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Safety and Immunogenicity of a 10 Valent Pneumococcal Conjugate Vaccine (SIILPCV10) in Healthy Adults, Toddlers, Infants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02308540
Recruitment Status : Completed
First Posted : December 4, 2014
Results First Posted : August 2, 2019
Last Update Posted : August 2, 2019
Sponsor:
Information provided by (Responsible Party):
PATH

Brief Summary:

Phase 1/2, Prospective, Single Center, Randomized, ActiveControlled, Double-Blind, Age De-escalation Study to assess the safety and tolerability of SIILPCV10 administered as a single-dose regimen to healthy Gambian pneumococcal conjugate vaccine (PCV)-naïve young adults and PCV-primed toddlers through 4 weeks post vaccination.

Each adult and toddler subject will undergo a total of 4 clinic visits. Each infant subject will undergo a total of 9 scheduled visits. Blood will be collected from all subjects during the screening visit for safety and potential immunological assessments, and 28 days after completion of the vaccination schedule for immunological assessments. For adults, the vaccine was given intramuscularly into the mid-deltoid muscle of nondominant arm using a 24-gauge needle. For toddlers and infants, the vaccine will be given IM into the anterolateral aspect of the left thigh. Blood will be collected from adults and toddlers for safety labs at the Day 7 post-vaccination visit.


Condition or disease Intervention/treatment Phase
Pneumococcal Disease Biological: SIILPCV10 Biological: Pneumovax 23 Biological: Prevenar 13 Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 346 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1/2, Prospective,Randomized, Active-Controlled, Double-Blind, Age De-escalation Study to Evaluate the Safety, Tolerability, Immunogenicity of Serum Institute of India's PCV10 in Healthy Adults, Toddlers, and Infants
Actual Study Start Date : January 12, 2015
Actual Primary Completion Date : April 2016
Actual Study Completion Date : November 3, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Adult SIILPCV10
Single dose of SIILPCV10 on day 0
Biological: SIILPCV10
10-valent Pneumococcal Conjugate Vaccine (SIILPCV10) at a dosage of 2 µg for each serotype polysaccharide, except 4 µg for 6B serotype, conjugated to a carrier protein (CRM197), with adjuvant (aluminum phosphate [alum]) and preservative (thiomersal).

Active Comparator: Adult Pneumovax 23
Single dose of Pneumovax 23 on day 0
Biological: Pneumovax 23
23-valent Pneumococcal Polysaccharide Vaccine (Pneumovax 23; MSD Pharmaceuticals) for the adult cohort.
Other Name: 23-valent Pneumococcal Polysaccharide Vaccine

Experimental: Toddler SIILPCV10
Single dose of SIILPCV10 on day 0
Biological: SIILPCV10
10-valent Pneumococcal Conjugate Vaccine (SIILPCV10) at a dosage of 2 µg for each serotype polysaccharide, except 4 µg for 6B serotype, conjugated to a carrier protein (CRM197), with adjuvant (aluminum phosphate [alum]) and preservative (thiomersal).

Active Comparator: Toddler Prevenar 13
Single dose of Prevenar 13 on day 0
Biological: Prevenar 13
13-valent Pneumococcal Conjugate Vaccine (Prevenar 13; Pfizer-Wyeth) for the toddler and infant cohorts
Other Name: 13-valent Pneumococcal Conjugate Vaccine

Experimental: Infants SIIL PCV10
A three-dose series of SIILPCV10 on day 0, day 28, and day 56
Biological: SIILPCV10
10-valent Pneumococcal Conjugate Vaccine (SIILPCV10) at a dosage of 2 µg for each serotype polysaccharide, except 4 µg for 6B serotype, conjugated to a carrier protein (CRM197), with adjuvant (aluminum phosphate [alum]) and preservative (thiomersal).

Active Comparator: Infants Prevenar 13
A three-dose series of Prevenar 13 on day 0, day 28, and day 56
Biological: Prevenar 13
13-valent Pneumococcal Conjugate Vaccine (Prevenar 13; Pfizer-Wyeth) for the toddler and infant cohorts
Other Name: 13-valent Pneumococcal Conjugate Vaccine

Experimental: Infant Booster Dose SIILPCV 10
One dose of SIILPCV 10 at 9 months of age
Biological: SIILPCV10
10-valent Pneumococcal Conjugate Vaccine (SIILPCV10) at a dosage of 2 µg for each serotype polysaccharide, except 4 µg for 6B serotype, conjugated to a carrier protein (CRM197), with adjuvant (aluminum phosphate [alum]) and preservative (thiomersal).

Active Comparator: Infant Booster Dose Prevenar 13
One dose of SIILPCV 10 at 9 months of age
Biological: Prevenar 13
13-valent Pneumococcal Conjugate Vaccine (Prevenar 13; Pfizer-Wyeth) for the toddler and infant cohorts
Other Name: 13-valent Pneumococcal Conjugate Vaccine




Primary Outcome Measures :
  1. Adult and Toddler Subjects Experiencing Local and Systemic Reactogenicity, by Severity [ Time Frame: 7 days ]

    Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:

    • At 60 (± 15) minutes following primary vaccination
    • Daily by field workers during Days 1 to 6 post vaccination
    • In the clinic on Day 7 (+3) following each vaccination (Visit 2 for adults and toddlers).

  2. Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 1 [ Time Frame: 7 days ]

    Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:

    • At 60 (± 15) minutes following primary vaccination
    • Daily by field workers during Days 1 to 6 post vaccination
    • In the clinic on 7 days (+3) following each vaccination (Visit 2, 4, and 6 for infants).

  3. Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 2 [ Time Frame: 7 days ]

    Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:

    • At 60 (± 15) minutes following primary vaccination
    • Daily by field workers during Days 1 to 6 post vaccination
    • In the clinic on 7 days (+3) following each vaccination (Visit 2, 4, and 6 for infants).

  4. Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 3 [ Time Frame: 7 days ]

    Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:

    • At 60 (± 15) minutes following primary vaccination
    • Daily by field workers during Days 1 to 6 post vaccination
    • In the clinic on 7 days (+3) following each vaccination (Visit 2, 4, and 6 for infants).

  5. Occurrence, Severity and Relatedness of All Adverse Events in Adults and Toddlers [ Time Frame: 28 days ]
    Reported here are only adverse events occurring in 5% or more of subjects; unless specifically stated, AEs were regarded as unrelated.

  6. Occurrence, Severity and Relatedness of All Adverse Events in Infants [ Time Frame: 12 weeks post last vaccination ]
    Reported here are adverse events that occurred in 5% or more of the infant cohort. Booster dose safety results are reported separately. Unless stated, AEs are regarded as unrelated.

  7. Occurrence, Severity and Relatedness of Clinically Significant Hematological and Biochemistry Lab Values in Adults and Toddlers [ Time Frame: 7 days after vaccination ]
    Blood samples were collected for safety hematology and clinical chemistry evaluations, organ function tests, and, for adults, coagulation panel evaluation. Laboratory assessments were only performed at baseline for infants. Testing for HIV was undertaken only following pre-test counseling of the subject/subject's parent as to the implications of the test result. Post test counseling was also undertaken, and on the basis of a positive result the subject and subject's parents would have been referred on for HIV care according to normal local practice in The Gambia.


Secondary Outcome Measures :
  1. Geometric Mean Concentration of Immunoglobulin G (IgG) for Adults [ Time Frame: 4 weeks after vaccination ]
    Serum samples were collected 28 days after the vaccination in adults to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10.

  2. Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Toddlers [ Time Frame: 4 weeks after vaccination ]
    Serum samples were collected 28 days after vaccination for toddlers to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10.

  3. Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Infants [ Time Frame: 4 weeks after the third dose ]
    Serum samples were collected 28 days after the third vaccination for infants to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10.

  4. Geometric Mean Fold Rise (GMFR) of Immunoglobulin G (IgG) in Toddlers, by Serotype [ Time Frame: 4 weeks after vaccination (28 days) ]
    Serum samples were collected before the first vaccination and 28 days after the last vaccination for adults and toddlers and 28 days after the completion of the primary series for infants to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10. Blood samples were also collected for immunogenicity testing before and 28 days after the booster dose for infants. Baseline serum samples for infants and adults were not assayed. The IgG concentration was also determined for each component of the co administered pentavalent vaccine (DTwP-HepB-Hib) in sera from the infant cohort. If there were limitations to blood volumes, appropriate subsets and priorities for immune testing were established with the immunology laboratories to ensure measurements were unbiased and representative of the entire cohort.

  5. Number and Percentage of Immunoglobulin G (IgG) Seroresponders Among Infants, by Serotype [ Time Frame: 4 weeks after third dose ]
    Seroresponse was defined as ≥ 0.35 µg/mL. In infants, serum samples were collected 28 days after receipt of three doses of the vaccine to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10.

  6. Functional Antibody (OPA) Geometric Mean Titers [ Time Frame: 4 weeks after last vaccination ]
    The functional activity of the IgG response to the 10 serotypes contained in SIILPCV10 was determined in randomly selected subsets of the infant and toddler cohorts and all adult subjects in the same serum samples collected 28 days after the last vaccinations. This activity was determined using the 4-fold multiplexed OPA developed at the University of Alabama at Birmingham.

  7. Number and Percentage of Functional (OPA) Infant Seroresponders, by Serotype [ Time Frame: 84 days ]
    The functional activity of the immune response to the 10 serotypes contained in SIILPCV10 was determined in randomly selected subsets of the infant cohort in the same serum samples collected 28 days after the completion of the primary series. This activity was determined using the 4-fold multiplexed OPA developed at the University of Alabama at Birmingham.

  8. Number and Percentage of Immunoglobulin G (IgG) Seroresponders Against Pentavalent Vaccine Components [ Time Frame: 84 days ]

    Serum samples were collected 28 days after the third vaccination for infants to determine the ELISA IgG concentration for each component of the co administered pentavalent vaccine (DTwP-HepB-Hib) . Seroresponse was defined as equal to or greater concentrations for:

    • Diptheria toxoid: 0.1 IU/mL
    • Hepatitis B: 10 milli-International unit (mIU) /mL
    • Hib: 0.15 mcg/mL
    • Tetanus toxoid: 0.1 IU/mL


Other Outcome Measures:
  1. Infant Subjects Experiencing Local and Systemic Reactogenicity After Booster Vaccination, by Severity [ Time Frame: 7 days ]

    Local and systemic reactogenicity of the study vaccine was evaluated for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [potentially life threatening]) and relatedness to the vaccination. Injection site events were by definition considered related to study vaccine. Reactogenicity was monitored at the following times:

    • At 30 (± 10) minutes following booster vaccination
    • Daily by field workers during Days 1 to 6 post vaccination
    • In the clinic on 7 days (+3) following the vaccination

  2. Occurrence of All Adverse Events (AEs) and SAEs Following a Booster Vaccination Among Infants, by Type and Severity [ Time Frame: 4 weeks (28 days) ]
    Unsolicited adverse events following a booster dose of SIILPCV10 occurring in 5% or greater of study participants. Unless specifically stated, AEs are considered unrelated.

  3. Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) by Time Point (4 Weeks Post Vaccination 3, Pre Booster, 4 Weeks Post Booster) Among Infants Receiving Booster Dose [ Time Frame: 4 weeks (28 days) ]
    Using enzyme-linked immunosorbent assay (ELISA). Blood samples were collected for immunogenicity testing at 4 weeks post vaccination 3, and before and 28 days after the booster dose for infants.

  4. Geometric Mean Fold Rise (GMFR) in Immunoglobulin G (IgG) Among Infants Receiving a Booster Dose [ Time Frame: 4 weeks (28 days) ]
    Using enzyme-linked immunosorbent assay (ELISA). Blood samples were collected for immunogenicity testing before and 28 days after the booster dose for infants.

  5. Antibody Persistence of Immunoglobulin G (IgG) Geometric Mean Concentration Among Infants Receiving a Booster Dose [ Time Frame: 20-23 weeks ]
    Defined as the ratio of IgG geometric mean concentration (GMC) measured prior to the infant booster dose, to GMC measured 4 weeks after the 3-dose primary series. Infants received the booster dose at least four weeks after they received routine Expanded Program on Immunization (EPI) vaccines, which occurred at 9 months of age. Thus, the time frame was at least 20 weeks but may have been longer.

  6. Booster Effect: Ratio of Immunoglobulin G (IgG) Geometric Mean Concentration 4 Weeks Post Vaccination 3 Versus 4 Weeks Post Booster Among Infants Receiving a Booster Dose [ Time Frame: 24-26 weeks ]
    Defined as the ratio of IgG geometric mean concentration (GMC) measured 4 weeks post-infant booster dose, to GMC measured 4 weeks after the 3-dose primary series. Infants received the booster dose at least four weeks after they received routine Expanded Program on Immunization (EPI) vaccines, which occurred at 9 months of age. Thus, the time frame was at least 24 weeks but may have been longer.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • • Healthy adults (18-40 yrs), toddlers (12-15 mo), full term infants (6-8 wks) and ≥ 3.5 kg

    • Able to provide informed consent (for themselves or child)
    • Willing to comply with study requirements and procedures.
    • Toddlers have completed their Gambian infant EPI schedule
    • Infants who have received the birth doses of BCG, HepB and OPV but who have not received any additional vaccines.
    • Infants and toddlers with a weight-to-height Z score of ≥ -2.
    • Subjects resident in the study area with no plans to travel outside the study area during the period of study participation.

Exclusion Criteria:

  • Use of any investigational medicinal product within 90 days prior to randomization and throughout the study.
  • Ingestion of herbal or other traditional local medication within 14 days of randomization.
  • Adults and infants who have previously been vaccinated against S. pneumoniae.
  • History of S. pneumoniae infection confirmed by culture from a normally sterile site.
  • History of allergic disease or history of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines.
  • History of anaphylactic shock.
  • Screening laboratory test or vital signs outside the normal range.
  • HIV-positive or HbsAg- positive based on testing during screening.
  • Acute illness (moderate or severe) and/or fever (axillary temperature of ≥ 38.0°C for adults or ≥ 37.5°C for toddlers and infants).
  • Use of antibiotics within 5 days of randomization (excluding treatment for malaria).
  • A positive test for malaria at time of screening, which remains positive post treatment when retested at time of randomization (Day 0).
  • Administration of any non-study vaccine within 30 days prior to administration of study vaccine or planned vaccination during the course of study participation.
  • Chronic administration of immunosuppressant or other immune modifying drugs prior to the administration of the study. The use of topical and inhaled glucocorticoids will be permitted.
  • Administration of immunoglobulins and/or any blood products within the 6 months prior to administration of the study vaccine or during the study period.
  • History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding.
  • Employee of, or direct descendant of any person employed by the Sponsor, the CRO, the PI, study site personnel, or site.

Adults only

  • Recent history or signs of alcohol or substance abuse.
  • History of major psychiatric disorder.
  • Female adult subjects who are pregnant or breast-feeding. Infants/Toddlers only
  • Family history of suspected primary immunodeficiency in first-degree relative.
  • Had a sibling die suddenly and without apparent other cause or preceding illness in the first year of life.
  • Evidence of a clinically significant congenital abnormality as judged by the PI.
  • Evidence of fetal alcohol syndrome or maternal history of alcohol abuse during pregnancy.
  • History of meningitis, seizures or any neurological disorder.
  • Evidence of exposure to an HIV-positive individual through maternal fetal transmission, breast milk, or other bloodborne mechanisms

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02308540


Locations
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Gambia
Medical Research Council (MRC) Unit, The Gambia
Fajara, Gambia
Sponsors and Collaborators
PATH
Investigators
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Principal Investigator: Ed Clarke, MD PhD Medical Research Council (MRC) Unit, The Gambia

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Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT02308540     History of Changes
Other Study ID Numbers: VAC-017
First Posted: December 4, 2014    Key Record Dates
Results First Posted: August 2, 2019
Last Update Posted: August 2, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Pneumococcal Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs