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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00962780
• Other study ID #: 6115A1-3002
• Secondary ID: B1851021
• Status: Completed
• Phase: Phase 3
• First received: August 18, 2009
• Last updated: November 13, 2014
• Start date: March 2010
• Est. completion date: April 2013

Study information

• Verified date: November 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Other known NCT identifiers

• NCT01098370

Recruitment information / eligibility

• Status: Completed
• Enrollment: 303
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections
• Infection
• Pneumococcal Infections

Intervention

Biological:
• 13-valent Pneumococcal Conjugate Vaccine (13vPnC)
13vPnC; 3 vaccinations given at approximately 1 month intervals at visits 1-3
• 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).
• 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.

Locations

Country	Name	City	State
Romania	Pfizer Investigational Site	Bucuresti
Romania	Pfizer Investigational Site	Bucuresti
Romania	Pfizer Investigational Site	Constanta
South Africa	Pfizer Investigational Site	Bloemfontein
South Africa	Pfizer Investigational Site	Dundee	KwaZulu-Natal
South Africa	Pfizer Investigational Site	Johannesburg	Gauteng
South Africa	Pfizer Investigational Site	Paarl
South Africa	Pfizer Investigational Site	Pretoria	Gauteng
South Africa	Pfizer Investigational Site	Pretoria	Gauteng
South Africa	Pfizer Investigational Site	Soweto	Gauteng
South Africa	Pfizer Investigational Site	Worcester	Western Cape

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Romania,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	Yes
Other	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	Yes
Other	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	Yes
Other	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	Yes
Other	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	Yes
Other	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	Yes
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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