Clinical Trials List
Protocol NumberEV-BR1701
NCT Number(ClinicalTrials.gov Identfier)N/A
Completed
2018-06-01 - 2024-12-31
Phase III
Terminated7
ICD-10B34.1
Enterovirus infection, unspecified
ICD-9047.0
Meningitis due to coxsackie virus
A Phase III, Multiple-center, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of an Adjuvanted Inactivated Enterovirus 71 (EV71) Vaccine in Healthy Infants and Children
-
Trial Applicant
ENIMMUNE CORPORATION
-
Sponsor
Enimmune Corporation
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Hsiao-chuan Lin Division of Pediatrics
- Hung-Chih Lin Division of Pediatrics
- Shu-Fen Wu Division of Pediatrics
- Ming-Lun Yeh Division of Pediatrics
- An-Chyi Chen Division of Pediatrics
- Hsiang-Yu Lin Division of Pediatrics
- Chang-Ching Wei Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 張家瑗 Division of Pediatrics
- 洪妙秋 Division of Pediatrics
- Keh-Gong Wu Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 許雅淇 Division of Pediatrics
- 丁佩如 Division of Pediatrics
- FANG-LIANG HUANG Division of Pediatrics
- 吳孟哲 Division of Pediatrics
- Ming-Chih LIN Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 戴君芙 Division of Pediatrics
- Luan-Yin Chang Division of Pediatrics
- 賴貞吟 Division of Pediatrics
- Chun-yi Lu Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 郭貞孍 Division of Pediatrics
- 江明洲 Division of Pediatrics
- 吳怡萱 Division of Pediatrics
- 朱世明 Division of Pediatrics
- 賴美吟 Division of Pediatrics
- 許凱翔 Division of Pediatrics
- 謝育嘉 Division of Pediatrics
- 林瑞瑩 Division of Pediatrics
- 楊長佑 Division of Pediatrics
- Chi-Long Chen Division of Pediatrics
- Cheng-Hsun Chiu Division of Pediatrics
- 傅仁煇 Division of Pediatrics
- Jen Fu Hsu Division of Pediatrics
- 李建忠 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 高峻凱 Division of Pediatrics
- 李政翰 Division of Pediatrics
- Cheng-Han Lee Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Completed
Condition/Disease
Enterovirus 71 (EV71)
Objectives
1. Pimary objective:(1) Efficacy:- To evaluate the efficacy of EV71 vaccine in healthy infants and young children(aged 2 months to 6 years old) against EV71-associated HFMD/Herpangina. Thevaccine efficacy will be determined within one year period after completion oftwo-regimen injection of EV71 vaccine.(2) Immunogenicity:- To evaluate the immunogenicity by the response rate (i.e. seroprotection rate, SPR)which is the proportion of the vaccinated subjects with serum neutralizing antibody(NT Ab) titers ≥ 1:32 28 days after 2nd vaccination (Day 56).2. Secondary objectives:(1) Efficacy:- To evaluate the efficacy of vaccination against the severe complications, includingneurologic, pulmonary edema, and cardiorespiratory failure, of EV71 associatedHFMD/HA diseases within one-year period after completion of full vaccination.- To evaluate the efficacy of vaccination against the hospitalization of EV71associated HFMD/HA diseases within one-year period after completion of fullvaccination.(2) Immunogenicity, immune persistence and lot consistency:- To evaluate the immunogenicity of EV71 vaccine with two-dose regimen inhealthy infants and young children (aged 2 months to 6 years old).- To evaluate the immune persistence of EV71 vaccine with two-dose regimen inhealthy infants and young children (aged 2 months to 6 years old).- To evaluate lot-to-lot consistency by comparing the immunogenicity induced by 3independent EV71 vaccine clinical materials in healthy infants and young children(aged 2 months to 6 years old)(3) Safety:- To evaluate the safety of EV71 vaccine in healthy infants and young children(aged 2 months to 6 years old)
Test Drug
nactivated EV71 whole viral particles adjuvanted with aluminum (Al(OH)3)
Active Ingredient
nactivated EV71 whole viral particles adjuvanted with aluminum (Al(OH)3)
Dosage Form
Injection
Dosage
1 μg viral protein with adjuvant 150 μg Al (OH)3
Endpoints
1. Primary endpoint:
(1) Efficacy:
Confirmed EV71-associated HFMD/HA diseases* rate (attack rate) of the vaccine
group and placebo group
* EV71-associated HFMD/Herpangina diseases will be confirmed by positive EV71 viral
isolation
(2) Immunogenicity :
The SPR (seroprotection rate, the proportion of the subjects with NT Ab against EV71
titer≥1:32) 28 days after 2nd vaccination (Day 56) ≥ 90%.
2. Secondary endpoints:
(1) Efficacy:
- The confirmed severe HFMD/HA and HFMD/HA hospitalization cases of the
vaccine and placebo groups
Severe HFMD/HA complications include neurologic, pulmonary edema, and
cardiorespiratory failure, of EV71 associated HFMD/HA diseases.
(2) Immunogenicity, Immune persistence, and lot consistency:
- The seroconversion rate (SCR)*, SPR, geometric mean titer (GMT), and
geometric mean titer increase ratio (GMTR) of EV71 neutralizing antibody (NT
Ab) on Day 56 , Day 196 and Day 392.
*SCR is defined as the percentage of subjects achieving either a pre-vaccination
neutralizing antibody titer <1:8 and a post-vaccination neutralizing antibody titer ≥1:32,
OR a pre-vaccination neutralizing antibody titer ≥1:8 and a minimum 4-fold increase in
post-vaccination neutralizing antibody titer.
- The SPR on Day 196 ≥ 70%.
- Immune persistence is assessed by the above-mentioned parameters throughout to
Day 392.
- Lot consistency is assessed by the comparisons of the GMT of EV71 neutralizing
antibody titer on Day 56 induced by 3 independent EV71 vaccine clinical
materials. The 95% confidence intervals between groups will be within the margin
of 0.5 to 2.
(3) Safety:
- Occurrence and severity of solicited injection site relations and general reactions
within 7 days following each injection
- Occurrence and severity of unsolicited adverse events within 28 days following
each injection.
- Occurrence and relations with vaccination of some special AE during the 6-months
follow-up period (up to Day 196).
- Occurrence and relations with vaccination of serious adverse events (SAEs) during
the one-year follow-up period (up to Day 392).
(1) Efficacy:
Confirmed EV71-associated HFMD/HA diseases* rate (attack rate) of the vaccine
group and placebo group
* EV71-associated HFMD/Herpangina diseases will be confirmed by positive EV71 viral
isolation
(2) Immunogenicity :
The SPR (seroprotection rate, the proportion of the subjects with NT Ab against EV71
titer≥1:32) 28 days after 2nd vaccination (Day 56) ≥ 90%.
2. Secondary endpoints:
(1) Efficacy:
- The confirmed severe HFMD/HA and HFMD/HA hospitalization cases of the
vaccine and placebo groups
Severe HFMD/HA complications include neurologic, pulmonary edema, and
cardiorespiratory failure, of EV71 associated HFMD/HA diseases.
(2) Immunogenicity, Immune persistence, and lot consistency:
- The seroconversion rate (SCR)*, SPR, geometric mean titer (GMT), and
geometric mean titer increase ratio (GMTR) of EV71 neutralizing antibody (NT
Ab) on Day 56 , Day 196 and Day 392.
*SCR is defined as the percentage of subjects achieving either a pre-vaccination
neutralizing antibody titer <1:8 and a post-vaccination neutralizing antibody titer ≥1:32,
OR a pre-vaccination neutralizing antibody titer ≥1:8 and a minimum 4-fold increase in
post-vaccination neutralizing antibody titer.
- The SPR on Day 196 ≥ 70%.
- Immune persistence is assessed by the above-mentioned parameters throughout to
Day 392.
- Lot consistency is assessed by the comparisons of the GMT of EV71 neutralizing
antibody titer on Day 56 induced by 3 independent EV71 vaccine clinical
materials. The 95% confidence intervals between groups will be within the margin
of 0.5 to 2.
(3) Safety:
- Occurrence and severity of solicited injection site relations and general reactions
within 7 days following each injection
- Occurrence and severity of unsolicited adverse events within 28 days following
each injection.
- Occurrence and relations with vaccination of some special AE during the 6-months
follow-up period (up to Day 196).
- Occurrence and relations with vaccination of serious adverse events (SAEs) during
the one-year follow-up period (up to Day 392).
Inclution Criteria
Main inclusion criteria:
(1) Healthy children aged from 2 months to 6 years old (i.e. 2 months old and < 7 years
old) at the time of first vaccination.
(2) Subject’s guardians are able and willing to comply with study procedures and provide
the signed informed consent.
(3) Subject is able and can comply with the requirements of the protocol.
(4) Subject with body temperature 38°C.
(1) Healthy children aged from 2 months to 6 years old (i.e. 2 months old and < 7 years
old) at the time of first vaccination.
(2) Subject’s guardians are able and willing to comply with study procedures and provide
the signed informed consent.
(3) Subject is able and can comply with the requirements of the protocol.
(4) Subject with body temperature 38°C.
Exclusion Criteria
Main exclusion criteria:
(1) Subject with previous known exposure to Enterovirus 71 (EV71) or receiving EV71
investigational vaccines.
(2) Subject with a history of herpangina, hand-foot-mouth disease, and acute hemorrhagic
conjunctivitis associated with enterovirus infection in the past 3 months.
(3) Subject with a history of hypersensitivity to vaccines, or a history of allergic disease or
reactions likely to be exacerbated by any component of the vaccine.
(4) Subject with gestation < 35 weeks.
(5) Subject with birth weight < 2.5 kg.
(6) Family history of congenital or hereditary immunodeficiency.
(7) Epilepsy, seizures or convulsions history, or family history of mental illness
(8) Severe malnutrition or dysgenopathy.
(9) Major congenital defects or serious chronic illness, including perinatal brain damage.
(10) Subject diagnosed of having autoimmune disease (e.g., celiac disease, type I diabetes,
lupus (SLE), juvenile dermatomyositis, scleroderma, juvenile idiopathic arthritis (JIA),
immune (or idiopathic) thrombocytopenia purpura).
(11) Bleeding disorder diagnosed by a doctor or significant bruising or hemostatic difficulties with IM injections or blood draws.
(12) Any acute febrile illness 3 days prior to administrating the first vaccination.
(13) Use of any investigational product (including drug, vaccine) within 30 days prior to
vaccination or planned use during the study period.
(14) Administration of any vaccines within 14 days prior to randomization.
(15) Use of immunoglobulins or any blood products within 3 months prior to vaccination.
(16) Chronic administration (defined as 14 days) of immunosuppressants or other
immunomodulators or systemic corticosteroids within 6 months prior to vaccination.
(17) Any condition that in the opinion of the investigator may interfere with the evaluation
of study objectives.
(1) Subject with previous known exposure to Enterovirus 71 (EV71) or receiving EV71
investigational vaccines.
(2) Subject with a history of herpangina, hand-foot-mouth disease, and acute hemorrhagic
conjunctivitis associated with enterovirus infection in the past 3 months.
(3) Subject with a history of hypersensitivity to vaccines, or a history of allergic disease or
reactions likely to be exacerbated by any component of the vaccine.
(4) Subject with gestation < 35 weeks.
(5) Subject with birth weight < 2.5 kg.
(6) Family history of congenital or hereditary immunodeficiency.
(7) Epilepsy, seizures or convulsions history, or family history of mental illness
(8) Severe malnutrition or dysgenopathy.
(9) Major congenital defects or serious chronic illness, including perinatal brain damage.
(10) Subject diagnosed of having autoimmune disease (e.g., celiac disease, type I diabetes,
lupus (SLE), juvenile dermatomyositis, scleroderma, juvenile idiopathic arthritis (JIA),
immune (or idiopathic) thrombocytopenia purpura).
(11) Bleeding disorder diagnosed by a doctor or significant bruising or hemostatic difficulties with IM injections or blood draws.
(12) Any acute febrile illness 3 days prior to administrating the first vaccination.
(13) Use of any investigational product (including drug, vaccine) within 30 days prior to
vaccination or planned use during the study period.
(14) Administration of any vaccines within 14 days prior to randomization.
(15) Use of immunoglobulins or any blood products within 3 months prior to vaccination.
(16) Chronic administration (defined as 14 days) of immunosuppressants or other
immunomodulators or systemic corticosteroids within 6 months prior to vaccination.
(17) Any condition that in the opinion of the investigator may interfere with the evaluation
of study objectives.
The Estimated Number of Participants
-
Taiwan
1256 participants
-
Global
3982 participants
