Safety and Immune Response of a Rotavirus Vaccine in HIV-infected and Uninfected Children Born to HIV-infected Mothers

Condition(s) targeted: HIV Infections

Intervention: RotaTeq vaccine (Biological); RotaTeq vaccine placebo (Biological)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Myron J. Levin, MD, Study Chair, Affiliation: University of Colorado at Denver Health Sciences Center

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. 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 is to evaluate the safety and immunogenicity of the Rotavirus vaccine candidate, RotaTeq, in HIV-infected and uninfected children born to HIV-infected mothers.

Official title: Safety and Immunogenicity of a Live, Attenuated Rotavirus (RotaTeq™) in HIV-1 Infected and Uninfected Children Born to HIV-1-Infected Mothers

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Safety of any dose of RotaTeq given to HIV-1-infected children born to HIV-1-infected mothers

Immunogenicity of 3-dose regimen of RotaTeq in HIV-1-infected and uninfected children born to HIV-1-infected mothers

Secondary outcome:

Fecal shedding of RotaTeq strains after each dose

Relationship between anti-rotavirus serologic immune responses to CD4 count and/or CD4%, plasma RNA or DNA, and antiretroviral therapy after a 3-dose regimen of RotaTeq given to HIV-1-infected children born to HIV-1-infected mothers

Incidence of HIV infection

Relationship between virus shedding and rotavirus-specific SNA antibodies, copro-antibodies, and CMI against rotavirus vaccine serotypes in recipients of the rotavirus vaccine

IgA and IgG copro-antibodies and CMI responses against rotavirus serotypes contained in the vaccine in HIV-1-infected versus uninfected infants born to HIV-1-infected mothers

CD4% in HIV-1-infected recipients of rotavirus vaccine or placebo

Changes in microbial translocation in response to vaccination with RotaTeq relative to placebo in HIV-1-infected and uninfected participants

Relationship of mucosal and cell-mediated immune responses to CD4 counts and/or CD4%, plasma HIV RNA or DNA, and ART after 3-dose regimen of RotaTeq given to HIV-1-infected children

Detailed description: 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. The primary purpose of this study is to evaluate the safety and immunogenicity of the Rotavirus vaccine candidate, RotaTeq, in HIV-infected and uninfected children born to HIV-infected mothers.

This study will last up to 18 weeks. Participants will be placed in either Group 1 or 2.

Participants in Group 1 will be HIV-uninfected. Participants in Arm 1A will receive 3 doses of the study vaccine over a 12-week period. Participants in Arm 1B will receive 3 doses of study vaccine placebo over a 12-week period.

Participants in Group 2 will be HIV-infected. Participants in Arm 2A will have CD4 percentages of at least 20% and receive 3 doses of the study vaccine over a 12-week period. Participants in Arm 2B will have CD4 percentages 15 up to 20% and receive 3 doses of study vaccine placebo over a 12-week period. Participants in Arm 2C will have CD4 percentages

between 15 - 24% and receive 3 doses of the study vaccine over a 12-week period.

Participants in Arm 2D will have CD4 percentages between 15 - 24% and receive 3 doses of

study vaccine placebo over a 12-week period. Participants in Arm 2E will have CD4 percentages less than 15% and receive 3 doses of the study vaccine over a 12-week period. Participants in Arm 2F will have CD4 percentages less than 15% and receive 3 doses of study vaccine placebo over a 12-week period.

There will be 16 study visits for each participant. They will occur at screening and Days 0, 7, 14, 21, 42, 49, 56, 63, 70, 91, 98, 105, 112, 119, and 140. Study vaccinations will occur on Days 0, 49, and 98. Stool samples will be collected at most visits. Blood collection will occur at select visits.

For any missed visits, study staff will contact participants' caregivers and conduct a study visit at the participant's home, if possible.

If a national recommendation for rotavirus vaccine is implemented at a study site, participants who are receiving the placebo vaccine will be discontinued from the study and will receive the rotavirus vaccine, per site procedures.

Minimum age: N/A. Maximum age: 14 Weeks. Gender(s): Both.

Criteria:

Inclusion Criteria for All Steps:

- 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% is documented at screening

- Parent or legal guardian agrees to give written informed consent and is willing to

comply with study requirements

- Parents/guardians of each participant must state 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

Inclusion Criteria for Steps 2 and 3:

- Successful administration of first vaccine (for Step 2) and second vaccine (for Step

3)

Exclusion Criteria for All Steps:

- 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 is defined as greater than or equal

to 38. 5º C in accordance with WHO guidelines for administration of childhood vaccines.

- Cannot be enrolled from any site at which rotavirus vaccine is available and is being

administered

- Any condition, including intussusception, which would, in the opinion of the site

investigator, place the participant at an unacceptable risk of injury or render them unable to meet the requirements of the study

- Any other condition (including known history of severe combined immunodeficiency

disease [SCID]), situation, or clinically significant finding (other than HIV infection) that, in the investigator's opinion, would interfere with study participation, or interpretation

Exclusion Criteria for Steps 2 and 3:

- Any Grade 4 adverse events believed to be possibly/probably related to vaccine will

disqualify subjects from receiving additional doses. Grade 3 adverse events believed to be possibly/probably related to vaccine must be demonstrated to have improved to less than Grade 2 prior to receiving the next scheduled dose.

Gaborone Prevention/Treatment Trials CRS, Gaborone, Botswana; Recruiting
Tebogo Kakhu, Phone: 267-393-0335, Email: tkakhu@bhp.org.bw
Anthony Ogwu, MD, Principal Investigator

Molepolole Prevention/Treatment Trials CRS, Molepolole, Botswana; Recruiting
Evans Moko, Phone: 267-592-1013, Email: emoko@bhp.org.bw
Aida Asmelash, MD, MPH, Principal Investigator

Related publications:

Committee on Infectious Diseases. Prevention of Rotavirus Disease: Updated Guidelines for Use of Rotavirus Vaccine. Pediatrics. 2009 Mar 30; [Epub ahead of print]

Kiulia 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 Mar 18; [Epub ahead of print]

Parashar UD, Glass RI. Rotavirus vaccines--early success, remaining questions. N Engl J Med. 2009 Mar 12;360(11):1063-5. No abstract available.

Starting date: December 2009
Last updated: September 8, 2010