44
Because different clinical studies are conducted under
varying conditions, adverse reaction rates observed cannot
be directly compared to rates in other clinical studies and
may not reflect the rates observed in practice.
5.61 Safety in I.M.P.A.C.T.1 and 2
As mentioned earlier, the I.M.P.A.C.T. clinical trial
program of Berinert
®
was the largest clinical trial
program of an HAE treatment ever conducted. Patients
in I.M.P.A.C.T.1 were treated during moderate to severe
attacks of abdominal or facial swelling and were
randomly assigned to 3 treatment groups as shown on
page 35. Patients in I.M.P.A.C.T.2 were treated with
20 IU/kg Berinert
®
during mild, moderate, or severe attacks
at all body locations.
Table 11 summarizes the adverse events (AEs) that occurred
in I.M.P.A.C.T.1 and 2. AEs that were possibly related to the
study treatment occurred in 10.9%and 14.0%of patients in
I.M.P.A.C.T.1 and 2, respectively, and in 0.8% of all attacks
in I.M.P.A.C.T.2. None of these were serious AEs and only
1 patient discontinued use due to a possibly related AE
which was an infusion related reaction 2 minutes after the
start of infusion. It resolved after 4.6 hours and could not
be clearly defined as allergic or anaphylactoid.
The most commonly reported AEs included headache,
nausea, and nasopharyngitis (Table 12).
Only limited data are available on the occurrence of
autoantibodies toC1-INH inpatientswithHAE after treatment
with C1-INH concentrate. Results from I.M.P.A.C.T.1 and 2
suggest that treatment with Berinert
®
is not associated with
the development of inhibitory anti-C1-INH antibodies.
80
Repeated treatment with Berinert
®
in I.M.P.A.C.T.2 did
not lead to the development of inhibitory anti-C1-INH
antibodies.
81
5.6 Low Rate of Adverse Events and
a Favorable Safety Profile
Type of AE
I.M.P.A.C.T.1
a
I.M.P.A.C.T.2
Number (%)
of Patients
n=46
Number (%)
of Patients
n=57
Number (%)
of Attacks
n=1,085
Any AE
9 (19.6%)
25 (43.9%)
59 (5.4%)
AE possibly related
to study drug
5 (10.9%)
8 (14.0%)
9 (0.8%)
Serious AEs
0
1 (1.8%)
b
1 (<0.1%)
Medication permanently
discontinued due to
possibly related AE
0
1 (1.8%)
c
1 (<0.1%)
System Organ Class/
Preferred Term
I.M.P.A.C.T.1
a
I.M.P.A.C.T.2
Number (%)
of Patients
n=46
Number (%)
of Patients
n=57
Number (%)
of Attacks
n=1,085
Patients with at least 1 AE 10 (21.7%)
25 (43.9%)
59 (5.4%)
Gastrointestinal Disorders
5 (10.9%)
6 (10.5%)
16 (1.5%)
Nausea
3 (6.5%)
1 (1.8%)
7 (0.6%)
Infections and Infestations
0
10 (17.5%)
21 (1.9%)
Nasopharyngitis
0
3 (5.3%)
3 (0.3%)
Nervous System Disorders
2 (4.3%)
6 (10.5%)
9 (0.8%)
Headache
0
5 (8.8%)
8 (0.7%)
Table 11 – Summary of Adverse Events
in Clinical Trials
78,80
Table 12 – Summary of Adverse Events Occurring
in at Least 2 Patients by Preferred Term
78,80
AE=Adverse event.
a
Data for treatment with 20 IU/kg body weight from the first 4 hours after start of infusion.
AE=Adverse event.
a
Data for treatment with 20 IU/kg body weight from the first 4 hours after start of infusion.
b
One patient had 2 serious AEs that were unrelated to study medication. The patient was
retrospectively found not to have HAE.
c
Infusion related reaction 2 min after the start of infusion for the second attack of the patient
in this study; the event resolved after 4.6 hours and could not be clearly defined as allergic
or anaphylactoid.
