Based on encouraging results from a phase 1 trial, Genticel initiated a randomized, double-blind, placebo-controlled study designed to demonstrate the efficacy of GTL001 (recombinant E7 HPV 16/18) adjuvanted with imiquimod in inducing viral clearance at one year post vaccination. Sustained clearance will be assessed two years after vaccination. The study enrolled women HPV 16 and/or 18 positive, with normal or ASCUS/LSIL cytology results. All women underwent a colposcopy at baseline with biopsy of any visible lesion to exclude patients with CIN2+ histology.
A total of 2371 women unaware of their HPV status were pre-screened with HPV genotyping test and cytology, of which 85 qualified for inclusion and additional screening procedures (3.6%). In addition, 504 women previously known to be positive for high-risk HPV infection were directly screened. Out of these 589 screened subjects, 350 were screen failures, 239 (40%) were randomly assigned to treatment, and 236 received at least one dose of study drug.
The most frequent reasons for screen failure were not having HPV 16/18 infection (60%), not having cervical cytology evaluation with a normal, ASCUS, or LSIL (15%), withdrawal consent (7.5%), and concomitant episode of high-grade lesion (7%).
The population enrolled was generally healthy, with mean age of 35.6 years. Seventy-eight (78) % of women were HPV 16 positive while 19% were HPV 18 positive and 3% were positive for both HPV 16 and 18. A majority of subjects had abnormal cytology at baseline (172 ASCUS/LSIL, 73% versus 64 NILM, 27%). Seventy seven (77) subjects had biopsy at screening due to visible lesion(s) at colposcopy, of which 22 had CIN1 results. There were no significant differences between groups for demographic or baseline characteristics.
Three subjects did not receive the second injection of GTL001 because of severe local reactions following the first injection but remained in the study. Two subjects withdrew from the study during the vaccination period, one for non-compliance with study procedures and one for adverse event of pharyngitis/tonsillitis. Three subjects withdrew from the study during the follow-up period (2 subjects were lost to follow-up and one withdrew consent for reason independent of the study). A total of 231 subjects (97%) reached the 12-month visit and were evaluable for viral clearance at one year.
Results of the 12-month analysis will be presented.