Clinical trial NCT06577298: A Study to Evaluate the Safety and Immunogenicity of VLP-Polio in Infants and Toddlers
Official title: A Phase I/II Randomized, Double-blind, Positive-controlled Dose-exploration Study to Evaluate the Safety and Immunogenicity of a Virus-like Particle (VLP) Based Vaccine Against Poliomyelitis (VLP-Polio) in Infants From 6 Weeks of Age and Toddlers 12-18 Months of Age
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Poliomyelitis
Keywords: Vaccine
Trivalent
Immunogenicity
Safety
12-18 months toddlers
2 months infants
Lead sponsor: CanSino Biologics Inc.
Sponsor class: INDUSTRY
First posted: 2024-08-29
Enrollment: 480
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a phase I/II randomized, double-blind, and positive-controlled study. Participants in the phase I toddler group will receive 1 dose of either high dose VLP-Polio (Dose H) or control vaccine in a ratio of 3:1. The phase I infant cohort will have 4 arms randomly assigned to receive either investigational vaccine (Low-adjuvant dose VLP-Polio, Medium dose VLP-Polio, or High dose VLP-Polio or control vaccine in a ratio of 3:1. Phase II infant cohort will have 4 arms randomly assigned to receive either investigational vaccine (Low-adjuvant dose VLP-Polio, Medium dose VLP-Polio, or High dose VLP-Polio or control vaccine in a ratio of 3:1. Each infant participant will be administrated 3 doses of the assigned vaccine with 28 days apart, and the booster dose will be given when the infant is 12-18 months old. Enrollment of Phase I and Phase II will be staggered in descending order of age group but ascending order of dosing levels. Blood and mucosal samples will be collected for immunogenicity evaluation over the time course of the study.


Eligibility criteria: Inclusion Criteria:

* Healthy toddlers aged 12-18 months at the time of screening, and have completed primary immunization of polio vaccine according to the national government program in the first year of life.
* Healthy infants aged 6 weeks to 2 months (42 to 98 days, with the day of birth considered day of life 1), and who have not received any polio vaccines.
* Able to obtain written informed consent from parent(s) or legal guardian(s).
* Participants and their parents or legal guardian(s) can comply with trial procedures, are available for the duration of follow-up, and have a suitable telephone contact available.

Exclusion Criteria:

Exclusion criteria for the first dose:

* Current polio disease or history of polio disease.
* Toddlers who have an interval of less than 5 months since their last dose of the polio vaccine.
* Infants born at \< 37 weeks of gestation.
* Children with a birth weight \< 2500g and a body weight \< 3500g at the time of enrollment.
* Body temperature ≥37.5°C (the visit may be rescheduled when this criterion is met).
* Have congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.
* Any moderate or severe acute illness.
* Any abnormal vital signs.
* History of epilepsy, convulsions, or parent with congenital cognitive disability, dementia, or intellectual disabilities.
* Have received immunosuppressive treatment, cytotoxic treatment, glucocorticoid treatment, etc. (excluding local treatment, surface treatment of acute non-concurrent dermatitis, or spray treatment of allergic rhinitis).
* Received or plan to receive blood/plasma products or immunoglobulins throughout the study period or prior to study vaccination.
* History of serious adverse events and/or severe allergic reactions (e.g., systemic allergic reactions) to any component of the study vaccine.
* History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding (e.g., thalassemia, coagulation factor deficiencies, severe anemia at birth).
* Immunocompromised individuals with known or suspected immunodeficiency as determined by medical history and/or physical examination (e.g., history of pancreatic, liver, spleen, kidney disease or history of resection).
* Administration of other vaccines within 7 days.
* Participation in other interventional studies within 28 days prior to screening and/or during study participation.
* Household member or sibling who has received or is scheduled to receive OPV in the previous 3 months until 5 weeks after the third dose of the primary immunization series.
* The participant is a direct descendant (child or grandchild) of any person employed by the Sponsor, the contract research organization (CRO), the investigator, or study site personnel.
* History or current evidence of any condition or therapy which might confound the results of the study, interfere with the participant's participation for the full duration of the study, indicate suspected diseases, or is not in the best interest of the participants to participate, in the opinion of the treating investigator.
* Family history of any medical conditions, that in the investigating doctor's opinion, could affect the trial outcomes.
* Any reason or condition the investigator considers sufficient to make a participant ineligible for participation in the study.

Exclusion criteria for the subsequent doses:

* Severe allergic reaction after the previous vaccination.
* Serious adverse events caused by the previous vaccination.
* Newly identified symptoms or newly occurred cases after the first vaccination that do not meet the inclusion criteria for the first dose, or that meet the exclusion criteria for the first dose. The decision to discontinue participation is determined by the investigator.
* Other reasons for exclusion considered by the investigating doctor .

Primary outcomes:
measure: Phase I: Percentage of participants with solicited adverse events (AEs)
timeFrame: Within 7 days after each vaccination
measure: Phase II: Percentage of participants with solicited adverse events (AEs)
timeFrame: Within 7 days after each vaccination
measure: Phase II: Seroconversion rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3
timeFrame: Day 0 before vaccination and on Day 28 after the 3rd dose vaccination
Secondary outcomes:
measure: Phase I: Percentage of participants with unsolicited AEs
timeFrame: Within 28 days after each vaccination
measure: Phase I: Percentage of participants with solicited AEs
timeFrame: Within 30 minutes after each vaccination
measure: Phase I: Percentage of participants experiencing serious adverse events (SAEs)
timeFrame: Through study completion, Toddlers about 6 months, Infant about 20-22 months.
measure: Phase I: Geometric mean titer (GMT) of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in toddlers
timeFrame: Day 0 before vaccination and on Day 28 after the vaccination
measure: Phase I: Seroprotection rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in toddlers
timeFrame: Day 0 before vaccination and on Day 28 after the vaccination
measure: Phase I: Seroconversion rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in toddlers
timeFrame: Day 0 before vaccination and on Day 28 after the vaccination
measure: Phase I: GMT of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in infants
timeFrame: Day 0 before vaccination and on Day 28 after the 3rd dose vaccination
measure: Phase I: Seroprotection rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in infants
timeFrame: Day 0 before vaccination and on Day 28 after the 3rd dose vaccination
measure: Phase I: Seroconversion rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in infants
timeFrame: Day 0 before vaccination and on Day 28 after the 3rd dose vaccination
measure: Phase II: Percentage of participants with unsolicited AEs
timeFrame: Within 28 days after each vaccination
measure: Phase II: Percentage of participants with solicited AEs
timeFrame: Within 30 minutes after each vaccination
measure: Phase II: Percentage of participants experiencing SAEs
timeFrame: Through study completion, Toddlers about 6 months, Infant about 20-22 months.
measure: Phase II: GMT of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3
timeFrame: Day 0 before vaccination and on Day 28 after the 3rd dose vaccination
measure: Phase II: Seroprotection rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3
timeFrame: Day 0 before vaccination and on Day 28 after the 3rd dose vaccination
measure: Phase II: GMT of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in extended immunogenicity subgroup participants.
timeFrame: Month 6 after the 3rd dose vaccination
measure: Phase II: Seroprotection rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in extended immunogenicity subgroup participants.
timeFrame: Month 6 after the 3rd dose vaccination
measure: Phase II: Seroconversion rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in extended immunogenicity subgroup participants.
timeFrame: Month 6 after the 3rd dose vaccination
Other outcomes:
measure: Phase II: GMT of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in extended immunogenicity subgroup participants.
timeFrame: Day 0 before booster vaccination, on Day 28 and Month 6 after the booster vaccination
measure: Phase II: Seroprotection rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in extended immunogenicity subgroup participants.
timeFrame: Day 0 before booster vaccination, on Day 28 and Month 6 after the booster vaccination
measure: Phase II: Seroconversion rate of neutralizing antibodies against Sabin and wild-type poliovirus type 1, 2, and 3 in extended immunogenicity subgroup participants.
timeFrame: Day 0 before booster vaccination, on Day 28 and Month 6 after the booster vaccination
measure: Phase II: GMT of poliovirus type-specific neutralizing and binding antibodies (IgA, IgG, IgM) in stool samples in extended immunogenicity subgroup participants
timeFrame: Day 0 before vaccination, on Day 14 and Day 28 after the 3rd dose vaccination, on Day 0 before the booster vaccination, on Day 14 and Day 28 after the booster vaccination
measure: Phase II: GMI (geometric mean fold increase) of poliovirus type-specific neutralizing and binding antibodies (IgA, IgG, IgM) in stool samples in extended immunogenicity subgroup participants
timeFrame: Day 0 before vaccination, on Day 14 and Day 28 after the 3rd dose vaccination, on Day 0 before the booster vaccination, on Day 14 and Day 28 after the booster vaccination
measure: Phase II: GMT of poliovirus type-specific neutralizing and binding antibodies (IgA, IgG, IgM) in nasal samples in extended immunogenicity subgroup participants
timeFrame: Day 0 before vaccination, on Day 14 and Day 28 after the 3rd dose vaccination, on Day 0 before the booster vaccination, on Day 14 and Day 28 after the booster vaccination
measure: Phase II: GMI of poliovirus type-specific neutralizing and binding antibodies (IgA, IgG, IgM) in nasal samples in extended immunogenicity subgroup participants
timeFrame: Day 0 before vaccination, on Day 14 and Day 28 after the 3rd dose vaccination, on Day 0 before the booster vaccination, on Day 14 and Day 28 after the booster vaccination
Locations:
city: Jakarta
country: Indonesia
facility: Dr. Cipto Mangunkusumo Hospital
Study officials:
affiliation: Dr. Cipto Mangunkusumo Hospital
name: Nina Putri, Dr
role: PRINCIPAL_INVESTIGATOR
References: