HIV InfectionsNCT00099658
Safety of and Immune Response to a Pneumococcal Vaccine (PncCV) in HIV Infected and Uninfected Children
A study testing Pneumococcal polysaccharide-protein conjugate vaccine in people with HIV Infections and Pneumococcal Infections, run by CIPRA SA.
Trial summary
Infection by Streptococcal pneumoniae is a common invasive bacterial infection in HIV infected children. The purpose of this study is to determine the safety of and immune response to a pneumococcal polysaccharide-protein conjugate vaccine (PncCV) in HIV infected and uninfected children. Read more about this study
- Who is it for?
- Ages 4 to 10 weeksHealthy volunteers can take part
- Conditions the study is for
- HIV Infections, Pneumococcal Infections
- What is being tested?
- Pneumococcal polysaccharide-protein conjugate vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 579 participants
- Where
- No sites listed yet
- Study dates
- Apr 2005to Jun 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 10 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Birth weight of at least 2 kg (4.4 lbs)
- Written informed consent from parent or guardian
- Mother's HIV status documented after 24th week of pregnancy, if her infant joins Group 5 and is HIV uninfected
- Parent or guardian of infant intends to remain in the study area for the duration of the trial
- HIV infected
- Participating in CIPRA SA-Project 2
Who cannot join
- Blood products prior to study entry
- Immunosuppressant agents for more than 2 weeks, within 1 week of study entry
- Unable to tolerate oral medications
- Presence of any major, life-threatening congenital defect
- Acute illness or fever requiring hospitalization within 72 hours of immunization
- Grade 2 vaccine-related allergic reaction
Show all 11Show fewer
- Grade 3 or 4 clinical or laboratory toxicity related to vaccination
- Use of any antiretroviral therapies other than those allowed in CIPRA SA-Project 2. Infants who received antiretroviral drugs used to prevent mother-to-infant HIV transmission are eligible for this study.
- Use of investigational drugs, systemic cytotoxic chemotherapy, or interleukin or other immune modulators
- Require certain medications
- Vaccines prior to study entry. Infants who have received bacille Calmette-Guerin or oral polio vaccines are not excluded.
About this study
Official title: Evaluation of Quantitative and Qualitative Antibody Responses to Streptococcus Pneumoniae and Haemophilus Influenzae Type b Conjugate Vaccines Amongst HIV-1-Exposed-Infected Children That Are Receiving Vs. Those Not Receiving Antiretroviral Therapy, as Well as Among HIV-1-Exposed-Uninfected Children and HIV-1-Unexposed-Uninfected Children
Infection by Streptococcal pneumoniae is a common invasive bacterial infection in HIV infected children. The purpose of this study is to determine the safety of and immune response to a pneumococcal polysaccharide-protein conjugate vaccine (PncCV) in HIV infected and uninfected children. The study will also determine the safety of and immune response to Haemophilus influenzae vaccine (HibCV) in these children. Recruitment for this study will occur at two hospitals in South Africa, and all HIV infected infants participating in this study must also be coenrolled in the CIPRA SA-Project 2 study.
Read the detailed description
HIV infected children are at high risk for invasive pneumococcal disease (IPD) caused by the bacterium Streptococcus pneumoniae. Chemoprophylaxis has been used in children with certain diseases for the prevention of IPD, but drug resistance may develop with this prevention strategy. In contrast, a vaccine to prevent IPD would have fewer negative implications on future treatment options than chemoprophylaxis. This study will evaluate the safety of and immune response to PncCV in South African HIV infected and uninfected children. This study will also evaluate the safety of and immune response to HibCV in these children.
This study will last 5.5 years. There will be 5 groups in this study. Group 1 will be HIV uninfected infants born to HIV uninfected mothers. Group 2 will be HIV infected infants in CDC Disease Category 1 who were randomly assigned to the delayed therapy arm (Arm 1) of CIPRA SA-Project 2. Group 3 will be HIV infected infants in CDC Disease Category 1 who were randomly assigned to the first early therapy arm (Arm 2) of CIPRA SA-Project 2. Group 4 will be HIV infected infants in CDC Disease Category 2 or 3 who were randomly assigned to the second early therapy arm (Arm 3) of CIPRA SA-Project 2. Group 5 will be HIV uninfected infants born to HIV infected mothers; Group 5 infants will undergo repeat HIV testing at 4 to 8 months of age, 9 to 11 months of age, and approximately 18 months of age.
There will be 13 study visits; medical history assessment, a physical examination, and blood collection will occur at each visit. At each of 3 study visits before age 24 weeks, all participants will receive an injection of PncCV and an injection of routine pediatric vaccines, including HibCV. Previously vaccinated HIV infected participants will only receive those vaccines they need to complete the South African series of routine pediatric vaccinations. Within each group, participants will be randomly assigned to receive a booster shot of either PncCV or HibCV between 64 and 76 weeks of age. Participants will also receive two measles vaccinations between 38 and 76 weeks of age. Parents or guardians will be asked to complete a diary card after each vaccination and report any adverse effects occurring within the 72 hours post-vaccination.
- Conditions
- HIV Infections, Pneumococcal Infections
- Being tested
- Pneumococcal polysaccharide-protein conjugate vaccine
- Keywords
- MTCT
- Medical subject headings
- HIV Infections, Pneumococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pneumococcal polysaccharide-protein conjugate vaccineBiological
Also called PncCV
Injection administered three times before the age of 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | HIV-uninfected infants born to HIV-uninfected mothers Receives: Biological: Pneumococcal polysaccharide-protein conjugate vaccine |
| 2 | Experimental | HIV-infected infants in CDC Disease Category 1 who were randomly assigned to the delayed therapy arm (Arm 1) of CIPRA SA-Project 2 Receives: Biological: Pneumococcal polysaccharide-protein conjugate vaccine |
| 3 | Experimental | HIV-infected infants in CDC Disease Category 1 who were randomly assigned to the first early therapy arm (Arm 2) of CIPRA SA-Project 2 Receives: Biological: Pneumococcal polysaccharide-protein conjugate vaccine |
| 4 | Experimental | HIV-infected infants in CDC Disease Category 2 or 3 who were randomly assigned to the second early therapy arm (Arm 3) of CIPRA SA-Project 2 Receives: Biological: Pneumococcal polysaccharide-protein conjugate vaccine |
| 5 | Experimental | HIV-uninfected infants born to HIV infected mothers Receives: Biological: Pneumococcal polysaccharide-protein conjugate vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate to PncCV among children in Group 2 compared to those in Groups 1 and 3
Measured: At Weeks 3 and 6
Response rate to PncCV among children in Group 2 compared to those in Groups 1 and 3 before receiving booster vaccine dose
Measured: At Weeks 64 through 76
Vaccine safety profiles after each of the three primary doses of PncCV and booster doses of PncCV and HibCV
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2004 (estimated)
- Study startApr 2005
- Primary completionDec 2013 (estimated)
- Study completionJun 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 579 participants (actual)
Sponsor and investigators
- Lead sponsor
- CIPRA SA
- Sponsor type
- Research network
- Investigators
- Shabir Madhi, MD, MBBCH, Mmed, FCPaeds, PhD, Study chair, Chris Hani Baragwanath Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00099658
- Sponsor's protocol ID
- CIPRA-SA Project 4
- Other IDs
- U19AI053217, CIPRA, Project 4
- Status last verified
- Feb 2011
- First submitted
- 17 Dec 2004
- Last updated
- 15 Feb 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce N; Vaccine Trialists Group. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med. 2003 Oct 2;349(14):1341-8. doi: 10.1056/NEJMoa035060.
PubMed 14523142Madhi SA, Kuwanda L, Cutland C, Holm A, Kayhty H, Klugman KP. Quantitative and qualitative antibody response to pneumococcal conjugate vaccine among African human immunodeficiency virus-infected and uninfected children. Pediatr Infect Dis J. 2005 May;24(5):410-6. doi: 10.1097/01.inf.0000160942.84169.14.
PubMed 15876939Madhi SA, Petersen K, Madhi A, Khoosal M, Klugman KP. Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children. Clin Infect Dis. 2000 Jul;31(1):170-6. doi: 10.1086/313925. Epub 2000 Jul 25.
PubMed 10913417Nachman S, Kim S, King J, Abrams EJ, Margolis D, Petru A, Shearer W, Smith E, Moye J, Blanchard S, Hawkins E, Bouquin P, Vink P, Benson M, Estep S, Malinoski F; Pediatric AIDS Clinical Trials Group Study 292 Team. Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants with human immunodeficiency virus type 1 infection. Pediatrics. 2003 Jul;112(1 Pt 1):66-73. doi: 10.1542/peds.112.1.66.
PubMed 12837869Pai VB, Heyneman CA, Erramouspe J. Conjugated heptavalent pneumococcal vaccine. Ann Pharmacother. 2002 Sep;36(9):1403-13. doi: 10.1345/aph.1A048.
PubMed 12196061Mutsaerts EAML, Nunes MC, van Rijswijk MN, Klipstein-Grobusch K, Otwombe K, Cotton MF, Violari A, Madhi SA. Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children. Clin Infect Dis. 2019 Aug 1;69(4):687-696. doi: 10.1093/cid/ciy964.
PubMed 30418528Madhi SA, Izu A, Nunes MC, Violari A, Cotton MF, Jean-Philippe P, Klugman KP, von Gottberg A, van Niekerk N, Adrian PV; CIPRA 4 team. Longitudinal study on Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV-infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine. Vaccine. 2015 May 28;33(23):2662-9. doi: 10.1016/j.vaccine.2015.04.024. Epub 2015 Apr 21.
PubMed 25910923
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Quantitative and Qualitative Antibody Responses to Streptococcus Pneumoniae and Haemophilus Influenzae Type b Conjugate Vaccines Amongst HIV-1-Exposed-Infected Children That Are Receiving Vs. Those Not Receiving Antiretroviral Therapy, as Well as Among HIV-1-Exposed-Uninfected Children and HIV-1-Unexposed-Uninfected Children
- ClinicalTrials.gov ID
- NCT00099658
- Acronym / sponsor ID
- CIPRA-SA Project 4
- Conditions
- HIV Infections, Pneumococcal Infections
- Keywords
- MTCT
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 579 participants (actual)
- Lead sponsor
- CIPRA SAResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Apr 2005
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Jun 2014 (estimated)
- First posted
- 20 Dec 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Infection by Streptococcal pneumoniae is a common invasive bacterial infection in HIV infected children. The purpose of this study is to determine the safety of and immune response to a pneumococcal polysaccharide-protein conjugate vaccine (PncCV) in HIV infected and uninfected children. The study will also determine the safety of and immune response to Haemophilus influenzae vaccine (HibCV) in these children. Recruitment for this study will occur at two hospitals in South Africa, and all HIV infected infants participating in this study must also be coenrolled in the CIPRA SA-Project 2 study.
Detailed description
HIV infected children are at high risk for invasive pneumococcal disease (IPD) caused by the bacterium Streptococcus pneumoniae. Chemoprophylaxis has been used in children with certain diseases for the prevention of IPD, but drug resistance may develop with this prevention strategy. In contrast, a vaccine to prevent IPD would have fewer negative implications on future treatment options than chemoprophylaxis. This study will evaluate the safety of and immune response to PncCV in South African HIV infected and uninfected children. This study will also evaluate the safety of and immune response to HibCV in these children.
This study will last 5.5 years. There will be 5 groups in this study. Group 1 will be HIV uninfected infants born to HIV uninfected mothers. Group 2 will be HIV infected infants in CDC Disease Category 1 who were randomly assigned to the delayed therapy arm (Arm 1) of CIPRA SA-Project 2. Group 3 will be HIV infected infants in CDC Disease Category 1 who were randomly assigned to the first early therapy arm (Arm 2) of CIPRA SA-Project 2. Group 4 will be HIV infected infants in CDC Disease Category 2 or 3 who were randomly assigned to the second early therapy arm (Arm 3) of CIPRA SA-Project 2. Group 5 will be HIV uninfected infants born to HIV infected mothers; Group 5 infants will undergo repeat HIV testing at 4 to 8 months of age, 9 to 11 months of age, and approximately 18 months of age.
There will be 13 study visits; medical history assessment, a physical examination, and blood collection will occur at each visit. At each of 3 study visits before age 24 weeks, all participants will receive an injection of PncCV and an injection of routine pediatric vaccines, including HibCV. Previously vaccinated HIV infected participants will only receive those vaccines they need to complete the South African series of routine pediatric vaccinations. Within each group, participants will be randomly assigned to receive a booster shot of either PncCV or HibCV between 64 and 76 weeks of age. Participants will also receive two measles vaccinations between 38 and 76 weeks of age. Parents or guardians will be asked to complete a diary card after each vaccination and report any adverse effects occurring within the 72 hours post-vaccination.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: Pneumococcal polysaccharide-protein conjugate vaccineHIV-uninfected infants born to HIV-uninfected mothers |
| 2 | Experimental | Biological: Pneumococcal polysaccharide-protein conjugate vaccineHIV-infected infants in CDC Disease Category 1 who were randomly assigned to the delayed therapy arm (Arm 1) of CIPRA SA-Project 2 |
| 3 | Experimental | Biological: Pneumococcal polysaccharide-protein conjugate vaccineHIV-infected infants in CDC Disease Category 1 who were randomly assigned to the first early therapy arm (Arm 2) of CIPRA SA-Project 2 |
| 4 | Experimental | Biological: Pneumococcal polysaccharide-protein conjugate vaccineHIV-infected infants in CDC Disease Category 2 or 3 who were randomly assigned to the second early therapy arm (Arm 3) of CIPRA SA-Project 2 |
| 5 | Experimental | Biological: Pneumococcal polysaccharide-protein conjugate vaccineHIV-uninfected infants born to HIV infected mothers |
Who may qualify
- Ages
- 4 to 10 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Birth weight of at least 2 kg (4.4 lbs)
- Written informed consent from parent or guardian
- Mother's HIV status documented after 24th week of pregnancy, if her infant joins Group 5 and is HIV uninfected
- Parent or guardian of infant intends to remain in the study area for the duration of the trial
- HIV infected
Key exclusion criteria (11 listed)
- Blood products prior to study entry
- Immunosuppressant agents for more than 2 weeks, within 1 week of study entry
- Unable to tolerate oral medications
- Presence of any major, life-threatening congenital defect
- Acute illness or fever requiring hospitalization within 72 hours of immunization
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pneumococcal polysaccharide-protein conjugate vaccineAlso: PncCVInjection administered three times before the age of 24 weeks | Biological | 1, 2, 3, 4, 5 |
Primary outcome
Response rate to PncCV among children in Group 2 compared to those in Groups 1 and 3
Time frame: At Weeks 3 and 6
Response rate to PncCV among children in Group 2 compared to those in Groups 1 and 3 before receiving booster vaccine dose
Time frame: At Weeks 64 through 76
Vaccine safety profiles after each of the three primary doses of PncCV and booster doses of PncCV and HibCV
Time frame: Throughout study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2011.
- Background: PubMed 14523142Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce N; Vaccine Trialists Group. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med. 2003 Oct 2;349(14):1341-8. doi: 10.1056/NEJMoa035060.
- Background: PubMed 15876939Madhi SA, Kuwanda L, Cutland C, Holm A, Kayhty H, Klugman KP. Quantitative and qualitative antibody response to pneumococcal conjugate vaccine among African human immunodeficiency virus-infected and uninfected children. Pediatr Infect Dis J. 2005 May;24(5):410-6. doi: 10.1097/01.inf.0000160942.84169.14.
- Background: PubMed 10913417Madhi SA, Petersen K, Madhi A, Khoosal M, Klugman KP. Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children. Clin Infect Dis. 2000 Jul;31(1):170-6. doi: 10.1086/313925. Epub 2000 Jul 25.
- Background: PubMed 12837869Nachman S, Kim S, King J, Abrams EJ, Margolis D, Petru A, Shearer W, Smith E, Moye J, Blanchard S, Hawkins E, Bouquin P, Vink P, Benson M, Estep S, Malinoski F; Pediatric AIDS Clinical Trials Group Study 292 Team. Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants with human immunodeficiency virus type 1 infection. Pediatrics. 2003 Jul;112(1 Pt 1):66-73. doi: 10.1542/peds.112.1.66.
- Background: PubMed 12196061Pai VB, Heyneman CA, Erramouspe J. Conjugated heptavalent pneumococcal vaccine. Ann Pharmacother. 2002 Sep;36(9):1403-13. doi: 10.1345/aph.1A048.
- Derived from this study: PubMed 30418528Mutsaerts EAML, Nunes MC, van Rijswijk MN, Klipstein-Grobusch K, Otwombe K, Cotton MF, Violari A, Madhi SA. Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children. Clin Infect Dis. 2019 Aug 1;69(4):687-696. doi: 10.1093/cid/ciy964.
- Derived from this study: PubMed 25910923Madhi SA, Izu A, Nunes MC, Violari A, Cotton MF, Jean-Philippe P, Klugman KP, von Gottberg A, van Niekerk N, Adrian PV; CIPRA 4 team. Longitudinal study on Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV-infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine. Vaccine. 2015 May 28;33(23):2662-9. doi: 10.1016/j.vaccine.2015.04.024. Epub 2015 Apr 21.
- Click here for more information about CIPRA-SA Project 2.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shabir Madhi, MD, MBBCH, Mmed, FCPaeds, PhD study chair
Chris Hani Baragwanath Hospital
Questions about this trial
What is this clinical trial studying?
A study testing Pneumococcal polysaccharide-protein conjugate vaccine in people with HIV Infections and Pneumococcal Infections, run by CIPRA SA.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate to PncCV among children in Group 2 compared to those in Groups 1 and 3 (time frame: At Weeks 3 and 6). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00099658, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2011.