Safety & Immunogenicity of 13vPnC in HIV-Infected Subjects Aged 18 or Older Who Were Previously Immunized With 23vPS

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00963235
First received: August 20, 2009
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

The study will evaluate the safety, tolerability and immunogenicity of a 13-valent pneumococcal conjugate vaccine (13vPnC) in HIV-infected subjects 18 years of age or older who have been previously immunized with at least one dose of 23-valent pneumococcal polysaccharide vaccine (23vPS). All subjects will receive 3 doses of 13vPnC, with each study vaccine dose given approximately 6 months apart.


Condition Intervention Phase
HIV Infections
Pneumococcal Infections
Biological: 13-valent pneumococcal conjugate vaccine
Procedure: Blood draw
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase 3, Open-label, Single-Arm Trial to Evaluate the Safety, Tolerability, and Immunogenicity of 3 Doses of 13vPnC Vaccine in HIV-Infected Subjects 18 Years of Age or Older Who Have Been Previously Immunized With 23vPS Vaccine

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After Dose 2 of 13vPnC to 1 Month After Dose 3 of 13vPnC [ Time Frame: 1 month post-dose 2, 1 month post-dose 3 ] [ Designated as safety issue: No ]
    Geometric mean fold rises (GMFRs) for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month post-dose 2 to 1 month post-dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for the GMFRs were back transformations of a CI based on the Student t distribution for the logarithmically transformed assay results.


Secondary Outcome Measures:
  • Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After Dose 3 of 13vPnC Relative to 1 Month After Dose 2 of 13vPnC [ Time Frame: 1 month post-dose 2, 1 month post-dose 3 ] [ Designated as safety issue: No ]
    Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means (GMs) were calculated using all participants with available data for both post-dose 2 and post-dose 3 blood draws.

  • Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After Dose 2 of 13vPnC Relative to 1 Month After Dose 1 of 13vPnC [ Time Frame: 1 month post-dose 1, 1 month post-dose 2 ] [ Designated as safety issue: No ]
    Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were presented. GMC (13vPnC) and corresponding 2-sided 95% CI were evaluated. GMs were calculated using all participants with available data for both post-dose 1 and post-dose 2 blood draws.

  • Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) 1 Month After Dose 3 of 13vPnC Relative to 1 Month After Dose 2 of 13vPnC [ Time Frame: 1 month post-dose 2, 1 month post-dose 3 ] [ Designated as safety issue: No ]
    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 all the participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CI were evaluated. GMs were calculated using all participants with available data for both post-dose 2 and post-dose 3 blood draws.

  • Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) 1 Month After Dose 2 of 13vPnC Relative to 1 Month After Dose 1 of 13vPnC [ Time Frame: 1 month post-dose 1, 1 month post-dose 2 ] [ Designated as safety issue: No ]
    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 all the participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CI were evaluated. GMs were calculated using all participants with available data for both post-dose 2 and post-dose 3 blood draws.

  • Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rise (GMFR) From 1 Month After Dose 2 of 13vPnC to 1 Month After Dose 3 of 13vPnC [ Time Frame: 1 month post-dose 2, 1 month post-dose 3 ] [ Designated as safety issue: No ]
    GMFRs for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month post-dose 2 to 1 month post-dose 3 were computed using the logarithmically transformed assay results. CI for the GMFRs were back transformations of a CI based on the Student t distribution for the logarithmically transformed assay results.

  • Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rise (GMFR) From 1 Month After Dose 1 of 13vPnC to 1 Month After Dose 2 of 13vPnC [ Time Frame: 1 month post-dose 1, 1 month post-dose 2 ] [ Designated as safety issue: No ]
    GMFRs for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month post-dose 1 to 1 month post-dose 2 were computed using the logarithmically transformed assay results. CI for the GMFRs were back transformations of a CI based on the Student t distribution for the logarithmically transformed assay results.


Other Outcome Measures:
  • Percentage of Participants Reporting Pre-Specified Local Reactions: 13vPnC Dose 1 [ Time Frame: Within 14 days post-dose 1 ] [ Designated as safety issue: Yes ]
    Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling scaled as Any (redness present or swelling present); Mild (2.5 to 5.0 centimeters [cm]); Moderate (5.5 to 10.0 cm); Severe (greater than [>] 10 cm). Pain scaled as Any (pain present); Mild (awareness of pain; easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating).

  • Percentage of Participants Reporting Pre-Specified Local Reactions: 13vPnC Dose 2 [ Time Frame: Within 14 days post-dose 2 ] [ Designated as safety issue: Yes ]
    Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling scaled as Any (redness present or swelling present); Mild (2.5 to 5.0 cm); Moderate (5.5 to 10.0 cm); Severe (>10 cm). Pain scaled as Any (pain present); Mild (awareness of pain; easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating).

  • Percentage of Participants Reporting Pre-Specified Local Reactions: 13vPnC Dose 3 [ Time Frame: Within 14 days post-dose 3 ] [ Designated as safety issue: Yes ]
    Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling scaled as Any (redness present or swelling present); Mild (2.5 to 5.0 cm); Moderate (5.5 to 10.0 cm); Severe (>10 cm). Pain scaled as Any (pain present); Mild (awareness of pain; easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating).

  • Percentage of Participants Reporting Pre-Specified Systemic Events: 13vPnC Dose 1 [ Time Frame: Within 14 days post-dose 1 ] [ Designated as safety issue: Yes ]
    Specific systemic events (fever greater than or equal to [>=]38 degrees Celsius[C], fatigue, headache, vomiting, diarrhea, new generalized muscle/joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, new generalized muscle and joint pain were scaled as: Any (symptom present); Mild (no interference with activity); Moderate (some interference); Severe (prevents routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hours [hrs]); Moderate (>2 times in 24 hrs); Severe (requires intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hrs); Moderate (4-5 loose stools 24 hrs); Severe (>=6 loose stools in 24 hrs). Report of fever >40 degrees C after 13vPnC Dose 1 was confirmed as data entry error.

  • Percentage of Participants Reporting Pre-Specified Systemic Events: 13vPnC Dose 2 [ Time Frame: Within 14 days post-dose 2 ] [ Designated as safety issue: Yes ]
    Specific systemic events (fever >=38 degrees C, fatigue, headache, vomiting, diarrhea, new generalized muscle/joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, new generalized muscle and joint pain were scaled as: Any (symptom present); Mild (no interference with activity); Moderate (some interference); Severe (prevents routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hrs); Moderate (>2 times in 24 hrs); Severe (requires intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hrs); Moderate (4-5 loose stools 24 hrs); Severe (>=6 loose stools in 24 hrs).

  • Percentage of Participants Reporting Pre-Specified Systemic Events: 13vPnC Dose 3 [ Time Frame: Within 14 days post-dose 3 ] [ Designated as safety issue: Yes ]
    Specific systemic events (fever >=38 degrees C, fatigue, headache, vomiting, diarrhea, new generalized muscle/joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, new generalized muscle and joint pain were scaled as: Any (symptom present); Mild (no interference with activity); Moderate (some interference); Severe (prevents routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hrs); Moderate (>2 times in 24 hrs); Severe (requires intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hrs); Moderate (4-5 loose stools 24 hrs); Severe (>=6 loose stools in 24 hrs).


Enrollment: 331
Study Start Date: November 2009
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Biological: 13-valent pneumococcal conjugate vaccine
Three doses of 13vPnC given 6 months apart.
Other Name: 13vPnC
Procedure: Blood draw
Six blood draws pre-vaccination and 1 month post-vaccination, doses 1-3.
Other Name: Blood draw

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects aged 18 years or older at the time of enrollment.
  • All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control from the signing of the informed consent form (ICF) until 3 months after the last dose of investigational product.
  • Documented vaccination with 1 or more doses of 23vPS at least 6 months before study enrollment.
  • CD4+ T-cell count >= 200 cells/µ, obtained on the most recent 2 occasions within 6 months before the first investigational product vaccination.
  • HIV-infected subjects with viral load <50,000 copies/mL, obtained on the most recent 2 occasions within 6 months before the first investigational product vaccination.
  • Subject is receiving a stable dose of HAART for at least 6 weeks prior to the first investigational product vaccination, or not currently receiving antiretroviral therapy.
  • Subject is expected to be available for the entire study period (approximately 18 months) and can be contacted by telephone.
  • Subject must be able to complete an electronic diary (e-diary) and complete all relevant study procedures during study participation.
  • Subject is deemed to be eligible for the study on the basis of medical history, physical examination, and clinical judgment. (Note: Subjects with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease 6 weeks before investigational product vaccination, are eligible.)

Exclusion Criteria:

  • Subjects with active AIDS related illness, including opportunistic infections or malignancy.
  • Evidence of current illicit substance and/or alcohol abuse, that in the investigator's opinion, precludes the subject from participating in the study or interferes with the evaluation of the study objectives..
  • Receipt of any licensed or experimental pneumococcal conjugate vaccine prior to enrollment.
  • Contraindication to vaccination with pneumococcal conjugate vaccine.
  • Previous anaphylactic reaction to any vaccine or vaccine-related component.
  • History of culture-proven invasive disease caused by Streptococcus pneumoniae within the last year.
  • Current anticoagulant therapy or a history of bleeding diathesis or any condition associated with prolonged bleeding time that would contraindicate intramuscular injection. (Note: Use of antiplatelet drugs, such as aspirin and clopidogrel, is permitted.)
  • Pregnant or breastfeeding women, as defined by history or positive human chorionic gonadotropin (hCG) urine test. All women of childbearing potential must have a urine pregnancy test.
  • History of active hepatitis with elevation in pretreatment aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >5 times the upper limit of normal within the last 6 months.
  • Serious chronic disorder or any other disorder that, in the investigator's opinion, precludes the subject from participating in the study or interferes with the evaluation of the study objectives. (Note: Serious chronic disorders include metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end-stage renal disease with or without dialysis, and clinically unstable cardiac disease).
  • Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of, the study, or could preclude the evaluation of the subject's response.
  • History of splenectomy.
  • Receipt of any blood products, including immunoglobulin, within 42 days before investigational product vaccination until the last blood draw for the study (approximately 13 months after the first investigational product vaccination).
  • Evidence of dementia or other severe cognitive impairment.
  • Subject who is, in the opinion of the investigator, unable to receive a vaccination in the deltoid muscle of either arm because of insufficient muscle mass.
  • Participation in another study using investigational product from 28 days before study enrollment until the blood draw at visit 6. Between the blood draw at visit 6 and the 6 month follow-up telephone call (visit 7), use of investigational product must be discussed with the Medical Monitor. (Note: Participation in purely observational studies is acceptable.)
  • Residence in a nursing home, long-term care facility, or other institution or requirement of semi-skilled nursing care. An ambulatory resident of a retirement home or village is eligible for the trial.
  • Subject who is a direct relative (child, grandchild, parent, or grandparent) of study personnel, or who is study personnel.

Temporary Delay Criteria:

  • Current febrile illness (oral temperature of =38.0°C [100.4°F]) or other acute illness within 48 hours before study vaccine administration.
  • Currently receiving antibiotic therapy, or has completed a course of antibiotic therapy within 10 days before study vaccine administration.
  • Receipt of novel influenza A (H1N1) vaccine within 14 days before investigational product vaccination (seasonal influenza vaccine can be given at any time at the discretion of the investigator).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00963235

Locations
United States, California
Pfizer Investigational Site
San Francisco, California, United States, 94115
United States, Colorado
Pfizer Investigational Site
Aurora, Colorado, United States, 80045
United States, District of Columbia
Pfizer Investigational Site
Washington, District of Columbia, United States, 20009
United States, Kentucky
Pfizer Investigational Site
Lexington, Kentucky, United States, 40536
United States, Massachusetts
Pfizer Investigational Site
Springfield, Massachusetts, United States, 01199
United States, Missouri
Pfizer Investigational Site
St. Louis, Missouri, United States, 63110
United States, New York
Pfizer Investigational Site
New York, New York, United States, 10016
Pfizer Investigational Site
New York, New York, United States, 10029
Pfizer Investigational Site
New York, New York, United States, 10032
Pfizer Investigational Site
New York, New York, United States, 10011
Pfizer Investigational Site
New York, New York, United States, 10065
Pfizer Investigational Site
Rochester, New York, United States, 14642
United States, Tennessee
Pfizer Investigational Site
Johnson City, Tennessee, United States, 37604
United States, Texas
Pfizer Investigational Site
Austin, Texas, United States, 78705
Pfizer Investigational Site
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00963235     History of Changes
Other Study ID Numbers: 6115A1-3017, B1851028
Study First Received: August 20, 2009
Results First Received: April 17, 2013
Last Updated: April 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
vaccine
13-valent pneumococcal conjugate vaccine
human immunodeficiency virus

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumococcal Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on October 16, 2014