Idioma:

Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial

Trimble, Cornelia L, Prof ; Morrow, Matthew P, PhD ; Kraynyak, Kimberly A, PhD ; Shen, Xuefei, PhD ; Dallas, Michael, PhD ; Yan, Jian, PhD ; Edwards, Lance, MD ; Parker, R Lamar, MD ; Denny, Lynette, MD ; Giffear, Mary, BS ; Brown, Ami Shah, PhD ; Marcozzi-Pierce, Kathleen, MA ; Shah, Divya, MS ; Slager, Anna M, MS ; Sylvester, Albert J, MS ; Khan, Amir, PhD ; Broderick, Kate E, PhD ; Juba, Robert J, MSCEP ; Herring, Timothy A, MPH ; Boyer, Jean, PhD ; Lee, Jessica, MPH ; Sardesai, Niranjan Y, PhD ; Weiner, David B, Prof ; Bagarazzi, Mark L, MD

The Lancet (British edition), 2015-11, Vol.386 (10008), p.2078-2088 [Periódico revisado por pares]

England: Elsevier Ltd

Texto completo disponível

Citações Citado por

Enviar para

Título:
Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial
Autor: Trimble, Cornelia L, Prof ; Morrow, Matthew P, PhD ; Kraynyak, Kimberly A, PhD ; Shen, Xuefei, PhD ; Dallas, Michael, PhD ; Yan, Jian, PhD ; Edwards, Lance, MD ; Parker, R Lamar, MD ; Denny, Lynette, MD ; Giffear, Mary, BS ; Brown, Ami Shah, PhD ; Marcozzi-Pierce, Kathleen, MA ; Shah, Divya, MS ; Slager, Anna M, MS ; Sylvester, Albert J, MS ; Khan, Amir, PhD ; Broderick, Kate E, PhD ; Juba, Robert J, MSCEP ; Herring, Timothy A, MPH ; Boyer, Jean, PhD ; Lee, Jessica, MPH ; Sardesai, Niranjan Y, PhD ; Weiner, David B, Prof ; Bagarazzi, Mark L, MD
Assuntos: Adult ; Cancer Vaccines - immunology ; Cancer Vaccines - therapeutic use ; Cervical cancer ; Cervical Intraepithelial Neoplasia - drug therapy ; Cervical Intraepithelial Neoplasia - virology ; Deoxyribonucleic acid ; DNA ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - immunology ; Double-Blind Method ; Female ; Genomes ; Human papillomavirus ; Human papillomavirus 16 ; Human papillomavirus 16 - genetics ; Human papillomavirus 16 - immunology ; Human papillomavirus 18 - genetics ; Human papillomavirus 18 - immunology ; Humans ; Immunization ; Immunotherapy ; Internal Medicine ; Oncogene Proteins, Viral - genetics ; Oncogene Proteins, Viral - immunology ; Papillomaviridae ; Papillomavirus E7 Proteins - genetics ; Papillomavirus E7 Proteins - immunology ; Papillomavirus Infections - drug therapy ; Papillomavirus Infections - virology ; Papillomavirus Vaccines - immunology ; Papillomavirus Vaccines - therapeutic use ; Repressor Proteins - genetics ; Repressor Proteins - immunology ; Treatment Outcome ; Uterine Cervical Neoplasms - drug therapy ; Uterine Cervical Neoplasms - virology ; Vaccines ; Vaccines, DNA - immunology ; Vaccines, DNA - therapeutic use ; Womens health ; Young Adult
É parte de: The Lancet (British edition), 2015-11, Vol.386 (10008), p.2078-2088
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Article-2
ObjectType-Feature-1
ObjectType-News-3
Descrição: Summary Background Despite preventive vaccines for oncogenic human papillomaviruses (HPVs), cervical intraepithelial neoplasia (CIN) is common, and current treatments are ablative and can lead to long-term reproductive morbidity. We assessed whether VGX-3100, synthetic plasmids targeting HPV-16 and HPV-18 E6 and E7 proteins, delivered by electroporation, would cause histopathological regression in women with CIN2/3. Methods Efficacy, safety, and immunogenicity of VGX-3100 were assessed in CIN2/3 associated with HPV-16 and HPV-18, in a randomised, double-blind, placebo-controlled phase 2b study. Patients from 36 academic and private gynaecology practices in seven countries were randomised (3:1) to receive 6 mg VGX-3100 or placebo (1 mL), given intramuscularly at 0, 4, and 12 weeks. Randomisation was stratified by age (<25 vs ≥25 years) and CIN2 versus CIN3 by computer-generated allocation sequence (block size 4). Funder and site personnel, participants, and pathologists were masked to treatment. The primary efficacy endpoint was regression to CIN1 or normal pathology 36 weeks after the first dose. Per-protocol and modified intention-to-treat analyses were based on patients receiving three doses without protocol violations, and on patients receiving at least one dose, respectively. The safety population included all patients who received at least one dose. The trial is registered at ClinicalTrials.gov (number NCT01304524 ) and EudraCT (number 2012-001334-33). Findings Between Oct 19, 2011, and July 30, 2013, 167 patients received either VGX-3100 (n=125) or placebo (n=42). In the per-protocol analysis 53 (49·5%) of 107 VGX-3100 recipients and 11 (30·6%) of 36 placebo recipients had histopathological regression (percentage point difference 19·0 [95% CI 1·4–36·6]; p=0·034). In the modified intention-to-treat analysis 55 (48·2%) of 114 VGX-3100 recipients and 12 (30·0%) of 40 placebo recipients had histopathological regression (percentage point difference 18·2 [95% CI 1·3–34·4]; p=0·034). Injection-site reactions occurred in most patients, but only erythema was significantly more common in the VGX-3100 group (98/125, 78·4%) than in the placebo group (24/42, 57·1%; percentage point difference 21·3 [95% CI 5·3–37·8]; p=0·007). Interpretation VGX-3100 is the first therapeutic vaccine to show efficacy against CIN2/3 associated with HPV-16 and HPV-18. VGX-3100 could present a non-surgical therapeutic option for CIN2/3, changing the treatment outlook for this common disease. Funding Inovio Pharmaceuticals.
Editor: England: Elsevier Ltd
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial

England: Elsevier Ltd

Buscando em bases de dados remotas. Favor aguardar.