Safety and Immune Response of a Rotavirus Vaccine in HIV-infected and Uninfected Children Born to HIV-infected Mothers
Safety and Immunogenicity of a Live, Attenuated Rotavirus Vaccine (RotaTeq™) in HIV-1 Infected and Uninfected Children Born to HIV-1-Infected Mothers
3 other identifiers
interventional
202
4 countries
6
Brief Summary
Rotavirus is the leading cause of severe diarrhea in infants and young children, accounting for 45% of severe diarrhea disease in both developed and developing countries. Annually, rotavirus causes approximately 111 million episodes of gastroenteritis requiring home care, 25 million clinic visits, 2 million hospitalizations, and approximately 440,000 deaths in children less than 5 years of age, of which approximately 90% of hospitalizations and 99% of deaths occur in developing countries. Although rotavirus infection is not more common in HIV-infected children, it complicates their care and interferes with their nutrition. Chances of death by these infections can be greater in HIV-infected children when they also suffer from wasting, malnutrition, and/or opportunistic infections. The primary purpose of this study was to evaluate the safety and immunogenicity of the Rotavirus vaccine candidate, RotaTeq, in HIV-infected and uninfected children born to HIV-infected mothers.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2009
Typical duration for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 10, 2009
CompletedFirst Posted
Study publicly available on registry
April 14, 2009
CompletedStudy Start
First participant enrolled
December 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2014
CompletedResults Posted
Study results publicly available
July 22, 2015
CompletedNovember 5, 2021
July 1, 2015
4.1 years
April 10, 2009
June 22, 2015
November 3, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants Developing New Grade >=3 Adverse Events
Percentage of participants developing new grade \>=3 adverse events (abnormal laboratory values (hematology and chemistry), signs, symptoms and diagnoses) not present at the time of the first vaccination. Adverse events were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Version 1.0, December 2004, Clarification August 2009).
From study entry until at least 42 days after third vaccination
Percentage of Participants Classified as Responders as Measured by Serum Anti-rotavirus IgA ELISA (IgA) and Serum Neutralizing Antibodies (SNA) G1, G2, G3, G4 and P1.
Percentage of participants who experienced \>=3-fold increases from prior to the first vaccination to at least 14 days after the third vaccination in Iga, SNA G1, SNA G2, SNA G3, SNA G4 and SNA P1.
Prior to first vaccination and at least 14 days after third vaccination
Secondary Outcomes (5)
Number of Participants With Fecal Shedding of RotaTeq Strains After Each Vaccination
At entry, days 7, 14, 21 and 42 days after first dose, and at days 7 and 21 after the second and third doses
Percentage of HIV-1 Infected Participants With HIV-1 RNA <= 400 Copies/ml
42 days after third vaccination or last study visit with an HIV-1 RNA measurement
Change in CD4 Percent From Entry to Last Study Visit in HIV-1 Infected Participants
At entry and 42 days after third vaccination or last study visit with CD4 measurement
Change in CD4 Count From Entry to Last Study Visit in HIV-1 Infected Participants
At entry and 42 days after third vaccination or last study visit with CD4 measurement
Number of Participants Classified at Screening or Entry as HIV-1 Uninfected, and Acquiring HIV-1 Infection on Study
From study entry until at least 42 days after third vaccination
Study Arms (4)
HIV-uninfected RotaTeq
EXPERIMENTALHIV-1 uninfected participants receiving 3 doses of RotaTeq vaccine at intervals of 4-10 weeks with the third dose administered by 32 weeks of age.
HIV-uninfected Placebo
PLACEBO COMPARATORHIV-1 uninfected participants receiving 3 doses of placebo at intervals of 4-10 weeks with the third dose administered by 32 weeks of age
HIV-infected RotaTeq
EXPERIMENTALHIV-1 infected participants receiving 3 doses of RotaTeq vaccine at intervals of 4-10 weeks with the third dose administered by 32 weeks of age.
HIV-1 infected Placebo
PLACEBO COMPARATORHIV-1 infected participants receiving 3 doses of placebo at intervals of 4-10 weeks with the third dose administered by 32 weeks of age
Interventions
2 mL solution of live reassortant rotaviruses, containing G1, G2, G3, G4 and P1A which contains a minimum of 2.0 - 2.8 x 10\^6 infectious units (IU) per individual reassortant dose, depending on the serotype, and not greater than 116 x 10\^6 IUs per aggregate dose
Eligibility Criteria
You may qualify if:
- Participant was born to an HIV-1-infected mother whose HIV-1 diagnosis was determined by two different tests performed on the same or separate maternal samples obtained before or during pregnancy or during the post-partum period. Acceptable tests are antibodies in serum or saliva, HIV RNA or DNA, or antigen in the blood.
- Presence or absence of HIV RNA or DNA in the blood of the infant
- CD4% documented at screening
- Parent or legal guardian agreed to give written informed consent and was willing to comply with study requirements
- Parents/guardians of each participant stated their willingness to have the child follow the country-specific childhood Expanded Programme on Immunization ("EPI") schedule for concomitant childhood vaccines recommended during the study period
- HIV-infected participants had initiated antiretroviral therapy (ART) before or at the time of administration of the first dose of study vaccine/placebo. Note: It was not acceptable for participants to take a prescription home with them to start ART on the day of vaccination.
- Successful administration of first vaccine (for second vaccination) and second vaccine (for third vaccination)
- Participants were less than 32 weeks of age at the time of the third vaccine/placebo dose
You may not qualify if:
- Concurrent participation in any study of an investigational drug or vaccine, except for studies for prevention of perinatal HIV-1 transmission
- Known allergy to any component of the study vaccine
- Active gastrointestinal illness or fever. Fever was defined as greater than or equal to 38.5º C in accordance with WHO guidelines for administration of childhood vaccines.
- Could not be enrolled from any site at which rotavirus vaccine was available and was being administered
- Any condition, which would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
- Any other condition, situation, or clinically significant finding (other than HIV infection) that, in the investigator's opinion, would interfere with study participation, or interpretation
- Participants with a known history of Severe Combined Immunodeficiency (SCID) or intussusception
- \- Any Grade 4 adverse events believed to be possibly/probably/definitely related to vaccine would disqualify subjects from receiving additional doses. Grade 3 adverse events believed to be possibly/probably related to vaccine had to be demonstrated to have improved to less than Grade 2 prior to receiving the next scheduled dose.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Gaborone CRS
Gaborone, Botswana
Molepolole CRS
Gaborone, Botswana
Kilimanjaro Christian Medical Center CRS
Moshi, Tanzania
George CRS
Lusaka, Zambia
Harare Family Care CRS
Harare, Zimbabwe
Parirenyatwa CRS
Harare, Zimbabwe
Related Publications (4)
Committee on Infectious Diseases; American Academy of Pediatrics. Prevention of rotavirus disease: updated guidelines for use of rotavirus vaccine. Pediatrics. 2009 May;123(5):1412-20. doi: 10.1542/peds.2009-0466. Epub 2009 Mar 30.
PMID: 19332437BACKGROUNDKiulia NM, Nyaundi JK, Peenze I, Nyachieo A, Musoke RN, Steele AD, Mwenda JM. Rotavirus infections among HIV-infected children in Nairobi, Kenya. J Trop Pediatr. 2009 Oct;55(5):318-23. doi: 10.1093/tropej/fmp016. Epub 2009 Mar 10.
PMID: 19276145BACKGROUNDParashar UD, Glass RI. Rotavirus vaccines--early success, remaining questions. N Engl J Med. 2009 Mar 12;360(11):1063-5. doi: 10.1056/NEJMp0810154. No abstract available.
PMID: 19279338BACKGROUNDLevin MJ, Lindsey JC, Kaplan SS, Schimana W, Lawrence J, McNeal MM, Bwakura-Dangarembizi M, Ogwu A, Mpabalwani EM, Sato P, Siberry G, Nelson M, Hille D, Weinberg GA, Weinberg A. Safety and immunogenicity of a live attenuated pentavalent rotavirus vaccine in HIV-exposed infants with or without HIV infection in Africa. AIDS. 2017 Jan 2;31(1):49-59. doi: 10.1097/QAD.0000000000001258.
PMID: 27662551DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The study was closed to enrollment prematurely so statistical power to detect differences was reduced.
Results Point of Contact
- Title
- Melissa Allen, Director, IMPAACT Operations Center
- Organization
- Family Health International (FHI 360)
Study Officials
- STUDY CHAIR
Myron J. Levin, MD
University of Colorado at Denver Health Sciences Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 10, 2009
First Posted
April 14, 2009
Study Start
December 1, 2009
Primary Completion
January 1, 2014
Study Completion
January 1, 2014
Last Updated
November 5, 2021
Results First Posted
July 22, 2015
Record last verified: 2015-07