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

Phase 2

Completed

• Conditions: HIV-infected Pregnant Women; PNC Vaccine
• Interventions: Other: NaCl; Biological: PCV-10; Biological: PPV-23

• Registration Number: NCT02717494
• Lead Sponsor: Westat

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.

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.

Study Timeline

• Study Start: 2016-03
• Study First Submitted: 2016-03-18
• Study First Submitted QC: 2016-03-22
• Study First Posted: 2016-03-23
• Primary Completion: 2018-11
• Study Completion: 2019-05
• Results First Submitted: 2019-11-06
• Status Verified: 2019-12
• Results First Submitted QC: 2019-12-31
• Last Update Submitted: 2019-12-31
• Results First Posted: 2020-01-18
• Last Update Posted: 2020-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 347

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1C (placebo)	NaCl	In Step 1, women in Arm 1C were administered a 0.5 mL dose of 0.9 percent Sodium Chloride (NaCl) intramuscularly once.
Arm 1B (PCV-10)	PCV-10	In Step 1, women in Arm 1B were administered a 0.5 mL dose of PCV-10 intramuscularly once.
Arm 2A (PPV-23)	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.
Arm 1A (PPV-23)	PPV-23	In Step 1, women in Arm 1A were administered a 0.5 milliliter (mL) dose of PPV-23 intramuscularly once.
Step 3 (PCV-10)	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.
Arm 2B (PCV-10)	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.

Primary Outcome Measures

Name	Time	Method
Number of Women Who Experienced Various Adverse Events (AEs)	up to 24 Weeks Post-Delivery for mother participants.	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).
Number of Women Who Experienced Grade ≥ 3 Adverse Events (AEs) in Step 2	up to 4 Weeks after Step 2 vaccination for Mother Participants	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.
Number of Women With a Two-fold or Higher Increase in ELISA-measured IgG PNC Antibody Concentrations	28 days after Immunization in Step 1	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.
Number of Infants With Various Adverse Events Following Maternal Vaccination With PCV10 and PPV23 Administered in Pregnancy	through 24 weeks of life for infant participants	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.
Number of Infant Participants With ELISA-measured IgG PNC Antibody Levels ≥ 0.35ug/mL at 8 Weeks of Age	8 Weeks of Life	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.

Secondary Outcome Measures

Name	Time	Method
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	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.
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	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.
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	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.
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	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.
Ratio of Infant/Mother PNC Antibody Levels	At Delivery for Mother Participants and Birth for Infant Participants	The ratios of infant/mother PNC antibody levels to study used serotypes.

Trial Locations

Locations (8)

FUNDEP (Belo Horizonte); 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Hospital dos Servidores (Rio de Janeiro); 🇧🇷 Saude, Rio De Janeiro, Brazil

Hospital Geral de Nova Iguaçu Avenida Henrique Duque Estrada Mayer; 🇧🇷 Nova Iguaçu, Rio De Janeiro, Brazil

Universidade de Caxias do Sul. Brasil; 🇧🇷 Caxias do Sul, RS, Brazil

Instituto de Puericultura e Pediatria Martagao Gesteria; 🇧🇷 Rio de Janeiro, RJ, Brazil

Hospital Santa Casa Porto Alegre Brazil; 🇧🇷 Porto Alegre, RS, Brazil

Ribeirão Preto Medical School, University of São Paulo, Brazil; 🇧🇷 Ribeirao Preto, Sao Paulo, Brazil

Hospital Nossa Senhora da Conceicao; 🇧🇷 Porto Alegre, RS, Brazil