allergy and Asthma Clinical Research, Inc

Walnut Creek, California, United States

Allergy and Asthma Center

Fort Lauderdale, Florida, United States

Orlando Regional Healthcare

Orlando, Florida, United States

Family Allergy and Asthma Center

Atlanta, Georgia, United States

Welborn Clinic Allergy and Immunology

Evansville, Indiana, United States

University of Iowa Hospital and Clinic

Iowa City, Iowa, United States

The Baton Rouge Clinic, AMC

Baton Rouge, Louisiana, United States

Institute for Asthma and Allergy

Wheaton, Maryland, United States

Allergy Asthma and Immunology

Falmouth, Massachusetts, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Grand Traverse Allergy

Traverse City, Michigan, United States

St. Louis University School of Medicine

St Louis, Missouri, United States

Nevada Access to Research and Education Society

Las Vegas, Nevada, United States

UMDNJ Asthma and Allergy Research Center

Newark, New Jersey, United States

Winthrop University Hospital

Mineola, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

MeritCare Clinical Research

Fargo, North Dakota, United States

Bernstein Clinical Research

Cincinnati, Ohio, United States

Optimed Research

Columbus, Ohio, United States

Allergy Clinic of Tulsa

Tulsa, Oklahoma, United States

Allergy Asthma and Dermatology Research Center

Lake Oswego, Oregon, United States

Penn State University

Hershey, Pennsylvania, United States

Allergy Partners of the Upstate

Greenville, South Carolina, United States

AARA Research Center

Dallas, Texas, United States

University of Texas Medical Branch

Galveston, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Allergy and Asthma Research Center

San Antonio, Texas, United States

Virginia Adult and Pediatric Allergy and Asthma

Richmond, Virginia, United States

Marycliff Allergy Specialists

Spokane, Washington, United States

Puget Sound Allergy, Asthma and Immunology

Tacoma, Washington, United States

Allergy, Asthma and Pulmonary Clinical Research

Madison, Wisconsin, United States

Countries

United States

References

Lumry W, Manning ME, Hurewitz DS, Davis-Lorton M, Fitts D, Kalfus IN, Uknis ME. Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr. 2013 May;162(5):1017-22.e1-2. doi: 10.1016/j.jpeds.2012.11.030. Epub 2013 Jan 11.

Reference Type: DERIVED

PMID: 23312695 (View on PubMed)

Grant JA, White MV, Li HH, Fitts D, Kalfus IN, Uknis ME, Lumry WR. Preprocedural administration of nanofiltered C1 esterase inhibitor to prevent hereditary angioedema attacks. Allergy Asthma Proc. 2012 Jul-Aug;33(4):348-53. doi: 10.2500/aap.2012.33.3585.

Reference Type: DERIVED

PMID: 22856635 (View on PubMed)

Zuraw BL, Busse PJ, White M, Jacobs J, Lumry W, Baker J, Craig T, Grant JA, Hurewitz D, Bielory L, Cartwright WE, Koleilat M, Ryan W, Schaefer O, Manning M, Patel P, Bernstein JA, Friedman RA, Wilkinson R, Tanner D, Kohler G, Gunther G, Levy R, McClellan J, Redhead J, Guss D, Heyman E, Blumenstein BA, Kalfus I, Frank MM. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):513-22. doi: 10.1056/NEJMoa0805538.

Reference Type: DERIVED

PMID: 20818886 (View on PubMed)

Other Identifiers

LEVP2005-1/Part A

Identifier Type: -

Identifier Source: org_study_id