Diane M Harper1, Pekka Nieminen2, Gilbert Donders3, Mark H Einstein4, Francisco Garcia5, Warner K Huh6, Mark H Stoler7, Katerina Glavini8, Gemma Attley9, Jean-Marc Limacher10, Berangere Bastien11, Elizabeth Calleja12. 1. Department of Family and Community Medicine, Obstetrics and Gynecology, University of Missouri Kansas City, 7900 Lee's Summit Road, Kansas City, MO 64139, USA. Electronic address: harperdi@med.umich.edu. 2. Department of Obstetrics and Gynaecology, Helsinki University Hospital and Helsinki University, Box 615, 00029 HUS, Helsinki, Finland. Electronic address: pekka.nieminen@hus.fi. 3. Department of Obstetrics and Gynaecology, University Hospital Antwerp, Wilrijksesteenweg 10, 2000 Antwerp-Ekeren, Belgium. Electronic address: Gilbert.Donders@uza.be. 4. Department of Obstetrics and Gynecology, Albert Einstein Cancer Center and Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA. Electronic address: me399@njms.rutgers.edu. 5. Center of Excellence in Women's Health at the University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85714, USA. Electronic address: Francisco.Garcia@pima.gov. 6. Department of Obstetrics and Gynecology, University of Alabama, 1700 6th Avenue South, WIC Room 10250, Birmingham, AL 35233, USA. Electronic address: whuh@uabmc.edu. 7. Surgical Pathology, P.O. Box 800214, Department of Pathology, University of Virginia Health System, University of Virginia, Charlottesville, VA, USA. Electronic address: mhs2e@me.comall. 8. Roche Pharmaceutical Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Building 93, Room 7.38.01, Grenzacherstrasse 124, Basel 4070, Switzerland. Electronic address: katerina.glavini@roche.com. 9. Roche Pharmaceutical Research & Early Development, Roche Innovation Center New York, 430 E. 29th Street New York City, New York 10016, USA. Electronic address: gemma.attley.ga1@roche.com. 10. Department of Medical Affairs, Transgene SA, 400 Bb Gonthier d'Andernach Parc d'innovation, CS80166, 67405 Illkirch-Graffenstaden Cedex, France. Electronic address: jean-marc.limacher@ch-colmar.fr. 11. Department of Biostatistics, Transgene S.A., Boulevard Gonthier d'Andernach Parc d'innovation, CS80166, 67405 Illkirch-Graffenstaden Cedex, France. Electronic address: bastien@transgene.fr. 12. Roche Pharmaceutical Research & Early Development, Roche Innovation Center New York, 430 E. 29th Street New York City, New York 10016, USA. Electronic address: elizabethcalleja@netscape.net.
Abstract
BACKGROUND: While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types. METHODS:Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug. RESULTS: Of the 129 women randomized tovaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24% vs. 10%, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21% vs. 0%, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions. CONCLUSIONS: The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.
RCT Entities:
BACKGROUND: While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types. METHODS:Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug. RESULTS: Of the 129 women randomized to vaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24% vs. 10%, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21% vs. 0%, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions. CONCLUSIONS: The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.
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