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

NCT02308540 | Completed Phase 1 Results DMC

• 1 other identifier: VAC-017
• Study Type: interventional
• Target: 346
• Locations: 1 country
• Sites: 1

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.

Conditions

Pneumococcal Disease

Outcome Measures

Primary Outcomes (7)

• Adult and Toddler Subjects Experiencing Local and Systemic Reactogenicity, by Severity

  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).

  7 days

• Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 1

  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).

  7 days

• Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 2

  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).

  7 days

• Infant Subjects Experiencing Local and Systemic Reactogenicity, by Severity: Vaccination 3

  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).

  7 days

• Occurrence, Severity and Relatedness of All Adverse Events in Adults and Toddlers

  Reported here are only adverse events occurring in 5% or more of subjects; unless specifically stated, AEs were regarded as unrelated.

  28 days

• Occurrence, Severity and Relatedness of All Adverse Events in Infants

  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.

  12 weeks post last vaccination

• Occurrence, Severity and Relatedness of Clinically Significant Hematological and Biochemistry Lab Values in Adults and Toddlers

  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.

  7 days after vaccination

Secondary Outcomes (8)

• Geometric Mean Concentration of Immunoglobulin G (IgG) for Adults

  4 weeks after vaccination

• Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Toddlers

  4 weeks after vaccination

• Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Infants

  4 weeks after the third dose

• Geometric Mean Fold Rise (GMFR) of Immunoglobulin G (IgG) in Toddlers, by Serotype

  4 weeks after vaccination (28 days)

• Number and Percentage of Immunoglobulin G (IgG) Seroresponders Among Infants, by Serotype

  4 weeks after third dose

Other Outcomes (6)

• Infant Subjects Experiencing Local and Systemic Reactogenicity After Booster Vaccination, by Severity

  7 days

• Occurrence of All Adverse Events (AEs) and SAEs Following a Booster Vaccination Among Infants, by Type and Severity

  4 weeks (28 days)

• 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

  4 weeks (28 days)

Study Arms (8)

Adult SIILPCV10

EXPERIMENTAL

Single dose of SIILPCV10 on day 0

Biological: SIILPCV10

Adult Pneumovax 23

ACTIVE COMPARATOR

Single dose of Pneumovax 23 on day 0

Biological: Pneumovax 23

Toddler SIILPCV10

EXPERIMENTAL

Single dose of SIILPCV10 on day 0

Biological: SIILPCV10

Toddler Prevenar 13

ACTIVE COMPARATOR

Single dose of Prevenar 13 on day 0

Biological: Prevenar 13

Infants SIIL PCV10

EXPERIMENTAL

A three-dose series of SIILPCV10 on day 0, day 28, and day 56

Biological: SIILPCV10

Infants Prevenar 13

ACTIVE COMPARATOR

A three-dose series of Prevenar 13 on day 0, day 28, and day 56

Biological: Prevenar 13

Infant Booster Dose SIILPCV 10

EXPERIMENTAL

One dose of SIILPCV 10 at 9 months of age

Biological: SIILPCV10

Infant Booster Dose Prevenar 13

ACTIVE COMPARATOR

One dose of SIILPCV 10 at 9 months of age

Biological: Prevenar 13

Interventions

SIILPCV10 BIOLOGICAL

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).

Adult SIILPCV10; Infant Booster Dose SIILPCV 10; Infants SIIL PCV10; Toddler SIILPCV10

Pneumovax 23 BIOLOGICAL

23-valent Pneumococcal Polysaccharide Vaccine (Pneumovax 23; MSD Pharmaceuticals) for the adult cohort.

Also known as: 23-valent Pneumococcal Polysaccharide Vaccine

Adult Pneumovax 23

Prevenar 13 BIOLOGICAL

13-valent Pneumococcal Conjugate Vaccine (Prevenar 13; Pfizer-Wyeth) for the toddler and infant cohorts

Also known as: 13-valent Pneumococcal Conjugate Vaccine

Infant Booster Dose Prevenar 13; Infants Prevenar 13; Toddler Prevenar 13

Eligibility Criteria

• Age: 4 Weeks - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

Medical Research Council (MRC) Unit, The Gambia

Fajara, The Gambia

Location

Related Publications (1)

• Clarke E, Bashorun AO, Okoye M, Umesi A, Badjie Hydara M, Adigweme I, Dhere R, Sethna V, Kampmann B, Goldblatt D, Tate A, Weiner DH, Flores J, Alderson MR, Lamola S. Safety and immunogenicity of a novel 10-valent pneumococcal conjugate vaccine candidate in adults, toddlers, and infants in The Gambia-Results of a phase 1/2 randomized, double-blinded, controlled trial. Vaccine. 2020 Jan 10;38(2):399-410. doi: 10.1016/j.vaccine.2019.08.072. Epub 2019 Dec 14.

  PMID: 31843266 DERIVED

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

23-valent pneumococcal capsular polysaccharide vaccine; 13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Dr. Steve Lamola
• Organization: PATH

slamola@path.org

1-206-285-3500

Study Officials

• Ed Clarke, MD PhD

  Medical Research Council (MRC) Unit, The Gambia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2014
• First Posted: December 4, 2014
• Study Start: January 12, 2015
• Primary Completion: April 1, 2016
• Study Completion: November 3, 2016
• Last Updated: August 2, 2019
• Results First Posted: August 2, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)