日本大学医学部産婦人科学系 産婦人科学分野
MILACLE study
【Scientific Title】
A Phase I/II study of mucosal immunotherapy using HPV-targeting Lactobacillus-based vaccine, IGMKK16E7, for treatment of HPV16-related high-grade squamous intraepithelial lesions: MILACLE study
【Region】
Japan
【Condition】
High-grade squamous intraepithelial lesions (HSIL/CIN2-3)
【Narrative Objectives】
To evaluate the safety of oral administration with IGMKK16E7 to patients with HSIL/CIN2-3 and decide the recommended human dose to obtain the optimal efficacy.
【Basic objectives -Others】
To examine the relationship between HPV E7 expression levels and the efficacy of IGMKK16E7.
【Primary outcomes】
A safety of IGMKK16E7 and pathological regression of HSIL/CIN2-3.
【Key secondary outcomes】
TH1 immune responses to E7, cytological regression of /CIN2-3, and Clearance of HPV genome.
【Study design】
Basic design/Parallel
Randomization/Randomized
Blinding/Double blind -all involved are blinded
Control/Placebo
【Intervention】
No. of arms/4
Purpose of intervention/Treatment
Type of intervention/MedicineVaccine
Interventions/Control_1/
Low-dose of IGMKK16E7 (an attenuated HPV16E7-expressing Lactobacillus casei) is administered daily. All patients received four rounds of oral vaccination at weeks 1, 2, 4,
and 8. Each dose of IGMKK16E7 or placebo is administered orally once each morning after
fasting for five days each treatment week.
Interventions/Control_2/
Middle-dose of IGMKK16E7 (an attenuated HPV16E7-expressing Lactobacillus casei) is administered daily. All patients received four rounds of oral vaccination at weeks 1, 2, 4,
and 8. Each dose of IGMKK16E7 or placebo is administered orally once each morning after fasting for five days each treatment week.
Interventions/Control_3/
High-dose of IGMKK16E7 (an attenuated HPV16E7-expressing Lactobacillus casei) is administered daily. All patients received four rounds of oral vaccination at weeks 1, 2, 4, and 8. Each dose of IGMKK16E7 or placebo is administered orally once each morning after
fasting for five days each treatment week.
Interventions/Control_4/
Placebo is administered daily. All patients received four rounds of oral vaccination at weeks 1, 2, 4, and 8. Each dose of IGMKK16E7 or placebo is administered orally once each morning after fasting for five days each treatment week.
【Eligibility】
Age, Gender/20years-old<= ,45years-old>,Female
Key inclusion criteria/
20-45 years-old health female who are diagnosed as HSIL/CIN2 and HSIL/CIN3 by histological examination and infected with HPV 16 alone or HPV16+other types.
Key exclusion criteria/
(1) Immune compromised host or person who receive immunosuppressive therapy,
(2) Patients who is suspected as invasive cancer,
(3) Patients who has a previous history of hypersensitivity to Lactobacillus-content food/drug or milk.
(4) Pregnant women or patients who expected to get pregnant,
(5) Breast feeder mother.
Target sample size/164
【Research contact person】
Kei Kawana
Nihon University School of Medicine, Department of Obstetrics and Gynecology
30-1, Oyaguchi kami-cho,Itabachi-ku, Tokyo 173-8610, Japan
【Funding Source】
Japan Agency for Medical Research and Development (AMED)
【Other related organizations】
GLOVACC Inc.
【Institutions】
Nihon University Itabashi Hospital, Keio University Hospital, University of Tsukuba Hospital, Kyushu University Hospital
【Progress】
Date of protocol fixation/April 20,2018
Anticipated trial start date/May 19,2019
Last follow-up date/June 30,2022
【URL related to results】
Protocol_FINAL_MILACLEstudy
SAP_FINAL_MILACLEstudy
MILACLEstudy