Norovirus Gastroenteritis, Norovirus Infections
Conditions
Keywords
INT101, Norovirus Vaccine, Norovirus Gastroenteritis, Healthy Adults, Phase 1, Immunogenicity, GII.3, GII.4, GII.17, Intramuscular Injection, Trivalent, Dose-Escalation, Placebo-Controlled, Single-Blind
Brief summary
This study is being conducted to evaluate the safety and immunogenicity of INT101, an investigational vaccine intended to prevent norovirus gastroenteritis, in healthy adults. INT101 contains multivalent norovirus antigens (GII.3, GII.4, and GII.17) and is administered as an intramuscular injection. Participants will receive either INT101 or a placebo, given three times at 4-week intervals. This is a single-center, single-blind, randomized, dose-escalation, placebo-controlled, multiple-dose, Phase 1 clinical trial. Approximately 30 healthy adult participants will be enrolled and randomly assigned to receive either a low dose or high dose of INT101, or a matching placebo, in a 2:1 ratio within each dose group. The primary objective is to evaluate the safety of multiple intramuscular doses of INT101 compared to placebo. The secondary objective is to evaluate the immunogenicity (antibody response) of INT101 compared to placebo. Participants will be followed for approximately 6 months after their last dose to monitor safety and immune response.
Detailed description
This is a single-center, single-blind, randomized, dose-escalation, placebo-controlled, multiple-dose, Phase 1 clinical trial designed to evaluate the safety and immunogenicity of INT101 intramuscular injection in healthy adults. INT101 is a vaccine candidate containing multivalent norovirus antigens (genotypes GII.3, GII.4, and GII.17), formulated at 20 μg per antigen (60 μg total) per 0.5 mL vial. The matching placebo is identical in formulation and appearance, excluding the active norovirus antigens. Approximately 30 participants will be enrolled into two dose groups: a low-dose group (30 μg/0.25 mL) and a high-dose group (60 μg/0.5 mL). Each dose group consists of a sentinel cohort followed by a main cohort. Within each cohort, participants are randomized in a 2:1 ratio to receive either INT101 or placebo. Enrollment proceeds in a staggered, dose-escalation manner: Sentinel A (low dose) is dosed first, followed by a Day 7 DSMB safety review before proceeding to Cohort A. DSMB (Data and Safety Monitoring Board) evaluations are conducted at Day 7 after the first and third (last) doses within Cohort A before advancing to the high-dose groups (Sentinel B and Cohort B). Each participant receives 3 intramuscular injections (into the deltoid muscle) at 4-week intervals (Visit 2/Baseline, Visit 4, Visit 6). The study includes a screening period (up to 4 weeks), a treatment period (8 weeks, 3 doses), and a follow-up period of approximately 6 months after the last dose, for a total of 9 study visits. Safety endpoints include immediate adverse events, solicited local and systemic adverse events, unsolicited adverse events, serious adverse events, and clinically significant changes in laboratory tests, physical examinations, and vital signs. Immunogenicity endpoints include seroconversion rate, geometric mean titer (GMT), and geometric mean ratio (GMR) of norovirus antibodies, assessed at Days 7, 28, 35, 56, 63, 84, and 224 relative to baseline.
Interventions
BIOLOGICALINT101 Low Dose
Norovirus multivalent antigen vaccine (GII.3, GII.4, GII.17), total 30 μg per 0.25 mL, administered via intramuscular injection into the deltoid muscle, 3 doses at 4-week intervals.
BIOLOGICALINT101 High Dose
Norovirus multivalent antigen vaccine (GII.3, GII.4, GII.17), total 60 μg per 0.5 mL, administered via intramuscular injection into the deltoid muscle, 3 doses at 4-week intervals.
BIOLOGICALINT101 Placebo (0.25 mL)
Matching placebo identical in formulation and appearance to INT101, excluding the active norovirus antigens; 0.25 mL, administered via intramuscular injection into the deltoid muscle, 3 doses at 4-week intervals.
BIOLOGICALINT101 Placebo (0.5 mL)
Matching placebo identical in formulation and appearance to INT101, excluding the active norovirus antigens; 0.5 mL, administered via intramuscular injection into the deltoid muscle, 3 doses at 4-week intervals.
Sponsors
InThera Inc. Korea
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Intervention model description
This study employs a sentinel-cohort, dose-escalation design. Sentinel A (low dose) is enrolled and dosed first; after a Day 7 DSMB safety review, Cohort A (low dose) proceeds. DSMB (Data and Safety Monitoring Board) evaluations at Day 7 after the first and third (last) doses in Cohort A determine whether dose escalation to the high-dose groups (Sentinel B, then Cohort B) may proceed. Within each sentinel/cohort, participants are randomized 2:1 to receive INT101 or matching placebo.
Eligibility
Sex/Gender
ALL
Age
19 Years to 48 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults aged 19 to 48 years (inclusive) as of the screening visit * Body Mass Index (BMI) of 18.0 to 30.0 kg/m\^2 (inclusive) at screening * Women and men of reproductive potential willing to use a highly effective contraceptive method (hormonal contraceptives, intrauterine device/system, or sterilization) from 30 days prior to the first investigational product administration through 2 months after the last administration * For female participants, a negative pregnancy test result at screening * Agreement not to donate blood or receive blood transfusion during the study period * Judged to be healthy by the investigator based on clinical judgment, medical history, and physical examination at screening * Able to understand the purpose of the study and voluntarily provide written informed consent to participate and comply with study restrictions
Exclusion criteria
* Autoimmune disease (e.g., rheumatoid arthritis, hypothyroidism) at screening * Uncontrolled hypertension (BP not controlled below 140/90 mmHg, or 130/80 mmHg if diabetic, despite maximal doses of 3 or more antihypertensive agents) or diabetes (HbA1c \>7.0%) * Neurological disease (e.g., epilepsy, seizure, Guillain-Barre syndrome) * Asthma * Uncontrolled bleeding disorder or receipt of anticoagulant therapy * History of immunodeficiency or immune dysfunction * History of malignancy within 5 years prior to the first dose (excised skin lesions or basal cell carcinoma successfully treated with no recurrence for 3 or more years may be enrolled at investigator discretion) * Suspected or history of substance abuse prior to study participation * Significant alcohol consumption (21 or more drinks/week for men, 14 or more drinks/week for women) or excessive smoking (20 or more cigarettes/day) within 1 month prior to the first dose * History of gastrointestinal illness (e.g., enteritis, diarrhea, abdominal pain, vomiting) within 14 days prior to the first dose * Positive result for HIV antigen/antibody, Hepatitis B surface Antigen (HBsAg), Anti-Hepatitis C Virus (Anti-HCV), or syphilis at screening * Participation in another clinical trial involving an investigational drug or device within 6 months prior to the first dose * Receipt of immunoglobulin or blood products within 6 months prior to the first dose, or planned receipt during the study * Receipt of immunosuppressive or immunomodulatory agents (e.g., Azathioprine, Cyclosporine) within 6 months prior to the first dose * Receipt of cytotoxic chemotherapy that may affect immune function * History of radiation therapy * Receipt or planned receipt of any vaccine other than the investigational product within 4 weeks before or after each investigational product administration * High fever (38C or above) within 3 days prior to the first dose, or clinically significant suspected acute infection * Use of analgesics or antipyretics within 1 day prior to investigational product administration * Chronic steroid use (Prednisolone more than 10 mg/day for more than 14 consecutive days), unless discontinued for 6 months or more prior to screening (topical, nasal, inhaled, or ophthalmic steroids permitted regardless of dose) * Inflammation at or near the planned injection site * Planned blood donation during the study period * Pregnant or breastfeeding women * History of serious adverse event, allergy, or hypersensitivity reaction related to vaccination * History of organ or hematopoietic stem cell transplant prior to study participation * Clinically significant abnormal laboratory test result at screening * Suspected or history of alcohol abuse * Known hypersensitivity to the investigational product or its components * Chronic underlying disease, congenital disease, or mental illness judged by the investigator to interfere with study conduct or completion * Any other condition judged by the investigator to make the participant unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Immediate Adverse Events (AEs) | Within 30 minutes after each investigational product administration (up to 3 doses) | Number and proportion of participants experiencing immediate adverse events occurring within 30 minutes after each administration of the investigational product. |
| Incidence of Solicited Local Adverse Events | Within 7 days after each investigational product administration | Number and proportion of participants experiencing solicited local adverse events (e.g., injection site pain, erythema, swelling) following each investigational product administration. |
| Incidence of Solicited Systemic Adverse Events | Within 7 days after each investigational product administration | Number and proportion of participants experiencing solicited systemic adverse events (e.g., fever, fatigue, headache, myalgia) following each investigational product administration. |
| Incidence of Unsolicited Adverse Events | Within 28 days after each investigational product administration, or occurring between Visit 8 and Visit 9 | Number and proportion of participants experiencing unsolicited adverse events not specifically listed on the diary card, following each investigational product administration. |
| Incidence of Serious Adverse Events (SAEs) | From first investigational product administration up to Day 224 (approximately 32 weeks) | Number and proportion of participants experiencing serious adverse events, regardless of causal relationship to the investigational product, from the first dose through the end of follow-up. |
| Incidence of Clinically Significant Abnormalities in Laboratory Tests, Physical Examinations, and Vital Signs | From baseline (Day 0, first investigational product administration) through Day 224 (end of study, approximately 32 weeks) | Number and proportion of participants with a shift from normal or not clinically significant abnormal at baseline to clinically significant abnormal at any post-baseline visit in laboratory test results, physical examination findings, or vital sign measurements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion Rate of Norovirus Antibodies | Day 7, 28, 35, 56, 63, 84, and 224 after the first investigational product administration, compared to baseline | Proportion of participants achieving seroconversion, defined as a ≥4-fold increase from baseline in norovirus IgG, IgA, or HBGA blocking antibody titer, at each post-baseline time point. |
| Geometric Mean Titer (GMT) of Norovirus Antibodies | Day 7, 28, 35, 56, 63, 84, and 224 after the first investigational product administration, compared to baseline | Geometric mean titer of norovirus antibodies (IgG, IgA, and HBGA blocking antibody) at each post-baseline time point compared to baseline. |
| Geometric Mean Ratio (GMR) of Norovirus Antibodies | Day 7, 28, 35, 56, 63, 84, and 224 after the first investigational product administration, compared to baseline | Geometric mean ratio (fold-rise from baseline) of norovirus antibody titers at each post-baseline time point compared to baseline. |
Countries
South Korea
Contacts
CONTACTJeongwon Project Manager
PRINCIPAL_INVESTIGATORJoonsup Yeom, MD, PhD
Severance Hospital, Yonsei University College of Medicine
Outcome results
None listed