This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase II study to further demonstrate the safety of rhC1INH as well as assess the efficacy of rhC1INH at doses of 50 and 100 U/kg in relieving eligible attacks of angioedema with involvement of submucosal tissues in patients with HAE. This study is intended to be part of a larger study, pending the outcome of the formal analysis of safety and efficacy. Upon review of the clinical study report, an amendment may be submitted to the regulatory agencies to expand the sample of randomized treatments and to explore open-label treatments at a dose to be determined. Patients who have qualified for enrollment in advance and who present to a study center within 5 hours of onset of an attack of angioedema localized in the abdomen (presumed gastrointestinal tract), facial-oropharyngeal-laryngeal region, and/or urogenital region ('submucosal' attacks) will be evaluated for eligibility by the investigators. An attack will be eligible if the patient presents with at least one eligible ('submucosal') location of angioedema. A location will be considered 'eligible' if the patient's VAS score for overall symptom severity at this location at evaluation is at least 50 mm, where 0 mm means 'no symptoms at all' and 100 mm means 'extremely disabling'. Thirty-nine eligible patients will be randomized (1:1:1) to receive an intravenous infusion of rhC1INH at 100 U/kg, rhC1INH at 50 U/kg or placebo in a double-blind fashion. Randomization will be central and occur immediately after an eligible patient has been reported. After treatment, subjects will be monitored for response (Visual analogue scale for pain and symptoms, symptom questionnaire) and safety ( Vital signs, ECG, adverse events, immunogenicity, routine laboratory analyses) for the next 12 hours. Pharmacokinetic blood samples will be drawn after the treatment. Three daily follow-up visits and two delayed visits will review the long-term safety and tolerability of this agent.
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