Safety and Immunogenicity Study of Recombinant Trivalent Rotavirus Subunit Vaccine in Healthy Infants and Toddlers

Rotavirus Gastroenteritis Clinical Trial

Official title:

A Phase II Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant Trivalent Subunit Rotavirus Vaccine in Healthy Infants Aged 6-12 Weeks and Healthy Toddlers Aged 7-71 Months

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05621655
• Other study ID #: MKKCT2021002
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 8, 2023
• Est. completion date: April 2024

Study information

• Verified date: May 2023
• Source: MAXVAX Biotechnology Limited Liability Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the immunogenicity, safety and immune persistence of recombinant trivalent rotavirus subunit vaccine in healthy infants aged 6-12 weeks and healthy toddlers aged 7-71 months.

Description:

This clinical trial is aimed to evaluate the immunogenicity, safety and immune persistence of recombinant trivalent rotavirus subunit vaccine in Chinese healthy infants aged 6-12 weeks and healthy toddlers aged 7-71 months.The subjects will be divided into 12 subgroups. Two different immune regimens and two dose levels will be evaluated in each age group. Toddlers aged 7-71 months will receive two intramuscular injections on Day 0 and 28 or three intramuscular injections on Day 0, 28 and 56. Infants aged 6-12 weeks will receive three intramuscular injections on Day 0, 28 and 56 or Day 0, 56 and 112. Two dose (mid dose and high dose) will be included in each age group. To maintain blindness in the trial, in each age group with fixed immune regimen, subjects will be randomized in a 1:1:1 ratio to receive mid dose vaccine, high dose vaccine, or placebo.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1512
• Est. completion date: April 2024
• Est. primary completion date: April 29, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 71 Months

Eligibility

Inclusion Criteria:

1. Healthy infants aged 6-12 weeks and healthy toddlers aged 7-71 months;

2. Legally acceptable representative (guardian) properly informed about the study and having signed the informed consent form (ICF). Exclusion Criteria:

First dose exclusion criteria:

1. Axillary temperature >37.0? before vaccination;

2. Recepit of any rotavirus vaccine in the past;

3. History of intussusception or suffering from intussusception or history of any chronic gastrointestinal disease, including congenital malformations of the gastrointestinal tract that are likely to cause intussusception (such as Meckel's diverticulum);

4. Congenital malformations, developmental disorders, genetic defect, severe malnutrition, etc.;

5. Subjects aged 2 years or younger with history of dystocia, suffocation rescue, or nervous system damage;

6. Subjects aged 2 years or younger with history of premature birth (<37 weeks' gestation) or low birth weight (weight at birth of<2500 g);

7. History of convulsions, epilepsy and cerebral palsy, or mental illness and family history;

8. History of severe anaphylactic reaction to vaccination, or allergy to any components of the study vaccine;

9. Acute diseases (such as fever>39.0?) or acute exacerbation of chronic disease within 3 days before vaccination;

10. Receipt of immune enhancement (including oral or intravenous immunoglobulin, but hepatitis B immunoglobulin is acceptable) or immunosuppressive therapy (continuous oral or intravenous infusion for more than 14 days) within 3 months;

11. Recepit of live attenuated vaccines within 14 days, or other vaccines within 7 days;

12. Congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), or other autoimmune diseases;

13. History of coagulation abnormalities (such as lack of blood coagulation factors, blood coagulopathy);

14. Primary and secondary impairment of immune function (history of thyroid, pancreas, liver, spleen resection, or treatment due to thyroid disease within the past 12 months);

15. Concurrent participation or plan to participate in another clinical trial throughout the study;

16. According to the judgment of the investigator, the subject has any other factors that are not suitable for participating in the clinical trial.

Subsequent vaccination exclusion criteria:

17. Severe allergic reaction after the previous injection of study vaccine;

18. Serious adverse reactions that are causally related to the previous vaccination;

19. After the first vaccination, subjects with newly discovered or newly happened diseases that meet the first dose exclusion criteria will be determined by the investigator whether to continue participating the study;

20. Other reasons for exclusion judged by the investigator.

Related Conditions & MeSH terms

• Gastroenteritis
• Rotavirus Gastroenteritis
• Rotavirus Infections

Intervention

Biological:
• Mid dose Recombinant Trivalent Subunit Rotavirus Vaccine
0.5 mL of vaccine containing a total of 60 µg of protein (20 µg of each P type) adjuvanted with 0.5 mg aluminum hydroxide.
• High dose Recombinant Trivalent Subunit Rotavirus Vaccine
0.5 mL of vaccine containing a total of 90 µg of protein (30 µg of each P type) adjuvanted with 0.5 mg aluminum hydroxide.
• Placebo
0.5 mL per dose, containing 0.5 mg aluminium hydroxide adjuvant.

Locations

Country	Name	City	State
China	Ningling County Center for Disease Control and Prevention	Shangqiu	Henan
China	Shangqiu Liangyuan District Center for Disease Control and Prevention	Shangqiu	Henan

Sponsors (2)

Lead Sponsor	Collaborator
MAXVAX Biotechnology Limited Liability Company	Henan Center for Disease Control and Prevention

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of adverse events	Incidence of adverse events within 30 minutes after each dose. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.	Within 30 minutes after each vaccination
Primary	The incidence of adverse events	Incidence of adverse events within 14 days after each dose. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.	Within 14 days after each vaccination
Primary	The incidence of adverse events	Incidence of adverse events Day 15 to 28/30 after each dose. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.	Day 15 to 28/30 after each vaccination
Primary	The incidence of adverse events	Incidence of adverse events within 28/30 days after each dose. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.	Within 28/30 days after each vaccination
Primary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus Immunoglobulin A (IgA)	Measured by ELISA at baseline and 30 days after the last vaccination.	Day 30 after the last vaccination
Primary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus Immunoglobulin G (IgG)	Measured by ELISA at baseline and 30 days after the last vaccination.	Day 30 after the last vaccination
Primary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus neutralizing antibody	Neutralizing antibodies will be measured by Micro serum neutralization test at baseline and 30 days after the last vaccination.	Day 30 after the last vaccination
Primary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus IgA	Seroconversion is defined as a = 4-fold rise in IgA titer compared with Baseline.	Day 30 after the last vaccination
Primary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus IgG	Seroconversion is defined as a = 4-fold rise in IgG titer compared with Baseline.	Day 30 after the last vaccination
Primary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus neutralizing antibody	Seroconversion is defined as a = 2.7-fold rise in neutralizing antibody titer compared with Baseline.	Day 30 after the last vaccination
Secondary	Incidence of serious adverse events (SAE)	Incidence of serious adverse events throughout the study.	From the first vaccination to 12 months after the last vaccination.
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus IgA	Measured by ELISA.	Day 90 after the last vaccination
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus IgA	Measured by ELISA.	Day 180 after the last vaccination
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus IgA	Measured by ELISA.	Day 360 after the last vaccination
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus IgG	Measured by ELISA.	Day 90 after the last vaccination
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus IgG	Measured by ELISA.	Day 180 after the last vaccination
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus IgG	Measured by ELISA.	Day 360 after the last vaccination
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus neutralizing antibody	Neutralizing antibodies will be measured by Micro serum neutralization test.	Day 90 after the last vaccination
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus neutralizing antibody	Neutralizing antibodies will be measured by Micro serum neutralization test.	Day 180 after the last vaccination
Secondary	Geometric Mean Titers (GMT) of anti-P[4], anti-P[6], anti-P[8] rotavirus neutralizing antibody	Neutralizing antibodies will be measured by Micro serum neutralization test.	Day 360 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus IgA	Seroconversion is defined as a = 4-fold rise in IgA titer compared with Baseline.	Day 90 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus IgA	Seroconversion is defined as a = 4-fold rise in IgA titer compared with Baseline.	Day 180 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus IgA	Seroconversion is defined as a = 4-fold rise in IgA titer compared with Baseline.	Day 360 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus IgG	Seroconversion is defined as a = 4-fold rise in IgG titer compared with Baseline.	Day 90 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus IgG	Seroconversion is defined as a = 4-fold rise in IgG titer compared with Baseline.	Day 180 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus IgG	Seroconversion is defined as a = 4-fold rise in IgG titer compared with Baseline.	Day 360 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus neutralizing antibody	Seroconversion is defined as a = 2.7-fold rise in neutralizing antibody titer compared with Baseline.	Day 90 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus neutralizing antibody	Seroconversion is defined as a = 2.7-fold rise in neutralizing antibody titer compared with Baseline.	Day 180 after the last vaccination
Secondary	Seroconversion rates of anti-P[4], anti-P[6], anti-P[8] rotavirus neutralizing antibody	Seroconversion is defined as a = 2.7-fold rise in neutralizing antibody titer compared with Baseline.	Day 360 after the last vaccination