36
100
90
80
70
60
50
40
30
20
10
0
0
1
2
3
4
5
6
% of Patients
Time to Onset of Symptom Relief (hours)
Time to Onset of Symptom Relief
as Determined by Patients’ Assessment
a
Berinert
®
20 IU/kg Body Weight (n=43)
Berinert
®
10 IU/kg Body Weight (n=39)
Placebo (n=42)
a
Actual values recorded (i.e., values not set to 24 hours if rescue medication was taken).
Figure 15 – Kaplan-Meier Curve for Time to
Onset of Symptom Relief, as Determined by
Patients’ Assessment in I.M.P.A.C.T.1
78
5.2 Proven Efficacy of Berinert
®
in I.M.P.A.C.T.1
78
5.12 I.M.P.A.C.T.2 – Extension Study
80
Berinert
®
was also evaluated in I.M.P.A.C.T.2, a pro-
spective, open-label, uncontrolled, multicenter extension
study conducted at 15 centers in the United States that had
participated in the pivotal study.
The purpose of this extension study was to evaluate
the efficacy and safety of long-term treatment with
20 IU/kg body weight Berinert
®
for angioedema attacks at
any body location.
Primary and Secondary Endpoints
As in I.M.P.A.C.T.1, the primary endpoint in I.M.P.A.C.T.2
was the patient-reported time to onset of symptom
relief, and the secondary endpoint was time to complete
resolution of HAE symptoms.
5.21 Fast Onset of Relief From Pain and Swelling
I.M.P.A.C.T.1 demonstrated that Berinert
®
provided fast
onset of symptom relief (Figure 15).
Moreover, it established the efficacy of a 20 IU/kg dose
of Berinert
®
compared to a 10 IU/kg dose or placebo in
reducing the time to onset of relief from symptoms of an
HAE attack (abdominal or facial) as determined by the
patient’s assessment.
Only 1 hour after treatment with 20 IU/kg, approximately
70% of patients had reported onset of symptom relief
(approximately 40%after treatment with placebo); 4 hours
after treatment, onset of symptom relief was reported by
86% of patients (62% after treatment with placebo).
80
Due to insufficient or no symptom relief 4 hours after
initial treatment, 45 (36%) patients received a blinded
second dose of study medication (placebo or Berinert
®
).
The percentage of patients was considerably lower with
20 IU/kg Berinert
®
(19%) than with 10 IU/kg (33%) and
placebo (57%). After administration of this second dose,
the median time to onset of symptom relief was 0.5 hours.
Patient Groups and Dosing
Patients were eligible for I.M.P.A.C.T.2 if they had previously
participated in I.M.P.A.C.T.1 and had any type of HAE
attack. Patients eligible for I.M.P.A.C.T.1 who suffered from
a laryngeal attack were directly enrolled in I.M.P.A.C.T.2.
After enrollment, patients received a 20 IU/kg body weight
dose of Berinert
®
for each attack and were observed at the
study site until the onset of HAE symptom relief.
A total of 57 patients (19 males and 38 females; age range:
10 to 53 years) with 1,085 HAE attacks were evaluated.
There were 51 patients with abdominal attacks, 30 patients
with peripheral attacks, 21 patients with facial attacks, and
16 patients with laryngeal attacks.
