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

NCT ID: NCT02717494

Last Updated: 2020-01-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

347 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2019-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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PNC Vaccine HIV-infected Pregnant Women

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm 1A (PPV-23)

In Step 1, women in Arm 1A were administered a 0.5 milliliter (mL) dose of PPV-23 intramuscularly once.

Group Type EXPERIMENTAL

PPV-23

Intervention Type BIOLOGICAL

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

Arm 1B (PCV-10)

In Step 1, women in Arm 1B were administered a 0.5 mL dose of PCV-10 intramuscularly once.

Group Type EXPERIMENTAL

PCV-10

Intervention Type BIOLOGICAL

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

Arm 1C (placebo)

In Step 1, women in Arm 1C were administered a 0.5 mL dose of 0.9 percent Sodium Chloride (NaCl) intramuscularly once.

Group Type PLACEBO_COMPARATOR

NaCl

Intervention Type OTHER

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

Arm 2A (PPV-23)

In 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.

Group Type EXPERIMENTAL

PPV-23

Intervention Type BIOLOGICAL

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

Arm 2B (PCV-10)

In 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.

Group Type EXPERIMENTAL

PCV-10

Intervention Type BIOLOGICAL

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

Step 3 (PCV-10)

In 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.

Group Type EXPERIMENTAL

PCV-10

Intervention Type BIOLOGICAL

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

Interventions

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PPV-23

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

Intervention Type BIOLOGICAL

PCV-10

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

Intervention Type BIOLOGICAL

NaCl

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

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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.


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


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.

Exclusion Criteria

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.


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.


None.
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Westat

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adriana Weinberg, MD

Role: STUDY_CHAIR

University of Colorado, Denver

Marisa Mussi, MD

Role: STUDY_CHAIR

University of Sao Paulo Ribeirão Preto School of Medicine

Geraldo Duarte, MD

Role: STUDY_CHAIR

University of Sao Paulo Ribeirão Preto School of Medicine

Locations

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FUNDEP (Belo Horizonte)

Belo Horizonte, Minas Gerais, Brazil

Site Status

Hospital Geral de Nova Iguaçu Avenida Henrique Duque Estrada Mayer

Nova Iguaçu, Rio de Janeiro, Brazil

Site Status

Instituto de Puericultura e Pediatria Martagao Gesteria

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

Hospital dos Servidores (Rio de Janeiro)

Saúde, Rio de Janeiro, Brazil

Site Status

Universidade de Caxias do Sul. Brasil

Caxias do Sul, Rio Grande do Sul, Brazil

Site Status

Hospital Santa Casa Porto Alegre Brazil

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Ribeirão Preto Medical School, University of São Paulo, Brazil

Ribeirão Preto, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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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.

Reference Type DERIVED
PMID: 34791324 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33915104 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

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https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables

The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events

https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids

Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Other Identifiers

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NICHD P1091

Identifier Type: -

Identifier Source: org_study_id

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