Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema

NCT00262301 | Completed Phase 3 Results DMC

• 1 other identifier: C1 1304-01
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 2

Brief Summary

Hereditary angioedema ("HAE") is a genetic disorder characterized by sudden recurrent attacks of local swelling (angioedema). These attacks are often painful and disabling, and, in some cases, life-threatening. "HAE" is caused by mutations in the "C1INH" gene that leads to a decrease in the blood level of functional "C1INH". This multi-center study was designed to assess the safety and tolerability, efficacy and pharmacodynamics/ pharmacokinetics of recombinant human C1 inhibitor ("rhC1INH") in the treatment of acute hereditary angioedema attacks.

Conditions

Hereditary Angioedema; Angioneurotic Edema; Genetic Disorders

Outcome Measures

Primary Outcomes (1)

• Time to Beginning of Relief of Symptoms

  The time to beginning of relief of symptoms has been assessed by using a patient-reported visual analogue scale ("VAS") ranging from 0 mm (no symptoms at all) to 100 mm (extremely disabling). Time to beginning of relief of symptoms at the location that showed first "VAS" score decrease of at least 20 mm from baseline score (t= 0 min) to the next assessment time-point). Assessment time-points were taken on pre-scheduled time-points after drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to beginning of relief has been calculated as median time, by using the exact time-points on which each assessment was performed.

  up to 48 hours after study drug administration

Secondary Outcomes (1)

• Time to Minimal Symptoms

  up to 48 hours after study drug administration

Study Arms (2)

100 IU/kg "rhC1INH"

EXPERIMENTAL

100 IU/kg recombinant human C1 inhibitor

Drug: recombinant human C1 inhibitor

Saline

PLACEBO COMPARATOR

Saline solution

Drug: Placebo

Interventions

recombinant human C1 inhibitor DRUG

IV

Also known as: "rhC1INH", Ruconest, conestat alfa

100 IU/kg "rhC1INH"

Placebo DRUG

IV

Also known as: saline, physiological salt solution

Saline

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clear clinical and laboratory diagnosis of HAE
• Baseline plasma level of functional C1INH of less than 50% of normal
• Evidence for exacerbation or development of a severe abdominal, oro-facial/ pharyngeal/ laryngeal, genito-urinary and/or peripheral HAE attack

You may not qualify if:

• Acquired angioedema
• Pregnancy or breastfeeding
• Participation in another clinical study within prior 3 months

Sponsors & Collaborators

• Pharming Technologies B.V.: lead

Study Sites (2)

For information on sites, please contact Pharming Medical Affairs Deparment

Leiden, 2300 AL, Netherlands

Location

Emergency County Hospital, Internal Medicin Clinica, Allergology-Immunology Department

Târgu Mureş, 541103, Romania

Location

Related Publications (3)

• Zuraw B, Cicardi M, Levy RJ, Nuijens JH, Relan A, Visscher S, Haase G, Kaufman L, Hack CE. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol. 2010 Oct;126(4):821-827.e14. doi: 10.1016/j.jaci.2010.07.021.

  PMID: 20920772 RESULT

• Moldovan D, Reshef A, Fabiani J, Kivity S, Toubi E, Shlesinger M, Triggiani M, Montinaro V, Cillari E, Realdi G, Cancian M, Visscher S, Zanichelli A, Relan A, Cicardi M. Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study. Clin Exp Allergy. 2012 Jun;42(6):929-35. doi: 10.1111/j.1365-2222.2012.03984.x.

  PMID: 22909164 RESULT

• Bernstein JA, Relan A, Harper JR, Riedl M. Sustained response of recombinant human C1 esterase inhibitor for acute treatment of hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2017 Apr;118(4):452-455. doi: 10.1016/j.anai.2017.01.029. Epub 2017 Mar 9.

  PMID: 28284978 DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary; Angioedema; Genetic Diseases, Inborn

Interventions

Complement C1 Inhibitor Protein; conestat alfa; Sodium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Medical Affairs Department
• Organization: Pharming Technologies BV

medicalinfo@pharming.com

+31715247400

Study Officials

• Jan Nuijens, MD, PhD

  Pharming Group N.V.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2005
• First Posted: December 6, 2005
• Study Start: June 1, 2004
• Primary Completion: July 1, 2009
• Study Completion: October 1, 2009
• Last Updated: October 2, 2012
• Results First Posted: August 30, 2012

Record last verified: 2012-09

Locations

NL (1); RO (1)