Rotavirus Vaccine for Healthy Adults

Overseen By Christina Rostad, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Centers for Disease Control and Prevention

Must not be taking: Corticosteroids, Immunomodulators, Cytotoxic drugs, others

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 240

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and immune response of a new inactivated rotavirus vaccine in healthy adults. Participants will receive three doses of the vaccine through an injection, with two different dose levels being tested. The study seeks healthy individuals aged 18 to 45 who agree to follow study procedures and have no significant medical conditions or recent illnesses. Those in good health and interested in contributing to vaccine research may find this opportunity suitable. As a Phase 1 trial, participants will be among the first to receive this new vaccine, assisting researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, if you are on medications that affect the immune system, you may need to stop them, as chronic use of such medications is an exclusion criterion.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the CDC-9 Inactivated Rotavirus Vaccine (IRV) has been tested in animals and found to be safe and effective. These studies demonstrated that the vaccine triggered a strong immune response, suggesting it might work well in humans too. However, since this is an early study in humans, the main focus is on safety.

Some rotavirus vaccines have been linked to a small risk of a bowel blockage called intussusception. This has not been observed with the CDC-9 IRV so far. Since this trial is in the early phase, it primarily checks the vaccine's safety for people. This step is crucial to confirm safety before more extensive testing can occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for rotavirus, which typically involves oral vaccines like Rotarix or RotaTeq, the CDC-9 Inactivated Rotavirus Vaccine (IRV) is unique because it is administered via intramuscular injection. Researchers are excited about this treatment because it features an inactivated form of the virus, potentially offering a safer option for those who might be at risk from live attenuated vaccines. With two different dosages being tested, 7.5 µg and 3.75 µg, scientists are eager to find the optimal balance between efficacy and safety, potentially broadening protection against rotavirus infections.

What evidence suggests that the CDC-9 Inactivated Rotavirus Vaccine might be an effective treatment for rotavirus?

Research has shown that the CDC-9 Inactivated Rotavirus Vaccine (IRV) could effectively prevent rotavirus infections. Similar vaccines have been very successful, preventing the disease in 80-90% of cases. In animal studies, the CDC-9 IRV was safe and produced a strong immune response. One study found that when administered by injection, this vaccine also protected the gut by boosting intestinal immunity. In this trial, participants will receive either a 7.5 µg or a 3.75 µg dose of the CDC-9 IRV via intramuscular injection. These findings suggest that the vaccine could help build protection against rotavirus. ^{1 4 5 6 7}

Who Is on the Research Team?

Christina Rostad, MD

Principal Investigator

Emory Children's Center - Vaccine Research Clinic (ECC-VRC)

Lauren Nolan, PA-C

Principal Investigator

Emory Children's Center - Vaccine Research Clinic (ECC-VRC)

Are You a Good Fit for This Trial?

Healthy adults aged 18 to 45 can participate in this trial. They will be testing a new vaccine for rotavirus. To join, participants must not have any health conditions that could affect the study or their safety.

Inclusion Criteria

I am a man who can father a child and will use condoms.

Provides written informed consent prior to any study procedures being performed

Agrees to collection of venous blood per protocol

Exclusion Criteria

Breastfeeding or plans to breastfeed during the study period

Acute illness within 72 hours prior to enrollment

Positive pregnancy test at screening or prior to each vaccine administration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive three doses of the inactivated rotavirus vaccine (IRV) or placebo administered intramuscularly at Days 1, 29, and 57

8 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety, reactogenicity, and immunogenicity, including solicited and unsolicited adverse events, and immunogenicity labs

6 months

Multiple visits (in-person and virtual) up to Day 237

What Are the Treatments Tested in This Trial?

Interventions

• CDC-9 Inactivated Rotavirus Vaccine (IRV)

Trial Overview The trial is studying an inactivated rotavirus vaccine given by muscle injection at two different dose levels (7.5 µg and 3.75 µg) compared with a placebo, administered in three doses over time.

How Is the Trial Designed?

Group I: 7.5 µg CDC-9 Inactivated Rotavirus Vaccine (IRV) Intramuscular (IM) Experimental Treatment 2 Interventions

20 healthy adults will be administered via IM injection a single dose of IRV at days 1, 29 and 57

Group II: 3.75 µg CDC-9 Inactivated Rotavirus Vaccine (IRV) Intramuscular (IM) Experimental Treatment 2 Interventions

20 healthy adults will be administered via IM injection a single dose of IRV at days 1, 29 and 57

Who Is Running the Clinical Trial?

Centers for Disease Control and Prevention

Lead Sponsor

Trials

902

Recruited

25,020,000+

Emory-Children's Center

Collaborator

Trials

5

Recruited

5,001,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Bill and Melinda Gates Foundation

Collaborator

Trials

428

Recruited

23,060,000+

Published Research Related to This Trial

The oral, live rotavirus vaccine (RRV-TV) is safe and effective for infants, significantly reducing the incidence of severe gastroenteritis caused by rotavirus, which is a leading cause of hospitalizations and healthcare costs in children.

The recommended vaccination schedule includes three doses administered at 2, 4, and 6 months of age, which is expected to prevent most physician visits and at least two-thirds of hospitalizations and deaths related to rotavirus in the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rotavirus vaccine for the prevention of rotavirus gastroenteritis among children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). [2017]

The CDC-9 strain inactivated rotavirus vaccine (IRV) has been developed to improve efficacy in infants from low-income countries and enhance safety compared to live oral rotavirus vaccines, which can cause severe side effects like intussusception.

In studies with guinea pigs, the IRV demonstrated strong immune responses, including high levels of IgG and neutralizing activity against various rotavirus strains, indicating its potential as an effective alternative for global immunization efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inactivated human rotavirus vaccine induces heterotypic antibody response: correction and development of IgG avidity assay. Velasquez, DE., Wang, Y., Jiang, B.[2018]

Inactivated influenza vaccines (IIVs) are generally safe and well tolerated in pregnant women and children under 5 years old, with low rates of adverse events, although ongoing safety monitoring is essential.

IIVs elicit strong antibody responses, with efficacy rates ranging from 50%-70% in pregnant women and 20%-90% in young children against lab-confirmed influenza, indicating that the benefits of vaccination outweigh potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Immunogenicity, Efficacy and Effectiveness of Inactivated Influenza Vaccines in Healthy Pregnant Women and Children Under 5 Years: An Evidence-Based Clinical Review. Bansal, A., Trieu, MC., Mohn, KGI., et al.[2023]

The candidate inactivated rotavirus vaccine (IRV) demonstrated strong immunogenicity in gnotobiotic piglets, inducing high levels of rotavirus-specific IgG and neutralizing antibodies after three doses.

The IRV provided effective protection against rotavirus infection, as evidenced by reduced shedding of the virus after an oral challenge, supporting its potential as a viable alternative vaccine for infants in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inactivated rotavirus vaccine induces protective immunity in gnotobiotic piglets. Wang, Y., Azevedo, M., Saif, LJ., et al.[2010]

A total of 98 confirmed cases of intussusception were reported among infants vaccinated with the rotavirus vaccine, with 60 cases occurring within one week of vaccination, indicating a potential safety concern.

The incidence of intussusception was found to be at least four times higher than expected based on statistical estimates, leading to the voluntary withdrawal of the rotavirus vaccine from the market and the cessation of its routine use in US infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intussusception among recipients of rotavirus vaccine: reports to the vaccine adverse event reporting system. Zanardi, LR., Haber, P., Mootrey, GT., et al.[2019]

A review of 3175 reports from the Vaccine Adverse Event Reporting System (VAERS) found that the MMR vaccine in adults had a low incidence of serious adverse events (5%), with no new safety concerns identified during the study period from 2003 to 2013.

Among reports of pregnant women receiving the MMR vaccine, the majority did not experience adverse events, highlighting the need for better education on vaccine recommendations, as MMR is contraindicated during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Following Measles, Mumps, and Rubella Vaccine in Adults Reported to the Vaccine Adverse Event Reporting System (VAERS), 2003-2013. Sukumaran, L., McNeil, MM., Moro, PL., et al.[2019]

The introduction of rotavirus vaccines, Rotarix and RotaTeq, has been shown to be safe and effective in large clinical trials with over 60,000 infants, significantly reducing the disease burden of rotavirus infection.

Despite their safety, there is a very rare risk of intussusception, which necessitates ongoing postmarketing surveillance to monitor for any unexpected adverse events as the vaccines are administered to a larger population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of postlicensure safety of rotavirus vaccines, with emphasis on intussusception. Bines, JE., Patel, M., Parashar, U.[2009]

A review of 41,792 adverse event reports related to inactivated poliovirus vaccine (IPV) from 2000 to 2012 found that 95% of reports were for children under 7 years, with the majority being non-serious events, indicating a favorable safety profile for IPV.

The analysis showed no new or unexpected safety issues associated with IPV, and reports of sudden infant death syndrome were consistent with patterns seen in other vaccines, suggesting that IPV does not pose additional risks compared to other immunizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000-12. Iqbal, S., Shi, J., Seib, K., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06485258

NCT06485258 | CDC-9 Inactivated Rotavirus Vaccine (IRV ... Vaccination with IRV has shown to be safe and immunogenic in animal studies. A rotavirus vaccine with greater efficacy and stronger immunogenic response could ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12150633/

A report for the fifth International Workshop on Rotavirus and ... Rotavirus vaccine effectiveness is inversely related to the level of child mortality in the country with higher effectiveness observed in ...

3. stacks.cdc.gov stacks.cdc.gov/view/cdc/147684/cdc_147684_DS1.pdf

Rotavirus vaccines: progress and new developments Expert opinion: Considerable evidence over the past decade has demonstrated high effectiveness (80–90%) of rotavirus vaccines at preventing ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X10008042

Inactivated rotavirus vaccine induces protective immunity in ... We demonstrated that thermally inactivated CDC-9 formulated with aluminum phosphate was highly immunogenic and at least partially protected gnotobiotic piglets ...

5. nature.com nature.com/articles/s41598-017-18973-9

Inactivated rotavirus vaccine by parenteral administration ... Our study is the first to show that parenterally administered IRV can induce mucosal immunity in the gut, in addition to strong serum antibody response.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4514286/

Inactivated human rotavirus vaccine induces heterotypic ... This IRV of 3 doses elicits high titers of IgG, neutralizing activity to homotypic and heterotypic human strains and IgG avidity in guinea pigs.

7. cdc.gov cdc.gov/vaccine-safety/vaccines/rotavirus.html

Rotavirus Vaccine Safety Some studies suggest that rotavirus vaccination possibly causes a small increase in the risk of intussusception, a type of bowel blockage.