Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.
BACKGROUND
Hereditary angioedema due to C1 inhibitor deficiency is characterized by recurrent acute attacks of swelling that can be painful and sometimes life-threatening.


METHODS
We conducted two randomized trials to evaluate nanofiltered C1 inhibitor concentrate in the management of hereditary angioedema. The first study compared nanofiltered C1 inhibitor concentrate with placebo for treatment of an acute attack of angioedema. A total of 68 subjects (35 in the C1 inhibitor group and 33 in the placebo group) were given one or two intravenous injections of the study drug (1000 units each). The primary end point was the time to the onset of unequivocal relief. The second study was a crossover trial involving 22 subjects with hereditary angioedema that compared prophylactic twice-weekly injections of nanofiltered C1 inhibitor concentrate (1000 units) with placebo during two 12-week periods. The primary end point was the number of attacks of angioedema per period, with each subject acting as his or her own control.


RESULTS
In the first study, the median time to the onset of unequivocal relief from an attack was 2 hours in the subjects treated with C1 inhibitor concentrate but longer than 4 hours in those given placebo (P=0.02). In the second study, the number of attacks per 12-week period was 6.26 with C1 inhibitor concentrate given as prophylaxis, as compared with 12.73 with placebo (P<0.001); the subjects who received the C1 inhibitor concentrate also had significant reductions in both the severity and the duration of attacks, in the need for open-label rescue therapy, and in the total number of days with swelling.


CONCLUSIONS
In subjects with hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.)
Zuraw
Bruce L
BL
University of California, San Diego, USA. bzuraw@ucsd.edu
Busse
Paula J
PJ
White
Martha
M
Jacobs
Joshua
J
Lumry
William
W
Baker
James
J
Craig
Timothy
T
Grant
J Andrew
JA
Hurewitz
David
D
Bielory
Leonard
L
Cartwright
William E
WE
Koleilat
Majed
M
Ryan
Walter
W
Schaefer
Oren
O
Manning
Michael
M
Patel
Pragnesh
P
Bernstein
Jonathan A
JA
Friedman
Roger A
RA
Wilkinson
Robert
R
Tanner
David
D
Kohler
Gary
G
Gunther
Glenne
G
Levy
Robyn
R
McClellan
James
J
Redhead
Joseph
J
Guss
David
D
Heyman
Eugene
E
Blumenstein
Brent A
BA
Kalfus
Ira
I
Frank
Michael M
MM
D000208:Acute Disease; D000328:Adult; D000704:Analysis of Variance; D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000517:prevention & control*; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000009:adverse effects / Q000627:therapeutic use*; D051056:Complement Inactivating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D036103:Nanotechnology; D016016:Proportional Hazards Models; D014462:Ultrafiltration
D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents