生控基因 (生寶)子宮頸癌TVGV-1疫苗 2015臨床試驗重新定位!!

生控子宮頸疫苗 大進展 2015-12-14 03:33 經濟日報 記者黃文奇／台北報導 生寶集團新藥子公司生控基因宣布，旗下自行開發的「子宮頸癌治療性疫苗TVGV-1」已展開美國第二期臨床試驗；而台灣第一期臨床試驗亦同步展開，與台大醫院合作，預計2016年完成試驗，證明TVGV-1在亞洲人種的安全性及耐受性。生控基因成立迄今邁入第三年，並且率先切入當前火紅治療性抗癌疫苗，且為免疫療法，利用可搭載特定疾病抗原的疫苗技術平台，切入不同癌症以及感染性疾病的利基市場，其發展中的主力產品TVGV-1即是針對子宮頸癌前病變的疫苗產品，同時還能兼顧預防的效果。在作用機轉上，生控表示，TVGV-1疫苗的作用機制屬於免疫療法的範疇，病患施打後，TVGV-1隨即啟動免疫系統專一性，能主動辨識出癌變細胞，進而如同導彈般精準地攻擊、摧毀，藉此清除癌變細胞，對病患產生完整的治療效果。目前生控基因委託全球子宮頸癌權威研究單位：美國約翰霍普金斯大學（Johns Hopkins University），針對TVGV-1進行的動物實驗，結果證實TVGV-1不但有效抑制腫瘤生長，相較於對照組，實驗組的存活比例更是呈現出100：0的壓倒性勝利，顯示TVGV-1能有效治療腫瘤。生控說，目前市面上現有的兩種HPV疫苗都屬於預防型疫苗，針對未感染HPV或未有性行為的女性施打疫苗才會有預防效果，但是已經有性行為或是已經感染HPV的廣大婦女則無法藉由該二疫苗來治療HPV感染，其施打的適當年齡分別為10-25歲、9-26歲，而子宮頸癌好發年齡為48歲。另外，子宮頸癌是目前僅次於乳癌的第二大婦癌疾病，根據WHO世界衛生組織最新的統計年報指出，全球每年有超過50萬名女性罹患子宮頸癌，超過26萬人死於子宮頸癌，癌前病變的族群更是十倍於子宮頸癌罹患人數，目前只能以傳統的手術、放療、化療醫治，大大影響患者的生活品質，國內生技新創公司TheVax生控基因的最新研發，為子宮頸癌癌前病變的治療帶來突破性發展。

Safety and Efficacy Study of TVGV-1 Vaccine to Treat HPV Induced Cervical HSIL/ This study is currently recruiting participants. Verified December 2015 by THEVAX Genetics Vaccine Sponsor: THEVAX Genetics Vaccine (生控基因) Collaborator: Clinical Research Management, Inc. Information provided by (Responsible Party): THEVAX Genetics Vaccine ClinicalTrials.gov Identifier: NCT02576561 First received: October 9, 2015/Last updated: December 1, 2015/Last verified: December 2015 Purpose The purpose of this research study is to test the safety and effectiveness of the investigational study vaccine, called TVGV-1. The study will test the vaccine in women with high grade HPV cervical infection. Study Type: Interventional/ Study Design: Allocation: Randomized/ Endpoint Classification: Safety/Efficacy Study/ Intervention Model: Parallel Assignment/ Masking: Double Blind (Subject, Caregiver, Investigator)/ Primary Purpose: Prevention

Official Title: Phase 2a Double-Blind, Randomized, Parallel Group, Dose-Ranging Study to Assess the Safety and Efficacy of Three Doses of TVGV-1 Vaccine Compared to Its Adjuvant, GPI-0100, in Subjects With Histologically Confirmed HPV Induced Cervical HSIL/ Primary Outcome Measures: Absence of histologic HSIL as assessed by conization, LEEP or hysterectomy (as determined by treating physician) at last study Visit 11, Day 270. [ Time Frame: DAY 270 ] [ Designated as safety issue: No ] The primary analysis for efficacy will be a comparison between subjects treated with and without the PEK fusion protein with respect to the percentage who present regression of HSIL at Day 270. Separate comparisons within each cohort will be performed using Fisher's exact test (or an appropriate analogue). No adjustment for multiple comparisons will be employed in these analyses. Additionally, a corresponding comparison across all study subjects combined will be performed, based on Cochran-Matel-Haenszel test stratified for cohort. Assessment of cutaneous toxicities (i.e., size, induration and time to resolution of skin reactions to vaccine). [Time Frame: DAY 270 ] [ Designated as safety issue: Yes ] Summaries of the data pertaining to the primary safety outcome of skin toxicity will be provided. Summaries will be provided for the within-cohort subsets of subjects treated with the active, and with the adjuvant alone; and the combined subsets across all three cohorts of subject treated with the active, with the adjuvant alone, and with the placebo. Serious adverse events will be described in narrative with the participant's demographics, treatment date, event, onset date, relationship to the study treatment and the descriptions of the actions and outcomes during this event. Any deaths occurring in the study will be summarized in narrative with the demographics, treatment duration, cause of death, date of death and additional information surrounding that serious adverse event. Secondary Outcome Measures: Absence of HPV16 in cervical cytological specimen. Absence of cervical dysplasia 6 months and 8 months after last dose of TVGV-1. [ Time Frame: DAY 270 ] [ Designated as safety issue: No ] The primary analysis for efficacy will be a comparison between subjects treated with and without the PEK fusion protein with respect to the percentage who present regression of HSIL at Day 270. Separate comparisons within each cohort will be performed using Fisher's exact test (or an appropriate analogue). No adjustment for multiple comparisons will be employed in these analyses. Additionally, a corresponding comparison across all study subjects combined will be performed, based on Cochran-Matel-Haenszel test stratified for cohort. Assessment of clinical or laboratory findings and other safety variables. [ Time Frame: DAy 270 ] [ Designated as safety issue: Yes ] Appropriate laboratory data will be transformed prior to analysis as defined in the Statistical Analysis Plan (SAP). Summaries will be presented for each evaluation time point, as well as for changes from baseline. Changes from baseline will also be presented using shift tables for selected laboratory parameters. Estimated Enrollment: 51 / Study Start Date: November 2015  Estimated Study Completion Date: June 2017/ Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)

Detailed Description: The purpose of the Phase 2a Study VAX 02-01 is to assess the safety and activity of TVGV-1 vaccine construct in achieving the absence of histologic HSIL (regression to LSIL or less) as assessed either by conization, LEEP or hysterectomy at last study Visit11, Day 270 (as determined by the treating physician). The objective of the TVGV-1 program is to develop a non-surgical alternative that is reliable, safe, and would avoid potential surgical risks such as preterm birth, perinatal mortality, risk of infertility, incontinence and disfigurement, as well as reduced cost and inconvenience for an otherwise economically productive young subject population.

Eligibility  Ages Eligible for Study: 21 Years to 50 Years/ Genders Eligible for Study: Female/ Accepts Healthy Volunteers: No/ Criteria/ Inclusion Criteria:/ / Female age 21 to 50 years/ Written informed consent in accordance with institutional guidelines/ Negative pregnancy test (urine and blood tests)/ Women of child bearing potential must agree to use contraception through one menstrual cycle post end of study or if early withdrawal, through what would have been visit 11. Methods include intrauterine device or double barrier method, hormonal contraceptive in combination with a double barrier method./ Positive cervical cytologic sample for HPV16 by an FDA approved test (cobas® HPV Test)/ Histologically confirmed, positive HSIL of CIN2+ or higher (only CIN2+/3 subjects will be selected) cervical biopsy, confirmed by external (independent) pathologist panel within the 12 weeks prior to enrollment. If the standard care biopsy is not available for evaluation by the independent pathologist, a fresh biopsy and endocervical curettage will be required. The extent of colposcopic HSIL disease should not involve more than two quadrants of the cervix. Biopsies should be taken from each affected quadrant/ Adequate visualization of entire cervix, cervical lesion(s) and squamous-columnar junction/ Normal electrocardiogram (ECG), laboratory values (chemistry, complete blood count) and urinalysis, as judged Grade 0-1 by per National Cancer Institute Common Toxicity Criteria (NCI-CTC)/ Agrees to Loop Electrosurgical Excision Procedure (LEEP), Cold Knife Conization (CKC) or Hysterectomy being performed at the end of study according to the standard-of-care/ Exclusion Criteria:/ / History of cancer (excluding basal cell carcinoma of the skin) including cervical cancer/ Eastern Cooperative Oncology Group (ECOG) performance status >2 (See Appendix G)/ Administration of any blood product within 3 months of enrollment/ Active infection requiring antimicrobial treatment that would interfere with interpretation of adverse events, cutaneous reactions or efficacy. Treatment of minor concurrent infections should be limited to less than 10 days./ Administration of any vaccine within 8 weeks of enrollment/ Participation in any study with an investigational compound or device within 30 days prior to signing informed consent/ Any hematologic disorder involving platelets or clotting abnormalities or any condition requiring treatment with transfusions, anticoagulants except platelet inhibitors (NSAIDs as needed for pain are permitted)/ Active drug or alcohol use or dependence that, in the opinion of the Site Investigator, would interfere with adherence to study protocol/ Skin conditions that require consistent use of topical corticosteroids or other local or systemic therapy that may interfere with interpretation or description of skin-related adverse events linked to vaccination/ The standard criteria for prospective clinical trials of medications developed by Drug-Induced Liver Injury Network (established by The National Institute of Diabetes and Digestive and Kidney Diseases) will be used to assess the laboratory test abnormalities. Normal range for these labs will typically be 5 - 40 IU/L for AST; 7 - 56 IU/L for ALT; 0.2 - 1.2 mg/dL for bilirubin. Subjects will be excluded if values are x 2-x 2.5 the upper limit/ Evidence of hematopoietic, cardiovascular, hepatic, renal, neurologic, psychiatric, dermatologic, immune disorder, or other disease that may interfere with assessment of safety or efficacy of vaccine activity as indicated in study objectives/ Any known allergic reaction to vaccine components/ Any other medical condition(s) that, in the judgment of the Site Investigator, might interfere with the study or require treatment that might interfere with the study/ Family member of the investigation study staff/ Pregnant or breast-feeding/ Inability to provide informed consent/ A subject with a history or expectation of noncompliance with medications or treatment protocol/ Receipt of (e.g. Gardasil® or Cervarix®) HPV preventative vaccines/ Excessive use of acetaminophen or other potentially hepatotoxic drugs/ Contacts and Locations/ Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies. / / Please refer to this study by its ClinicalTrials.gov identifier: NCT02576561/ / Contacts/ Contact: Furqan Haq, PhD 321-783-7189 furqan@vagenetics.com / Contact: Cheri Jones 321-783-7701 cheri@vaxgenetics.com /

Locations/ United States, Colorado/ Red Rocks OBGYN Not yet recruiting/ Lakewood, Colorado, United States, 80228/ Contact: Betsy Altschuler 303-985-9100/ Principal Investigator: Kelle Oberle, MD / United States, Florida/ Comprehensive Clinical Trials, LLC Recruiting/ West Palm Beach, Florida, United States, 33409/ Contact: Ronald Ackerman, MD 561-478-3177/ Contact: Linda Wyatt, RN 561-478-3177/ Principal Investigator: Ronald Ackerman, MD, FACOG / United States, Michigan/ Female Pelvic Medicine & Urogynecology Not yet recruiting/ Grand Rapids, Michigan, United States, 49503/ Contact: Beth Rogers, RN 616-588-1135/ Principal Investigator: Michael Bennett, MD / United States, North Carolina/ Unified Women's Clinical Research-Triad Recruiting/ Greensboro, North Carolina, United States, 27408/ Principal Investigator: James Tomblin / Unified Women's Clinical Research Recruiting/ Raleigh, North Carolina, United States, 27607/ Contact: Shari Vincent 919-788-4449/ Principal Investigator: Robert Littleton, MD / Unified Women's Clinical Research Recruiting/ Winston-Salem, North Carolina, United States, 27103/ Contact: Lisa Cumming 336-397-3703/ Principal Investigator: Lamar Parker, MD / United States, Utah/ Corner Canyon OBGYN/PRO Not yet recruiting/ Draper, Utah, United States, 84020/ Contact: Peggy Genebach, LPN, CCRC 385-695-2300/ Principal Investigator: Michael Twede, MD / United States, Virginia/ Insearch-Tidewater Clinical Research Recruiting/ Norfolk, Virginia, United States, 23502/ Contact: April Rusch 757-471-3375 ext 111/ Principal Investigator: Mehdi Parva, MD / Sponsors and Collaborators/ THEVAX Genetics Vaccine/ Clinical Research Management, Inc./ Investigators/ Study Director: Frank Douglas, PhD, MD THEVAX Genetics Vaccine / / Responsible Party: THEVAX Genetics Vaccine/ ClinicalTrials.gov Identifier: NCT02576561 History of Changes/ Other Study ID Numbers: VAX 02-01/ Study First Received: October 9, 2015/ Last Updated: December 1, 2015 / Health Authority: United States: Food and Drug Administration/  ClinicalTrials.gov processed this record on December 10, 2015

Phase I, Open-Label Study of the Safety, Tolerability, and Immunogenicity PEK Fusion Protein Vaccine The recruitment status of this study is unknown because the information has not been verified recently. Verified June 2013 by HealthBanks Biotech Co., Ltd..  Recruitment status was  Active, not recruiting/ Sponsor: HealthBanks Biotech Co., Ltd. (生寶臍帶血銀行)/ Information provided by (Responsible Party): HealthBanks Biotech Co., Ltd./ ClinicalTrials.gov Identifier: NCT01880411/ First received: June 13, 2013/ Last updated: June 14, 2013/ Last verified: June 2013

Purpose Phase I, Open-Label Study of the Safety, Tolerability, and Immunogenicity of a Three Dose Regimen of Escalating Doses of PEK Fusion Protein Vaccine in Women with LSIL or HSIL. PEK fusion protein vaccine (PEK + GPI-0100) is safe and well tolerated in patients with low-grade squamous intraepithelial lesions (LSIL) or high grade squamous intraepithelial lesions (HSIL) of the cervix and induces a measurable immune response. ClinicalTrials.gov processed this record on December 10, 2015

生控子宮頸癌癌症疫苗進二期Special Report | 特輯 2015. 7月號台灣館廠商媒合會逾300場　創新高企業兵分多路 商談絡繹不絕 – (環球生技)文 / 林亞歆、吳靜芳 美國CEO出馬與大廠談合作 除在農業生技大放異彩的瑞寶，生寶集團也拓展人用疫苗，在2012年成立子公司生控基因疫苗，聚焦於癌症、癌症前期及感染疾病的免疫療法。目前，生控利用集團二大專利疫苗技術平臺「逆向基因工程技術」和「對標靶細胞專一的融合抗原」，以綠膿桿菌外毒素融合蛋白疫苗平台技術為基礎，研發出的子宮頸癌癌症疫苗TVGV-1，已在2014年於美國完成第一期人體臨床試驗，並獲FDA許可進行臨床二期。目前子宮頸癌治療仍以化療、手術、單株抗體為主，市面上尚未有類似產品，若產品成功，將是臺灣公司開拓新穎蛋白質疫苗市場的新模式，可套用至其他癌症免疫療法研發。生控基因本次由美國執行長Frank L. Douglas領軍參展。Douglas曾任賽諾菲(Sanofi)集團安萬特藥廠(Aventis)的全球副總裁，在本次北美生技展親自出馬，與賽諾菲(Sanofi)及默克(Merck)碰面磋商合作可能。生控基因研發處處長吳嘉茂指出，公司此次BIO目標除了尋找適合的授權對象，也能藉此機會了解市場需求。有些對接的公司則希望可與生控合作多國多中心的臨床實驗，也有同是研究癌症免疫療法的香港大學教授討論合作。