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The results from the Phase III, double blind, placebo-controlled trialI.M.P.A.C.T. (International Multi-centre Prospective Angioedema C1-inhibitorTrial), showed that patients treated with 20 U/kg b.w. C1-INH experienced ahighly significant reduction in time to onset of relief of symptoms of HAEattacks compared to placebo (p= 0.003, one sided). In addition, all secondaryendpoints of the trial have shown significant positive results, e.g. worseningof symptoms (p= 0.001, one sided).
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"The results of this trial can immediately impact the lives of thethousands of HAE patients around the world who live with the burden of acuteHAE attacks without approved treatment," said Timothy Craig, M.D., professorof medicine and pediatrics, Penn State Hershey Medical Center, USA,coordinating investigator of the I.M.P.A.C.T. trial.
I.M.P.A.C.T. is a multi-center, prospective clinical trial conductedglobally in more than 45 centers in 15 countries, enrolling 125 patients, andis the largest trial ever conducted in HAE. For the first time, a dosecomparison study was conducted for a human C1-INH comparing 20U/ kg b.w. and10U/ kg b.w. in a randomized, placebo-controlled, double-blind study design.The results will be submitted in the near future to the United States Food andDrug Administration, Health Canada and European Health Authorities in supportof applications to license C1-INH concentrate for the treatment of acuteattacks of HAE in the U.S., Canada, and Europe. CSL Behring has manufacturedand provided C1-INH concentrate to HAE patients for over 20 years in Germany,Austria, Switzerland, and several other countries, where it is licensed underthe trade name Berinert(R) P for the treatment of acute HAE attacks.
"The successful completion of this trial confirms longstandingobservations made from the administration of more than 300,000 treatments ofC1-INH concentrate in Europe. We are delighted that it will now be submittedfor registration in the UK," said Dr. Hilary Longhurst, ConsultantImmunologist, Barts and The London NHS Trust, London, England, andinvestigator of the I.M.P.A.C.T. trial.
Study design and results
HAE is caused by the partial absence of functional C1 inhibitor in theblood. The objective of I.M.P.A.C.T. was to assess whether replacing the C1protein missing in patients with HAE through treatment with C1-INH can addressthe underlying mechanism of the disease.
I.M.P.A.C.T. evaluated in a prospective and double-blind fashion whetherdifferent doses of human pasteurized C1-INH concentrate lead to faster reliefof acute symptoms of abdominal and facial attacks compared with placebo inpatients with HAE. It is also the largest dose comparison study ever done inHAE. To be eligible for inclusion in the study, patients had to be six yearsof age or older, with a diagnosis of C1-INH deficiency and a documentedhistory of facial or abdominal attacks.
The primary objective was to show that C1-INH shortens the time to onsetof relief of symptoms of abdominal or facial HAE attacks. The primaryendpoint was time between start of C1-INH administration and onset of reliefof symptoms from abdominal or facial attacks as determined by the subject'sassessment. The median time to onset of relief of symptoms in the 20 U/kg b.w.C1-INH treatment group was 30 minutes, compared to 1.5 hours for patients whoreceived placebo.
The secondary endpoint, that is, the proportion of subjects with increasedintensity of clinical HAE symptoms between two and four ho
