A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis.
BACKGROUND
Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.


METHODS
A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.


RESULTS
Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated.


CONCLUSIONS
Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.
Pachl
Jan
J
Charles University, Prague, Czech Republic.
Svoboda
Petr
P
Jacobs
Frédérique
F
Vandewoude
Koenraad
K
van der Hoven
Ben
B
Spronk
Peter
P
Masterson
Gary
G
Malbrain
Manu
M
Aoun
Mickael
M
Garbino
Jorge
J
Takala
Jukka
J
Drgona
Lubos
L
Burnie
James
J
Matthews
Ruth
R
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000935:Antifungal Agents / Q000627:therapeutic use*; D002175:Candida / Q000145:classification / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010919:Placebos; D011994:Recombinant Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000935:Antifungal Agents; D018841:HSP90 Heat-Shock Proteins; D010919:Placebos; D011994:Recombinant Proteins; D000666:Amphotericin B; C512268:efungumab