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PNC VaccinePhase 2NCT02717494

Safety and Immunogenicity of Anti-Pneumococcal Vaccines in HIV-Infected Pregnant Women

A Phase 2 study testing PPV-23, PCV-10 and NaCl in people with PNC Vaccine and HIV-infected Pregnant Women, run by Westat at 8 sites in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study was to determine the safety, reactogenicity, immunogenicity, transplacental antibody transfer and interference with infant responses to childhood vaccination of maternal vaccination with pneumococcal conjugate 10-valent vaccine (PCV-10) or pneumococcal polysaccharide 23-valent vaccine… Read more about this study

Who is it for?
Any age, women only
Conditions the study is for
PNC Vaccine, HIV-infected Pregnant Women
What is being tested?
PPV-23, PCV-10 and NaCl
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
347 participants
Where
8 sitesBrazil
Study dates
Mar 2016to May 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Any age
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Step 1 Inclusion Criteria for Pregnant Women:

  1. Pregnant women ≥ 18 years old who provided written informed consent prior to study initiation.
  2. Pregnant women < 18 years old with parent or legal guardian able and willing to provide signed informed consent, or who had the capacity to consent for themselves, as defined by the local Institutional Review Board (IRB), and who provided written informed consent prior to study initiation.
  3. Gestational age [≥ 14 weeks (14 weeks 0 days) to < 33 weeks (32 weeks 6 days)] documented by the approximate date of the last menstrual period and corroborated by ultrasound if obtained as per local standard of care. Results of the ultrasound were recorded on the Abdominal Ultrasound Form.
  4. Documentation of HIV-1 infection defined as positive results from two samples collected at different time points as per standard of care. Results and source documentation may have been obtained from the medical records.
  5. Receipt of HAART (a regimen of at least three ARV drugs) for ≥ 4 weeks prior to enrollment.
  6. Documented platelet count of > 50,000/mm3 and an absolute neutrophil count (ANC) of > 500/ mm3 ≤ 28 days prior to study entry.
  7. Women who were willing and able to comply with the study visits.

Step 1 Exclusion Criteria for Pregnant Women:

  1. Receipt of any PCV or PPV-23 at any time prior to enrollment, documented by medical history or record.
  2. Receipt of any live licensed vaccine ≤ 4 weeks or inactivated licensed vaccine ≤ 2 weeks prior to study entry.
  3. Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 4 weeks prior to enrollment in this study, or expectations to receive another non-licensed agent before delivery unless approval from the protocol team is obtained.
  4. Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 100.4 degrees F ≤ 24 hours prior to study entry.
  5. Women who planed to terminate their pregnancy.
  6. Women who had a prior history of lupus or other autoimmune disorders.
  7. Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study enrollment, or evidence of immunosuppression as a result of an underlying illness (other than HIV-1 infection) or treatment.
  8. Ongoing neoplastic disease (excluding non-melanoma skin cancer, and human papilloma virus-related cervical dysplasia, cervical intraepithelial neoplasia (CIN) grades 1, 2 or 3).
  9. Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) within 12 weeks of study entry.
  10. Women who received last dose of corticosteroids for preterm labor ≤ 1 week prior to study entry. Note: A woman can be enrolled if more than 1 week has elapsed from the last dose of corticosteroids, i.e., enrollment may be delayed to satisfy this criterion.
  11. Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) ≤ 12 weeks prior to enrollment in this study or is scheduled to receive immunoglobulin or other blood products (with the exception of Rho D immune globulin) during pregnancy or for the first 24 weeks after delivery.
  12. Receipt of Interleukin-2 (IL2), interferon (IFN), granulocyte-macrophage colony-stimulating factor (GMCSF) or other immune mediators ≤ 12 weeks before enrollment.
  13. History of a severe adverse reaction to inactivated polysaccharide or conjugated vaccines.
  14. Any condition that 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.
  15. Pregnancy complications (in the current pregnancy) such as pre-term labor, and pre-eclampsia or any other pregnancy related complication, which in the opinion of the investigator might jeopardize the results of the study.
  16. Chronic hepatitis B infection that may require administration of Hepatitis B Hyperimmune Globulin to neonates.

Step 2 Inclusion Criteria for Women:

  1. 24 weeks ± 4 weeks postpartum.
  2. Completion of Step 1.
  3. Receipt of placebo on Step 1.

Step 2 Exclusion Criteria for Women:

  1. Pregnancy.
  2. Receipt of any live licensed vaccine ≤ 4 weeks or inactivated licensed vaccine ≤ 2 weeks prior to Step 2 entry.
  3. Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 4 weeks prior to vaccination, or expects to receive another non-licensed agent within 28 days after vaccination.
  4. Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 100.4 degrees F within 24 hours of entry except when, in the opinion of the physician, withholding the agent entails even greater risk.
  5. Use of anti-cancer systemic chemotherapy or radiation therapy or has developed immunosuppression as a result of an underlying illness (other than HIV-1 infection) or treatment.
  6. Use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) within 2 weeks of entry in Step 2.
  7. Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) within 12 weeks prior to entry in Step 2 or is scheduled to receive immunoglobulin or other blood products (with the exception of Rho D immune globulin) during the 28 days following vaccination.
  8. Receipt of IL2, IFN, GMCSF or other immune mediators ≤ 12 weeks before entry in Step 2.

Step 3 Inclusion Criteria for Women

  1. 24 weeks ± 4 weeks postpartum.
  2. Completion of Step 1.
  3. Receipt of placebo on Step 1.
  4. Met Step 2 exclusion criterion of pregnancy.

Step 3 Exclusion Criteria for Women

None.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Brazil8 sites
  • FUNDEP (Belo Horizonte)

    Belo Horizonte, Minas Gerais, 30130-100

  • Universidade de Caxias do Sul. Brasil

    Caxias do Sul, Rio Grande do Sul, 95070-560

  • Hospital Geral de Nova Iguaçu Avenida Henrique Duque Estrada Mayer

    Nova Iguaçu, Rio de Janeiro, 26030-380

  • Hospital Santa Casa Porto Alegre Brazil

    Porto Alegre, Rio Grande do Sul, 90020-090

  • Hospital Nossa Senhora da Conceicao

    Porto Alegre, Rio Grande do Sul, 91350-200

  • Ribeirão Preto Medical School, University of São Paulo, Brazil

    Ribeirão Preto, São Paulo, 14049-900

  • Instituto de Puericultura e Pediatria Martagao Gesteria

    Rio de Janeiro, Rio de Janeiro, 21 940 590

  • Hospital dos Servidores (Rio de Janeiro)

    Saúde, Rio de Janeiro, 20221-161

Other trials in Brazil

About this study

The purpose of this study was to determine the safety, reactogenicity, immunogenicity, transplacental antibody transfer and interference with infant responses to childhood vaccination of maternal vaccination with pneumococcal conjugate 10-valent vaccine (PCV-10) or pneumococcal polysaccharide 23-valent vaccine (PPV-23) by comparison with placebo.

Read the detailed description

This was a multi-center, Phase II, randomized, double-blinded, placebo-controlled study of Human Immunodeficiency Virus (HIV)-infected pregnant women on Highly Active Antiretroviral Therapy (HAART) who were in the second or third trimester of pregnancy and of their infants. The study was designed to investigate the safety, reactogenicity, immunogenicity, transplacental antibody transfer and interference with infant responses to childhood vaccination of maternal vaccination with PCV-10 or PPV-23 by comparison with placebo.

Mothers were randomized to one of three arms and received PCV-10, PPV-23, or placebo in a blinded fashion. They were followed for safety, immunogenicity and vaccine-specific anti-capsular pneumococcus (PNC) antibody persistence until 24 weeks post-delivery. Women who received placebo were randomized to a second study step and received PCV-10 or PPV-23 at 24 weeks post-delivery. Antibody responses to the vaccine administered 6 months postpartum were measured. Women who received placebo but cannot be randomized to a second study step due to ongoing new pregnancy were enrolled in a third study step and receive open label PCV-10 at the last study visit; no data were collected on these women and they were not followed after vaccine administration. All infants received PCV-10 vaccinations per local standard of care.

Being tested
PPV-23, PCV-10, NaCl
Keywords
PPV-23, PCV-10, HIV, Immunization, Pregnancy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PPV-23Biological

    PPV-23 was a polysaccharide PNC vaccine, licensed in Brazil, directed against 23 serotypes.

  • PCV-10Biological

    PCV-10 was a conjugate PNC vaccine, licensed in Brazil, directed against 10 serotypes.

  • NaClOther

    NaCl was the placebo for the study against which the two vaccines were compared during pregnancy.

Study groups in NCT02717494
Study groupRoleWhat they receive
Arm 1A (PPV-23)ExperimentalIn Step 1, women in Arm 1A were administered a 0.5 milliliter (mL) dose of PPV-23 intramuscularly once.
Receives: Biological: PPV-23
Arm 1B (PCV-10)ExperimentalIn Step 1, women in Arm 1B were administered a 0.5 mL dose of PCV-10 intramuscularly once.
Receives: Biological: PCV-10
Arm 1C (placebo)Placebo comparatorIn Step 1, women in Arm 1C were administered a 0.5 mL dose of 0.9 percent Sodium Chloride (NaCl) intramuscularly once.
Receives: Other: NaCl
Arm 2A (PPV-23)ExperimentalIn Step 2, women who received placebo in step 1 that were randomized to Arm 2A were administered a 0.5 mL dose of PPV-23 intramuscularly once.
Receives: Biological: PPV-23
Arm 2B (PCV-10)ExperimentalIn Step 2, women who received placebo in step 1 that were randomized to Arm 2B were administered a 0.5 mL dose of PCV-10 intramuscularly once.
Receives: Biological: PCV-10
Step 3 (PCV-10)ExperimentalIn Step 3, women who received placebo in step 1 and failed entry into step 2 due to ongoing new pregnancy were administered a 0.5 mL dose of PCV-10 intramuscularly once.
Receives: Biological: PCV-10

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Women Who Experienced Various Adverse Events (AEs)

    The number of women who experienced grade ≥ 3 adverse events (AEs) in the 4 weeks after vaccination in Step 1 and grade 4 AEs or death up to 24 weeks post-partum. AE grading (Grade 1- mild to Grade 4-life-threatening) was done by DAIDS AE Grading table v2.0 (see References).

    Measured: up to 24 Weeks Post-Delivery for mother participants.

  2. Number of Women Who Experienced Grade ≥ 3 Adverse Events (AEs) in Step 2

    The number of women who enrolled in Step 2, received vaccine and who experience grade ≥ 3 adverse events (AEs) in the 4 weeks after vaccination in Step 2 is presented.

    Measured: up to 4 Weeks after Step 2 vaccination for Mother Participants

  3. Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy

    The number of infants who experience grade ≥ 3 adverse events (AEs), congenital defects, HIV infections or pneumonia, meningitis or IPD after maternal vaccination in Step 1, assessed from birth through 24 weeks of life for infant participants.

    Measured: through 24 weeks of life for infant participants

  4. Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations

    The number of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 to 1 or more serotypes.

    The proportion of participants with >=0.35ug/mL ELISA-measured IgG PNC antibody concentrations at 28 days after immunization in Step 1 to 1 or more serotypes.

    Measured: 28 days after Immunization in Step 1

  5. Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 8 Weeks of Age

    The number of infant participants with ELISA-measured IgG PNC antibody levels ≥ 0.35ug/mL at 8 weeks of age to 1 or more serotypes.

    Measured: 8 Weeks of Life

Secondary outcomes (5)
  1. Ratio of Infant/Mother PNC Antibody Levels

    The ratios of infant/mother PNC antibody levels to study used serotypes.

    Measured: At Delivery for Mother Participants and Birth for Infant Participants

  2. Number of Participants With a >=0.35ug/mL ELISA-measured IgG PNC Antibody Concentrations at Labor/Delivery and 24 Weeks Post-partum

    The number of participants with a >=0.35ug/mL ELISA-measured IgG PNC antibody concentrations at the time points listed for 1 or more serotypes.

    Measured: at Labor and Delivery and 24 Weeks Post-Delivery for Mother Participants

  3. Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PPV-23 Vaccination in Step 1 and Step 2

    The number of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 vs from entry to Step 2 to 28 days after immunization in Step 2 to 1 or more serotypes.

    Measured: 28 days after Immunization in Step 1 and in Step 2

  4. Number of Participants With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations at 28 Days After PCV-10 Vaccination in Step 1 and Step 2

    The proportion of participants with a two-fold or higher increase in ELISA-measured IgG PNC antibody concentrations from baseline to 28 days after immunization in Step 1 vs from entry to Step 2 to 28 days after immunization in Step 2 to 1 or more serotypes.

    Measured: 28 days after Immunization in Step 1 and in Step 2

  5. Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 16 and 24 Weeks of Age

    The number of infant participants with ELISA-measured IgG PNC antibody levels ≥ 0.35ug/mL at 16 and 24 weeks of age to 1 or more serotypes.

    Measured: at weeks 16 and 24 of life

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Mar 2016 (estimated)
  2. Study startMar 2016
  3. Primary completionNov 2018
  4. Study completionMay 2019

Resources

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
347 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02717494
Sponsor's protocol ID
NICHD P1091
Status last verified
Dec 2019
First submitted
18 Mar 2016
Last updated
18 Jan 2020
Data monitoring committee
Yes

Publications

  • Duarte G, Muresan P, Ward S, Laimon L, Pelton SI, Canniff J, Golner A, Bone F, Newton L, Fenton T, Coutinho CM, Joao EC, Santos BR, Pilotto JH, Oliveira RH, Pinto JA, Machado ES, Kreitchman R, Chakhtoura N, Mussi-Pinhata MM, Weinberg A. Immunogenicity of Conjugated and Polysaccharide Pneumococcal Vaccines Administered During Pregnancy or Postpartum to Women With HIV. J Infect Dis. 2022 Mar 15;225(6):1021-1031. doi: 10.1093/infdis/jiab567.

    PubMed 34791324
  • Weinberg A, Muresan P, Laimon L, Pelton SI, Goldblatt D, Canniff J, Zimmer B, Bone F, Newton L, Fenton T, Kiely J, Johnson MJ, Joao EC, Santos BR, Machado ES, Pinto JA, Chakhtoura N, Duarte G, Mussi-Pinhata MM; NICHD P1091 study team. Safety, immunogenicity, and transplacental antibody transport of conjugated and polysaccharide pneumococcal vaccines administered to pregnant women with HIV: a multicentre randomised controlled trial. Lancet HIV. 2021 Jul;8(7):e408-e419. doi: 10.1016/S2352-3018(20)30339-8. Epub 2021 Apr 27.

    PubMed 33915104

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PPV-23, PCV-10 and NaCl in people with PNC Vaccine and HIV-infected Pregnant Women, run by Westat at 8 sites in Brazil.

The full registered description is in the About this study section and the official record.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Women Who Experienced Various Adverse Events (AEs) (time frame: up to 24 Weeks Post-Delivery for mother participants.). The study lists 5 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 NCT02717494, which also lists 2 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 18 Jan 2020.

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