Safety and Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) in HIV-Infected Subjects 6 Years of Age or Older Who Are Naive to Pneumococcal Vaccine

A Phase 3, Open-label, Single-Arm Trial to Evaluate the Safety, Tolerability and Immunogenicity of 2 and 3 Doses of 13vPnC in HIV-Infected Subjects 6 Years of Age and Older Who Have Not Been Previously Immunized With Pneumococcal Vaccine

The study will evaluate the safety, tolerability and immunogenicity of a 13-valent pneumococcal conjugate vaccine (13vPnC) in HIV-infected subjects 6 years of age or older who have not been previously immunized with a pneumococcal vaccine. All subjects will receive 3 doses of 13vPnC and 1 dose of 23-valent pneumococcal polysaccharide vaccine (23vPS), with each dose given approximately 1 month apart.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Pneumococcal Infections
• Intervention / Treatment: Biological: 13-valent Pneumococcal Conjugate Vaccine (13vPnC); Biological: 23-valent Pneumococcal Polysaccharide Vaccine (23vPS); Procedure: Blood draw; Procedure: Blood draw

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 3

Contacts and Locations

Study Locations

• Romania
  • Bucuresti, Romania, 021105
    • Pfizer Investigational Site
  • Bucuresti, Romania, 030303
    • Pfizer Investigational Site
  • Constanta, Romania, 900709
    • Pfizer Investigational Site
• South Africa
  • Bloemfontein, South Africa, 9301
    • Pfizer Investigational Site
  • Paarl, South Africa, 7626
    • Pfizer Investigational Site
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2013
      • Pfizer Investigational Site
    • Pretoria, Gauteng, South Africa, 0083
      • Pfizer Investigational Site
    • Pretoria, Gauteng, South Africa, 0122
      • Pfizer Investigational Site
    • Soweto, Gauteng, South Africa, 1818
      • Pfizer Investigational Site
  • KwaZulu-Natal
    • Dundee, KwaZulu-Natal, South Africa, 3000
      • Pfizer Investigational Site
  • Western Cape
    • Worcester, Western Cape, South Africa, 6850
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Human immunodeficiency virus (HIV)-infected subjects aged 6 years or older
• Viral load < 50,000 copies/mL and CD4+ T cell count >= 200/uL within 6 months before study vaccination
• Receiving stable highly active antiretroviral therapy (HAART) or not currently receiving any antiretroviral therapy
• No previous vaccination with a pneumococcal vaccine
• Subject or parent/legal guardian able to complete an electronic diary

Exclusion Criteria:

• Acquired immune deficiency syndrome (AIDS) at time of enrollment
• Current illicit substance and/or alcohol abuse
• History of active chronic viral hepatitis
• Previous anaphylactic reaction to a vaccine or vaccine-related component
• Serious chronic disorders including metastatic malignancy and end-stage renal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; 3 doses of 13vPnC and 1 dose of 23vPS, each dose given approximately 1 month apart

Biological: 13-valent Pneumococcal Conjugate Vaccine (13vPnC); 13vPnC; 3 vaccinations given at approximately 1 month intervals at visits 1-3; Biological: 23-valent Pneumococcal Polysaccharide Vaccine (23vPS); 23vPS; 1 vaccination given at visit 4 (approximately 1 month after visit 3); Procedure: Blood draw; Blood draw; 5 blood draws approximately 1 month apart taken prior to vaccination at visits 1-4 and visit 5 (approximately 1 month after visit 4).; Procedure: Blood draw; 1 or 2 blood draws for CD4+ T cell count and HIV viral load at least 6 weeks apart, if subject does not have 2 CD4+ T cell counts and HIV viral load counts within 6 months before visit 1.; Other Names: Screening blood draw(s)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After 13vPnC Dose 2 to 1 Month After 13vPnC Dose 3 in All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 2 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws.	1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose 3 Relative to 1 Month After 13vPnC Dose 2 in Pediatric, Adult and All Participants	Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for pediatric, adult and all participants are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.	1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3
Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Month After 13vPnC Dose 3 Relative to 1 Month After 13vPnC Dose 2 in Pediatric, Adult and All Participants	Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of pediatric, adult and all participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws. CI for GMT were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.	1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3
Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) From 1 Month After 13vPnC Dose 2 to 1 Month After 13vPnC Dose 3 in Pediatric, Adult and All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 2 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws.	1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3
Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After 13vPnC Dose 2 to 1 Month After 13vPnC Dose 3 in Pediatric and Adult Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 2 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 2 and after 13vPnC Dose 3 blood draws.	1 month after 13vPnC Dose 2, 1 month after 13vPnC Dose 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Before and 1 Month After 13vPnC Dose 1 in Pediatric, Adult and All Participants	Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for pediatric, adult and all participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for both the before and after 13vPnC Dose 1 blood draws. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.	Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1
Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 1 in Pediatric, Adult and All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 1 to 1 month after 13vPnC Dose 1 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both before 13vPnC Dose and after 13vPnC Dose 1 blood draws.	Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1
Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) Before and 1 Month After 13vPnC Dose 1 in Pediatric, Adult and All Participants	Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of pediatric, adult and all participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for both the before and after 13vPnC Dose 1 blood draws. CI for GMT were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.	Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1
Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 1 in Pediatric, Adult and All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 1 to 1 month after 13vPnC Dose 1 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both before 13vPnC Dose and after 13vPnC Dose 1 blood draws.	Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1
Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose 3 and 1 Month After 23vPS Dose in Pediatric, Adult and All Participants	Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for pediatric, adult and all participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for both after 13vPnC Dose 3 and after 23vPS Dose blood draws. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.	1 month after 13vPnC Dose 3, 1 month after 23vPS Dose
Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After 13vPnC Dose 3 to 1 Month After 23vPS Dose in Pediatric, Adult and All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 3 to 1 month after 23vPS Dose were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 3 and 1 month after 23vPS Dose blood draws.	1 month after 13vPnC Dose 3, 1 month after 23vPS Dose
Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Month After 13vPnC Dose 3 and 1 Month After 23vPS Dose in Pediatric, Adult and All Participants	Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of pediatric, adult and all participants using a mcOPA assay. GMT (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for both after 13vPnC Dose 3 and after 23vPS Dose blood draws. CI for GMT were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.	1 month after 13vPnC Dose 3, 1 month after 23vPS Dose
Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rise (GMFR) From 1 Month After 13vPnC Dose 3 to 1 Month After 23vPS Dose in Pediatric, Adult and All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 3 to 1 month after 23vPS Dose were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 3 and 1 month after 23vPS Dose blood draws.	1 month after 13vPnC Dose 3, 1 month after 23vPS Dose
Percentage of Pediatric, Adult and All Participants Reporting Pre-Specified Local Reactions: 13vPnC Dose 1	Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling were scaled as Any (redness present or swelling present); Mild (0.5 to 2.0 centimeters (cm) for participants aged 6 to <12 years and 2.5 to 5.0 cm for participants aged greater than (>) 12 years); Moderate (2.5 to 7.0 cm for participants aged 6 to <12 years and 5.1 to 10.0 cm for participants aged >12 years); Severe (>7 cm for participants aged 6 to <12 years and >10 cm for participants aged >12 years). Pain at injection site was scaled as Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity). Report of severe swelling was confirmed as data entry error.	Within 14 days after 13vPnC Dose 1
Percentage of Pediatric, Adult and All Participants Reporting Pre-Specified Local Reactions: 13vPnC Dose 2	Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling were scaled as Any (redness present or swelling present); Mild (0.5 to 2.0 cm for participants aged 6 to <12 years and 2.5 to 5.0 cm for participants aged >12 years); Moderate (2.5 to 7.0 cm for participants aged 6 to <12 years and 5.1 to 10.0 cm for participants aged >12 years); Severe (>7 cm for participants aged 6 to <12 years and >10 cm for participants aged >12 years). Pain at injection site was scaled as Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity).	Within 14 days after 13vPnC Dose 2
Percentage of Pediatric, Adult and All Participants Reporting Pre-Specified Local Reactions: 13vPnC Dose 3	Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling were scaled as Any (redness present or swelling present); Mild (0.5 to 2.0 cm for participants aged 6 to <12 years and 2.5 to 5.0 cm for participants aged >12 years); Moderate (2.5 to 7.0 cm for participants aged 6 to <12 years and 5.1 to 10.0 cm for participants aged >12 years); Severe (>7 cm for participants aged 6 to <12 years and >10 cm for participants aged >12 years). Pain at injection site was scaled as Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity).	Within 14 days after 13vPnC Dose 3
Percentage of Pediatric, Adult and All Participants Reporting Pre-Specified Systemic Events: 13vPnC Dose 1	Specific systemic events (fever >=38 degrees Celsius[C], fatigue, headache, vomiting, diarrhea, muscle pain, joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any (symptom present); Mild (did not interfere with activity); Moderate (some interference with activity); Severe (prevented routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hours); Moderate (>2 times in 24 hours); Severe (required intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hours); Moderate (4-5 loose stools 24 hours); Severe (>=6 loose stools in 24 hours). All reporting of fever >40 degrees C except 2 participants and all reporting of severe vomiting, after 13vPnC Dose 1, were confirmed as data entry errors.	Within 14 days after 13vPnC Dose 1
Percentage of Pediatric, Adult and All Participants Reporting Pre-Specified Systemic Events: 13vPnC Dose 2	Specific systemic events (fever >=38 degrees Celsius[C], fatigue, headache, vomiting, diarrhea, muscle pain, joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any (symptom present); Mild (did not interfere with activity); Moderate (some interference with activity); Severe (prevented routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hours); Moderate (>2 times in 24 hours); Severe (required intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hours); Moderate (4-5 loose stools 24 hours); Severe (>=6 loose stools in 24 hours). All reporting of fever >40 degrees C and all reporting of severe vomiting, after 13vPnC Dose 2, were confirmed as data entry errors.	Within 14 days after 13vPnC Dose 2
Percentage of Pediatric, Adult and All Participants Reporting Pre-Specified Systemic Events: 13vPnC Dose 3	Specific systemic events (fever >=38 degrees Celsius[C], fatigue, headache, vomiting, diarrhea, muscle pain, joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any (symptom present); Mild (did not interfere with activity); Moderate (some interference with activity); Severe (prevented routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hours); Moderate (>2 times in 24 hours); Severe (required intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hours); Moderate (4-5 loose stools 24 hours); Severe (>=6 loose stools in 24 hours). All reporting of fever >40 degrees C except 1 participant and all reporting of severe vomiting, after 13vPnC Dose 3, were confirmed as data entry errors.	Within 14 days after 13vPnC Dose 3

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Bhorat AE, Madhi SA, Laudat F, Sundaraiyer V, Gurtman A, Jansen KU, Scott DA, Emini EA, Gruber WC, Schmoele-Thoma B. Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in HIV-infected individuals naive to pneumococcal vaccination. AIDS. 2015 Jul 17;29(11):1345-54. doi: 10.1097/QAD.0000000000000689.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: August 18, 2009
• First Submitted That Met QC Criteria: August 19, 2009
• First Posted (Estimate): August 20, 2009

Study Record Updates

• Last Update Posted (Estimate): November 17, 2014
• Last Update Submitted That Met QC Criteria: November 13, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: vaccine; human immunodeficiency virus; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 6115A1-3002; B1851021