Human C1 Esterase Inhibitor (C1-INH) in Subjects With Acute Abdominal or Facial Hereditary Angioedema (HAE) Attacks

Human C1 Esterase Inhibitor (C1-INH) in Subjects With Acute Abdominal or Facial Hereditary Angioedema (HAE) Attacks

Human Pasteurized C1 Esterase Inhibitor Concentrate (CE1145) in Subjects With Congenital C1-INH Deficiency and Acute Abdominal or Facial HAE Attacks

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.

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.

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

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

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.

Includes any worsening of intensity of at least 1 of the HAE symptoms present at baseline. Routinely checked symptoms included pain, nausea, vomiting, cramps, and diarrhea.

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

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.

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.

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.

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. Erratum In: Ann Allergy Asthma Immunol. 2011 Jan;106(1):78.

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