The study hypothesis is that treatment of Hereditary Angioedema at the time of prodromal
      symptoms will decrease morbidity associated with the disease

C1-INH Compared to Placebo at the Time of Prodromal Symptoms for Hereditary Angioedema (HAE) Exacerbation

Hereditary Angioedema

Section 3 Study Design and Methods:

      Our proposal is to perform a randomized double-blind, three-arm, three-way cross-over study
      in which subjects with HAE would be placed into one of three different treatment groups based
      on computer randomization. Subjects will be randomized to receive placebo, 1000 units, or
      1500 units of C1-INH at the onset of prodromal symptoms although they would be blinded to
      which one they were receiving. Randomization will be to one of the two doses or placebo and
      the sequence of further treatments will be determined randomly in a double-blinded fashion by
      a person who is not involved in the study. The randomized drug will be available 24 hours and
      7 days a week. They would have to come to the study office to receive the blinded drug, and
      would need to seek treatment within 6 hours of the onset of the prodrome. Following the
      blinded treatment, the subject would need to be observed for at least 30 minutes. If a
      subject develops an acute HAE exacerbation in any of the three treatment periods, they would
      have access to 20 units/kg of open label C1-INH for acute treatment also received at the
      study office, and the time from onset of symptoms of an acute attack until the time the
      subject sought open-label treatment could not exceed 12 hours. Following open label rescue,
      the subject would need to be observed for at least 1 hour or until symptoms started to
      improve. The subject would also be expected to complete a symptom diary card over the next 24
      hours after receiving open-label C1-INH to monitor severity and duration of symptoms (24 Hour
      Prodrome/Open-Label Diary Appendix IV) associated with the acute attack. The number,
      duration, and severity of acute HAE attacks would be compared for each treatment period. Each
      treatment period would last 16 weeks so each subject would be studied for a total of 48
      weeks. Because safety has been established when C1-INH is used every third day with
      prophylaxis therapy, and patients may receive C1-INH for an attack without limits on the
      closeness of the attacks, our patients in this study may be retreated for prodromal symptoms
      as they require it, but not more than every other day since prodromes may precede the
      swelling and abdominal pain by up to 2 days.

      Thrombosis has been identified with C1-INH, but only in neonates who were premature and at
      much higher doses than 1500 units every third day. Cinryze, also a C1-INH, is FDA approved
      for 1000 units every third day for prophylaxis. The dosing used in our study reflects the FDA
      approval dosing for Berinert, which is 20 units per kg for acute therapy, so that most
      patients will receive 1000 to 2500 units of C1-inh whenever they have an attack without day
      restrictions between dosing. The dosage approved by the FDA is 20 units per kg for Berinert
      and 1000 units total dose for Cinryze. The dose used in our study approximates these doses,
      but is not an FDA approved dose. There are no limits on how often Berinert can be dosed for
      acute attacks.

      Figure IV outlines our treatment protocol.

      Figure IV: Three-arm, randomized, cross-over, double-blind, placebo-controlled trial to
      determine effect of treating prodromal symptoms with C1-INH infusions of 1000 units, or 1500
      units versus placebo. The sequence is random and double-blinded.

C-1-esterase

placebo

Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Determine the Efficacy of 1000u, and 1500u of C1-INH Compared to Placebo at the Time of Prodromal Symptoms in Preventing an Acute HAE Exacerbation.

To compare the percentage of full blown HAE attacks occurring within 24 hours following treatment at the prodromal stage of an attack using placebo or one of two doses of C1-INH.

Principal Investigator

1000 units of C-1-esterase inhibitor given at time of prodromal symptoms

treatment with 1500 units of C-1-esterase inhibitor IV at the time of prodromal symptoms to decrease risk of exacerbation of HAE

placebo injection given for prodromal symptoms as double blinded therapy

C1-INH Compared to Placebo at the Time of Prodromal Symptoms for Hereditary Angioedema (HAE) Exacerbation

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?