ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial.

Francisco A Garcia, Karl Ulrich Petry, Laila Muderspach, Michael A. Gold, Patricia Braly, Christopher P. Crum, Marianne Magill, Michael Silverman, Robert G. Urban, Mary Lynne Hedley, Kathleen J. Beach

Research output: Contribution to journalArticle

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Abstract

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. LEVEL OF EVIDENCE: I

Original languageEnglish (US)
Pages (from-to)317-326
Number of pages10
JournalObstetrics and Gynecology
Volume103
Issue number2
StatePublished - Feb 2004

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Cervical Intraepithelial Neoplasia
Randomized Controlled Trials
Placebos
Therapeutics
Conization
Safety
Human papillomavirus 18
Injections
Human papillomavirus 16
ZYC101a
Plasmids
Pathology
Biopsy
DNA
Population

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Garcia, F. A., Petry, K. U., Muderspach, L., Gold, M. A., Braly, P., Crum, C. P., ... Beach, K. J. (2004). ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstetrics and Gynecology, 103(2), 317-326.

ZYC101a for treatment of high-grade cervical intraepithelial neoplasia : a randomized controlled trial. / Garcia, Francisco A; Petry, Karl Ulrich; Muderspach, Laila; Gold, Michael A.; Braly, Patricia; Crum, Christopher P.; Magill, Marianne; Silverman, Michael; Urban, Robert G.; Hedley, Mary Lynne; Beach, Kathleen J.

In: Obstetrics and Gynecology, Vol. 103, No. 2, 02.2004, p. 317-326.

Research output: Contribution to journalArticle

Garcia, FA, Petry, KU, Muderspach, L, Gold, MA, Braly, P, Crum, CP, Magill, M, Silverman, M, Urban, RG, Hedley, ML & Beach, KJ 2004, 'ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial.', Obstetrics and Gynecology, vol. 103, no. 2, pp. 317-326.
Garcia, Francisco A ; Petry, Karl Ulrich ; Muderspach, Laila ; Gold, Michael A. ; Braly, Patricia ; Crum, Christopher P. ; Magill, Marianne ; Silverman, Michael ; Urban, Robert G. ; Hedley, Mary Lynne ; Beach, Kathleen J. / ZYC101a for treatment of high-grade cervical intraepithelial neoplasia : a randomized controlled trial. In: Obstetrics and Gynecology. 2004 ; Vol. 103, No. 2. pp. 317-326.
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abstract = "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. LEVEL OF EVIDENCE: I",
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T1 - ZYC101a for treatment of high-grade cervical intraepithelial neoplasia

T2 - a randomized controlled trial.

AU - Garcia, Francisco A

AU - Petry, Karl Ulrich

AU - Muderspach, Laila

AU - Gold, Michael A.

AU - Braly, Patricia

AU - Crum, Christopher P.

AU - Magill, Marianne

AU - Silverman, Michael

AU - Urban, Robert G.

AU - Hedley, Mary Lynne

AU - Beach, Kathleen J.

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N2 - 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. LEVEL OF EVIDENCE: I

AB - 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. LEVEL OF EVIDENCE: I

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