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

NCT02717494 | Completed Phase 2 Results DMC

• 1 other identifier: NICHD P1091
• Study Type: interventional
• Target: 347
• Locations: 1 country
• Sites: 8

Brief 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 (PPV-23) by comparison with placebo.

Conditions

PNC Vaccine; HIV-infected Pregnant Women

Keywords

PPV-23; PCV-10; HIV; Immunization; Pregnancy

Outcome Measures

Primary Outcomes (5)

• 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).

  up to 24 Weeks Post-Delivery for mother participants.

• 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.

  up to 4 Weeks after Step 2 vaccination for Mother Participants

• 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.

  through 24 weeks of life for infant participants

• 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.

  28 days after Immunization in Step 1

• 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.

  8 Weeks of Life

Secondary Outcomes (5)

• Ratio of Infant/Mother PNC Antibody Levels

  At Delivery for Mother Participants and Birth for Infant Participants

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

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

• 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

  28 days after Immunization in Step 1 and in Step 2

• 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

  28 days after Immunization in Step 1 and in Step 2

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

  at weeks 16 and 24 of life

Study Arms (6)

Arm 1A (PPV-23)

EXPERIMENTAL

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

Biological: PPV-23

Arm 1B (PCV-10)

EXPERIMENTAL

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

Biological: PCV-10

Arm 1C (placebo)

PLACEBO COMPARATOR

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

Other: NaCl

Arm 2A (PPV-23)

EXPERIMENTAL

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.

Biological: PPV-23

Arm 2B (PCV-10)

EXPERIMENTAL

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.

Biological: PCV-10

Step 3 (PCV-10)

EXPERIMENTAL

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.

Biological: PCV-10

Interventions

PPV-23 BIOLOGICAL

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

Arm 1A (PPV-23); Arm 2A (PPV-23)

PCV-10 BIOLOGICAL

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

Arm 1B (PCV-10); Arm 2B (PCV-10); Step 3 (PCV-10)

NaCl OTHER

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

Arm 1C (placebo)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant women ≥ 18 years old who provided written informed consent prior to study initiation.
• 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.
• 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.
• 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.
• Receipt of HAART (a regimen of at least three ARV drugs) for ≥ 4 weeks prior to enrollment.
• Documented platelet count of \> 50,000/mm3 and an absolute neutrophil count (ANC) of \> 500/ mm3 ≤ 28 days prior to study entry.
• Women who were willing and able to comply with the study visits.

You may not qualify if:

• Receipt of any PCV or PPV-23 at any time prior to enrollment, documented by medical history or record.
• Receipt of any live licensed vaccine ≤ 4 weeks or inactivated licensed vaccine ≤ 2 weeks prior to study entry.
• 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.
• 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.
• Women who planed to terminate their pregnancy.
• Women who had a prior history of lupus or other autoimmune disorders.
• 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.
• Ongoing neoplastic disease (excluding non-melanoma skin cancer, and human papilloma virus-related cervical dysplasia, cervical intraepithelial neoplasia (CIN) grades 1, 2 or 3).
• 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.
• 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.
• 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.
• Receipt of Interleukin-2 (IL2), interferon (IFN), granulocyte-macrophage colony-stimulating factor (GMCSF) or other immune mediators ≤ 12 weeks before enrollment.
• History of a severe adverse reaction to inactivated polysaccharide or conjugated vaccines.
• 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.
• 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.

Sponsors & Collaborators

• Westat: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (8)

FUNDEP (Belo Horizonte)

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Hospital Geral de Nova Iguaçu Avenida Henrique Duque Estrada Mayer

Nova Iguaçu, Rio de Janeiro, 26030-380, Brazil

Location

Instituto de Puericultura e Pediatria Martagao Gesteria

Rio de Janeiro, Rio de Janeiro, 21 940 590, Brazil

Location

Hospital dos Servidores (Rio de Janeiro)

Saúde, Rio de Janeiro, 20221-161, Brazil

Location

Universidade de Caxias do Sul. Brasil

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

Location

Hospital Santa Casa Porto Alegre Brazil

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Ribeirão Preto Medical School, University of São Paulo, Brazil

Ribeirão Preto, São Paulo, 14049-900, Brazil

Location

Related Publications (2)

• 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.

  PMID: 34791324 DERIVED

• 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.

  PMID: 33915104 DERIVED

Related Links

• NICHD website
• The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Interventions

10-valent pneumococcal conjugate vaccine

Results Point of Contact

• Title: Lauren Laimon, Senior Study Director
• Organization: Westat

LaurenLaimon@westat.com

240-453-2987

Study Officials

• Adriana Weinberg, MD

  University of Colorado, Denver

  STUDY CHAIR

• Marisa Mussi, MD

  University of Sao Paulo Ribeirão Preto School of Medicine

  STUDY CHAIR

• Geraldo Duarte, MD

  University of Sao Paulo Ribeirão Preto School of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: March 23, 2016
• Study Start: March 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: May 1, 2019
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2019-12

Locations

BR (8)