Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules

NCT01266850 | Completed Phase 4 Results

• 2 other identifiers: 08-0017N01AI80006C
• Study Type: interventional
• Target: 1,384
• Locations: 1 country
• Sites: 13

Brief Summary

Rotavirus, sometimes called the "stomach flu," is the most common cause of severe diarrhea in children. Vaccines can prevent many types of infections and work by causing the body to make proteins called antibodies that fight infection. For some vaccines, more than one vaccination is needed so that the body will make enough antibodies to fight infection. The vaccines (RotaTeq® or Rotarix® oral vaccines) given in this study are recommended for infants by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP). These vaccines require either 2 or 3 vaccinations to be effective. Healthy infants between 6 weeks and 14 weeks, 6 days of age at Visit 1 will participate for about 10-12 months. Study procedures include reaction assessment and blood sample.

Conditions

Rotavirus Infection

Keywords

vaccine, rotavirus, gastroenteritis, infants

Outcome Measures

Primary Outcomes (3)

• Number of Participants Developing a Serum Anti-rotavirus Immunoglobulin (Ig) A Titer of 20 or Greater in the WC3 IgA Assay

  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA assay to determine the anti-rotavirus IgA antibody titer. A participant met the threshold of a positive response if the post vaccination anti-rotavirus IgA antibody titer was 20 or greater.

  3-6 weeks after the last vaccination

• Number of Participants Developing a Serum Anti-rotavirus Immunoglobulin (Ig) A Titer of 20 or Greater in the 89-12 IgA Assay

  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA 89-12 assay to determine the anti-rotavirus IgA antibody titer. A participant met the threshold of a positive response if the post vaccination anti-rotavirus IgA antibody titier was 20 or greater.

  3-6 weeks after the last vaccination

• Geometric Mean Serum Anti-rotavirus IgA Titer

  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA assay to determine the anti-rotavirus IgA antibody titers. The geometric mean titers (GMT) for each group were calculated along with the 95% confidence intervals.

  3-6 weeks after the last dose of vaccine

Secondary Outcomes (6)

• GMT of Neutralizing Rotavirus Antibody to the Most Common Rotavirus Serotypes (G1-G4 and G9)

  3-6 weeks after the last dose of vaccine.

• Number of Participants Experiencing Solicited Systemic Reactions in the 8 Days After Vaccination

  Days 1-8 after each vaccination

• Number of Participants Experiencing Hematochezia at Any Time During the Study

  Day 1 through 6 months after the last vaccination

• Number of Participants Developing Neutralizing Rotavirus Antibody to Rotavirus Serotypes G1, G2, G4P6 and G9

  3-6 weeks after the last dose of vaccine.

• Number of Participants Developing Neutralizing Rotavirus Antibody to Rotavirus Serotype G3

  3-6 weeks after the last dose of vaccine.

Study Arms (5)

Group 1, RotaTeq® x 3

ACTIVE COMPARATOR

2, 4 and 6 months of age: RotaTeq®

Biological: RotaTeq®

Group 5, Rotarix®, RotaTeq® x2

EXPERIMENTAL

2 months of age: Rotarix®; 4 and 6 months of age: RotaTeq®

Biological: Rotarix®; Biological: RotaTeq®

Group 4, Rotarix® x 2

ACTIVE COMPARATOR

2 and 4 months of age: Rotarix®

Biological: Rotarix®

Group 2, RotaTeq®, Rotarix® x 2

EXPERIMENTAL

2 months of age: RotaTeq®; 4 and 6 months of age: Rotarix®

Biological: Rotarix®; Biological: RotaTeq®

Group 3, RotaTeq® x 2, Rotarix®

EXPERIMENTAL

2 and 4 months of age: RotaTeq®; 6 months of age: Rotarix®

Biological: Rotarix®; Biological: RotaTeq®

Interventions

Rotarix® BIOLOGICAL

Each 1-mL dose of Rotarix® contains a suspension of at least 10\^6 median Cell Culture Infective Dose (CCID50) of live, attenuated human G1P rotavirus after reconstitution. The lyophilized vaccine contains amino acids, dextran, Dulbecco's Modified Eagle Medium (DMEM), sorbitol, and sucrose. The liquid diluent contains calcium carbonate, sterile water, and xanthan. The diluent includes an antacid component (calcium carbonate) to protect the vaccine during passage through the acid environment of the stomach. Rotarix® contains no preservatives. Once reconstituted, the vaccine will appear white and turbid.

Group 2, RotaTeq®, Rotarix® x 2; Group 3, RotaTeq® x 2, Rotarix®; Group 4, Rotarix® x 2; Group 5, Rotarix®, RotaTeq® x2

RotaTeq® BIOLOGICAL

2-mL ready-to-use oral solution of live reassortant rotaviruses, containing G1, G2, G3, G4, and P1A, which contains a minimum of 2.0 to 2.8 x 10\^6 infectious units (IU) per individual reassortant dose, depending on the serotype, and not greater than 116 x 10\^6 IU per aggregate dose. The buffered stabilizer solution contains sucrose, sodium citrate, sodium phosphate monobasic monohydrate, sodium hydroxide, polysorbate 80, cell culture media, and trace amounts of fetal bovine serum. RotaTeq® contains no preservatives. RotaTeq® is a pale yellow clear liquid that may have a pink tint.

Group 1, RotaTeq® x 3; Group 2, RotaTeq®, Rotarix® x 2; Group 3, RotaTeq® x 2, Rotarix®; Group 5, Rotarix®, RotaTeq® x2

Eligibility Criteria

• Age: 6 Weeks - 14 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Male or female infants who are at least 6 weeks of age and no more than 14 weeks, 6 days of age at Visit 1.
• Parent(s)/legal guardian(s) have signed informed consent documents.
• Children who will be available for the entire study period and whose parents/legal guardians can be reached by telephone.
• Healthy infants as determined by medical history and by a baseline physical examination with no clinically significant abnormal findings within 14 days before the first dose.
• Parents/legal guardians able to complete all relevant study procedures during study participation.

You may not qualify if:

• Any clinically significant history of gastrointestinal disease including abdominal surgery or liver disease or other serious medical conditions as determined by the site investigator.
• Any history of immunodeficiency in the infant (e.g., the infant is known to be human immunodeficiency virus (HIV) positive, to have hypogammaglobulinemia, or to have an underlying malignancy), or any infant with any unvaccinated household contact who is immunocompromised such as:
• Any malignancies or are otherwise immunocompromised;
• Primary immunodeficiency; or
• Receiving immunosuppressive therapy.
• Known sensitivity to any vaccine components, such as latex in the Rotarix® applicator.
• Previous receipt of a rotavirus vaccine.
• Acute illness at the time of vaccine administration, such as any of the following within the past 48 hours:
• Axillary temperature of 100.4 degrees Fahrenheit or higher, or
• More than 3 grossly watery stools, or
• Any episodes of vomiting (forceful expulsion of partially digested milk/food). Infants with previous diagnoses of gastroesophageal reflux whose regurgitation episodes have not changed in the 48-hour period prior to the first vaccination may be enrolled.
• The subject is currently participating in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study.
• Less than 37 weeks gestation at birth.
• Receipt of blood and/or blood products (including immunoglobulin) within 4 weeks before vaccine administration.
• The subject has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (13)

Kaiser Permanente Vaccine Study Center

Oakland, California, 94612-3610, United States

Location

Children's Hospital & Research Center Oakland - Primary Care Clinic

Oakland, California, 94618-1033, United States

Location

Emory Children's Center - Pediatric Infectious Diseases

Atlanta, Georgia, 30322-1014, United States

Location

University of Iowa - Vaccine Research & Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

Baltimore, Maryland, 21201-1509, United States

Location

Children's Mercy Hospital and Clinics - Infectious Diseases

Kansas City, Missouri, 64108-4619, United States

Location

Duke Translational Medicine Institute - Clinical Vaccine Unit

Durham, North Carolina, 27704-2120, United States

Location

Primary Physicians Research Inc. - Pittsburgh

Pittsburgh, Pennsylvania, 15241-3100, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

The University of Texas Medical Branch - Sealy Center for Vaccine Development (SCVD)

Galveston, Texas, 77555-1121, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Group Health Research Institute - Seattle

Seattle, Washington, 98101-1466, United States

Location

Seattle Children's Hospital - Infectious Diseases

Seattle, Washington, 98105-3901, United States

Location

Related Publications (1)

• Libster R, McNeal M, Walter EB, Shane AL, Winokur P, Cress G, Berry AA, Kotloff KL, Sarpong K, Turley CB, Harrison CJ, Pahud BA, Marbin J, Dunn J, El-Khorazaty J, Barrett J, Edwards KM; VTEU Rotavirus Vaccine Study Work Group. Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules. Pediatrics. 2016 Feb;137(2):e20152603. doi: 10.1542/peds.2015-2603. Epub 2016 Jan 28.

  PMID: 26823540 DERIVED

MeSH Terms

Conditions

Rotavirus Infections; Gastroenteritis

Interventions

RIX4414 vaccine; RotaTeq

Condition Hierarchy (Ancestors)

Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Gastrointestinal Diseases; Digestive System Diseases

Results Point of Contact

• Title: Kathryn M. Edwards, MD
• Organization: Vanderbilt University Medical Center

kathryn.edwards@vanderbilt.edu

615-322-3078

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: December 24, 2010
• Study Start: March 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: March 1, 2014
• Last Updated: October 28, 2014
• Results First Posted: October 28, 2014

Record last verified: 2014-09

Locations

US (13)