ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial.
OBJECTIVE
The objective of this study was to assess the safety and efficacy of a novel therapeutic, ZYC101a, for the treatment of women with histologically confirmed cervical intraepithelial neoplasia (CIN) 2/3. ZYC101a contains plasmid-DNA-encoding fragments derived from the E6 and E7 proteins of human papillomavirus (HPV) 16 and 18, and is formulated within small biodegradable microparticles.


METHODS
A multicenter, double-blind, randomized, placebo-controlled trial was conducted in a group of women with biopsy-confirmed CIN 2/3. Subjects were randomized to 3 intramuscular doses of either placebo or ZYC101a (100 or 200 microg). Six months after the first injection, subjects underwent cervical conization. The primary endpoint for this study was histologically confirmed resolution of CIN 2/3. A total of 161 subjects were randomized, dosed, and evaluated for safety. After central pathology review, 127 subjects were evaluable for efficacy.


RESULTS
The most common adverse events were related to the injection site, were mild to moderate, and did not worsen at later treatments. The proportion of subjects who resolved was higher in the ZYC101a groups compared to placebo (43% versus 27%), but the difference was not statistically significant (P =.12). In a prospectively defined population of women younger than 25 years (n = 43), resolution was significantly higher in the combined ZYC101a groups compared to placebo (70% versus 23%; P =.007). ZYC101a activity was not restricted to HPV-16-or HPV-18-positive lesions.


CONCLUSIONS
ZYC101a was shown to be well tolerated in all patients and to promote the resolution of CIN 2/3 in women younger than 25 years.


METHODS
I
Garcia
Francisco
F
Department of Obstetrics and Gynecology, University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ 85724, USA. fcisco@email.arizona.edu
Petry
Karl Ulrich
KU
Muderspach
Laila
L
Gold
Michael A
MA
Braly
Patricia
P
Crum
Christopher P
CP
Magill
Marianne
M
Silverman
Michael
M
Urban
Robert G
RG
Hedley
Mary Lynne
ML
Beach
Kathleen J
KJ
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004247:DNA / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014764:Viral Proteins / Q000008:administration & dosage; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000473:pathology*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins; C482279:ZYC101a; D004247:DNA