35
Berinert
®
and placebo were administered by slow intra-
venous infusion (recommended 4 mL per minute) within
5 hours of an attack.
As illustrated in Figure 14, if a patient did not experience the
onset of relief of symptoms within 4 hours after infusion,
investigators had the option to administer a second infusion
of blinded study medication:
•
Group 1: Placebo for the 20 IU/kg group
•
Group 2: 10 IU/kg Berinert
®
for the 10 IU/kg group
•
Group 3: 20 IU/kg Berinert
®
for the placebo group.
In the rare case that a patient developed life-threatening
laryngeal edema after inclusion into the study, immediate
start of open-label treatment with a 20 IU/kg body weight
dose of Berinert
®
(and inclusion into I.M.P.A.C.T.2) was
allowed.
Efficacy
5.1 Study Design of the I.M.P.A.C.T. Trials
5.11 I.M.P.A.C.T.1 – Prospective, Multinational,
Randomized, Double-blind Study
78
I.M.P.A.C.T.1 was a prospective, multinational, randomized,
parallel-group, placebo-controlled, dose-finding, 3-arm,
double-blind clinical study to assess the efficacy and safety
of Berinert
®
. A total of 124 adult and pediatric patients with
C1-INH deficiency were included, who were experiencing
a moderate to severe acute attack of abdominal or facial
HAE. Patients were 6 to 72 years of age; 68%were female
and 32%were male. Approximately 90%were Caucasian.
Primary Endpoint
The primary endpoint for efficacy was:
•
Patient-reported time from start of treatment with
Berinert
®
to onset of symptom relief.
Time to onset of symptom relief has been retrospectively
validated by correlation with the course of HAE symp-
toms.
79
Secondary Endpoints
The secondary endpoints for efficacy were:
•
Proportion of patients with worsened intensity of
symptoms between 2 and 4 hours after treatment
compared to baseline
•
Number of vomiting episodes within 4 hours after
treatment with Berinert
®
•
Patient-reported time to complete resolution of all
HAE symptoms, including pain.
Randomized Patient Groups and Dosing
Patients were randomized to receive a single dose of one
of the following:
•
Group 1: 20 IU/kg body weight dose of Berinert
®
(43 patients)
•
Group 2: 10 IU/kg body weight dose of Berinert
®
(39 patients)
•
Group 3: Placebo (42 patients).
Figure 14 – Phase III Prospective, Multinational,
Randomized, Parallel-group, Placebo-controlled,
Dose-finding, Double-blind I.M.P.A.C.T.1
Study Design
Group 2
Group 3
Group 1
Initial Berinert
®
Dose
If No Relief
in 4 h
20 IU/kg
Placebo
10 IU/kg
10 IU/kg
Placebo
20 IU/kg
