Pneumococcal DiseasePhase 1/2NCT02308540
Safety and Immunogenicity of a 10 Valent Pneumococcal Conjugate Vaccine (SIILPCV10) in Healthy Adults, Toddlers, Infants
A Phase 1/2 study testing SIILPCV10, Pneumovax 23 and Prevenar 13 in people with Pneumococcal Disease, run by PATH at 1 site in The Gambia.
Trial 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… Read more about this study
- Who is it for?
- Ages 4 weeks to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Pneumococcal Disease
- What is being tested?
- SIILPCV10, Pneumovax 23 and Prevenar 13
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 346 participants
- Where
- 1 siteThe Gambia
- Study dates
- 12 Jan 2015to 3 Nov 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 weeks to 40 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- • 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
This was a prospective, single-center, randomized, active-controlled, double-blind, age de escalation study in healthy Gambian PCV-naïve adults (18-40 years old), PCV primed toddlers (12-15 months old) and PCV-naïve infants (6-8 weeks old).
In the adult cohort, at least 34 eligible PCV-naïve adults (18-40 years old) were planned to be randomized into the study to receive a single dose of either SIILPCV10 or Pneumovax 23 in a 1:1 ratio on Day 0 (V1), with stratification by sex (although no fixed proportion of males and females was required in the cohort as a whole).
In the toddler cohort, at least 112 eligible PCV-primed toddlers (12-15 months old) were planned to be randomized into the study to receive a single dose of either SIILPCV10 or Prevenar 13 in a 1:1 ratio on Day 0 (V1).
Each adult and toddler subject underwent a total of 4 clinic visits, including at least 1 screening visit (V0) no more than 14 days prior to Day 0, a vaccination visit on Day 0 (V1), and follow-up clinic visits at 7 (+3) and 28 (+14) days after vaccination (V2 and V3, respectively). A total of 3 blood samples were obtained for laboratory safety and immunogenicity assessments.
In the infant cohort, at least 200 eligible PCV-naïve infants (6 to 8 weeks old) were randomized into the study to receive 3 doses of either SIILPCV10 or Prevenar 13 in a 1:1 ratio along with standard Expanded Program on Immunisation (EPI) vaccinations (pentavalent diphtheria, tetanus, whole-cell pertussis, hepatitis B, and Haemophilus influenzae type b combined vaccine [DTwP-HepB-Hib], oral poliovirus vaccine [OPV], rotavirus vaccine [RV], and inactivated poliovirus vaccine [IPV]).
Each infant subject underwent a total of 9 scheduled visits for the primary series: at least 1 screening visit (V0); 3 primary vaccination visits at 28 (+14)-day intervals (V1, 3, 5); follow-up clinic visits at 7 (+3) days after each primary vaccination (V2, 4, 6); and 2 follow-up visits 28 and 84 days after the last primary vaccination (V7 and V8, respectively). Windows for follow-up and subsequent vaccination visits were calculated based on the actual calendar date of the prior vaccination, rather than relative to the day of randomization. Vaccinations included the blinded PCV study vaccine (SIILPCV10 or Prevenar 13) and the unblinded EPI vaccines (DTwP-HepB-Hib, OPV, RV, and IPV).
A total of 2 blood samples were obtained for the primary series (V0 and V7), with the first sample used for safety laboratory eligibility assessment, and if randomized, for baseline immunogenicity testing. Immunogenicity testing was also done on the second sample.
During the supplemental booster phase, infant subjects underwent 2 additional visits: a fourth (booster) vaccination visit (V9) at ≥ 9 months of age, and a follow-up visit 28 days after the booster dose (V10). The EPI vaccines scheduled for 9 months of age in The Gambia were not given as part of the study. However, study personnel contacted parents of infant subjects to remind them of the need to attend this EPI vaccination visit at the due date to allow for effective scheduling of the subsequent booster. The vaccine (SIILPCV10 or Prevenar 13) was given at least 4 weeks after the routine EPI vaccines given at 9 months of age in The Gambia (measles and rubella, yellow fever, and OPV). Infants who received SIILPCV10 at V9 were offered a booster dose of Prevenar 13 at least 56 days following the SIILPCV10 boost. Immunogenicity testing was performed on 2 additional blood samples collected during the booster phase (V9 and V10).
In the adult and toddler cohorts, on the day of vaccination, a malaria rapid test was performed using a finger prick to rule out parasitemia and a urine pregnancy test was performed (in adult women who were not surgically sterile) to rule out pregnancy before final eligibility was confirmed and randomization occurred. In the infant cohort, on each day of vaccination, a malaria rapid test was performed using a finger prick to rule out parasitemia before vaccination occurred. Any infant showing signs of acute illness or abnormal vital signs on the day of vaccination were not vaccinated until recovery was documented by the study team.
After all vaccinations, subjects were monitored for solicited reactogenicity. All adult and toddler subjects were monitored for AEs at each clinic visit until V3, and ongoing AEs at study exit were followed until last subject last visit (LSLV). Infant subjects were monitored for AEs at each clinic visit until V8. For infants who participated in the booster phase of the study, AEs were recorded at V10, and any conditions present at V9 were considered baseline.
SAS software was used to analyze data.
- Conditions
- Pneumococcal Disease
- Being tested
- SIILPCV10, Pneumovax 23, Prevenar 13
- Medical subject headings
- Pneumococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SIILPCV10Biological
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).
Pneumovax 23Biological
Also called 23-valent Pneumococcal Polysaccharide Vaccine
23-valent Pneumococcal Polysaccharide Vaccine (Pneumovax 23; MSD Pharmaceuticals) for the adult cohort.
Prevenar 13Biological
Also called 13-valent Pneumococcal Conjugate Vaccine
13-valent Pneumococcal Conjugate Vaccine (Prevenar 13; Pfizer-Wyeth) for the toddler and infant cohorts
| Study group | Role | What they receive |
|---|---|---|
| Adult SIILPCV10 | Experimental | Single dose of SIILPCV10 on day 0 Receives: Biological: SIILPCV10 |
| Adult Pneumovax 23 | Active comparator | Single dose of Pneumovax 23 on day 0 Receives: Biological: Pneumovax 23 |
| Toddler SIILPCV10 | Experimental | Single dose of SIILPCV10 on day 0 Receives: Biological: SIILPCV10 |
| Toddler Prevenar 13 | Active comparator | Single dose of Prevenar 13 on day 0 Receives: Biological: Prevenar 13 |
| Infants SIIL PCV10 | Experimental | A three-dose series of SIILPCV10 on day 0, day 28, and day 56 Receives: Biological: SIILPCV10 |
| Infants Prevenar 13 | Active comparator | A three-dose series of Prevenar 13 on day 0, day 28, and day 56 Receives: Biological: Prevenar 13 |
| Infant Booster Dose SIILPCV 10 | Experimental | One dose of SIILPCV 10 at 9 months of age Receives: Biological: SIILPCV10 |
| Infant Booster Dose Prevenar 13 | Active comparator | One dose of SIILPCV 10 at 9 months of age Receives: Biological: Prevenar 13 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 7 days after vaccination
Secondary outcomes (8)
Geometric Mean Concentration of Immunoglobulin G (IgG) for Adults
Serum samples were collected 28 days after the vaccination in adults to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10.
Measured: 4 weeks after vaccination
Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Toddlers
Serum samples were collected 28 days after vaccination for toddlers to determine the ELISA IgG concentration for all 10 serotypes contained in SIILPCV10.
Measured: 4 weeks after vaccination
Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Infants
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.
Measured: 4 weeks after the third dose
Geometric Mean Fold Rise (GMFR) of Immunoglobulin G (IgG) in Toddlers, by Serotype
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.
Measured: 4 weeks after vaccination (28 days)
Number and Percentage of Immunoglobulin G (IgG) Seroresponders Among Infants, by Serotype
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.
Measured: 4 weeks after third dose
Functional Antibody (OPA) Geometric Mean Titers
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.
Measured: 4 weeks after last vaccination
Number and Percentage of Functional (OPA) Infant Seroresponders, by Serotype
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.
Measured: 84 days
Number and Percentage of Immunoglobulin G (IgG) Seroresponders Against Pentavalent Vaccine Components
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
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study start12 Jan 2015
- Primary completionApr 2016
- Study completion3 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pneumococcal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 346 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ed Clarke, MD PhD, Principal investigator, Medical Research Council (MRC) Unit, The Gambia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02308540
- Sponsor's protocol ID
- VAC-017
- Status last verified
- Jun 2019
- First submitted
- 24 Nov 2014
- Last updated
- 2 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31843266
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02308540
- Acronym / sponsor ID
- VAC-017
- Conditions
- Pneumococcal Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 346 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Study start
- 12 Jan 2015 (actual)
- Primary completion
- Apr 2016 (actual)
- Study completion
- 3 Nov 2016 (actual)
- First posted
- 4 Dec 2014 (estimated)
- Results
- Posted 2 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This was a prospective, single-center, randomized, active-controlled, double-blind, age de escalation study in healthy Gambian PCV-naïve adults (18-40 years old), PCV primed toddlers (12-15 months old) and PCV-naïve infants (6-8 weeks old).
In the adult cohort, at least 34 eligible PCV-naïve adults (18-40 years old) were planned to be randomized into the study to receive a single dose of either SIILPCV10 or Pneumovax 23 in a 1:1 ratio on Day 0 (V1), with stratification by sex (although no fixed proportion of males and females was required in the cohort as a whole).
In the toddler cohort, at least 112 eligible PCV-primed toddlers (12-15 months old) were planned to be randomized into the study to receive a single dose of either SIILPCV10 or Prevenar 13 in a 1:1 ratio on Day 0 (V1).
Each adult and toddler subject underwent a total of 4 clinic visits, including at least 1 screening visit (V0) no more than 14 days prior to Day 0, a vaccination visit on Day 0 (V1), and follow-up clinic visits at 7 (+3) and 28 (+14) days after vaccination (V2 and V3, respectively). A total of 3 blood samples were obtained for laboratory safety and immunogenicity assessments.
In the infant cohort, at least 200 eligible PCV-naïve infants (6 to 8 weeks old) were randomized into the study to receive 3 doses of either SIILPCV10 or Prevenar 13 in a 1:1 ratio along with standard Expanded Program on Immunisation (EPI) vaccinations (pentavalent diphtheria, tetanus, whole-cell pertussis, hepatitis B, and Haemophilus influenzae type b combined vaccine [DTwP-HepB-Hib], oral poliovirus vaccine [OPV], rotavirus vaccine [RV], and inactivated poliovirus vaccine [IPV]).
Each infant subject underwent a total of 9 scheduled visits for the primary series: at least 1 screening visit (V0); 3 primary vaccination visits at 28 (+14)-day intervals (V1, 3, 5); follow-up clinic visits at 7 (+3) days after each primary vaccination (V2, 4, 6); and 2 follow-up visits 28 and 84 days after the last primary vaccination (V7 and V8, respectively). Windows for follow-up and subsequent vaccination visits were calculated based on the actual calendar date of the prior vaccination, rather than relative to the day of randomization. Vaccinations included the blinded PCV study vaccine (SIILPCV10 or Prevenar 13) and the unblinded EPI vaccines (DTwP-HepB-Hib, OPV, RV, and IPV).
A total of 2 blood samples were obtained for the primary series (V0 and V7), with the first sample used for safety laboratory eligibility assessment, and if randomized, for baseline immunogenicity testing. Immunogenicity testing was also done on the second sample.
During the supplemental booster phase, infant subjects underwent 2 additional visits: a fourth (booster) vaccination visit (V9) at ≥ 9 months of age, and a follow-up visit 28 days after the booster dose (V10). The EPI vaccines scheduled for 9 months of age in The Gambia were not given as part of the study. However, study personnel contacted parents of infant subjects to remind them of the need to attend this EPI vaccination visit at the due date to allow for effective scheduling of the subsequent booster. The vaccine (SIILPCV10 or Prevenar 13) was given at least 4 weeks after the routine EPI vaccines given at 9 months of age in The Gambia (measles and rubella, yellow fever, and OPV). Infants who received SIILPCV10 at V9 were offered a booster dose of Prevenar 13 at least 56 days following the SIILPCV10 boost. Immunogenicity testing was performed on 2 additional blood samples collected during the booster phase (V9 and V10).
In the adult and toddler cohorts, on the day of vaccination, a malaria rapid test was performed using a finger prick to rule out parasitemia and a urine pregnancy test was performed (in adult women who were not surgically sterile) to rule out pregnancy before final eligibility was confirmed and randomization occurred. In the infant cohort, on each day of vaccination, a malaria rapid test was performed using a finger prick to rule out parasitemia before vaccination occurred. Any infant showing signs of acute illness or abnormal vital signs on the day of vaccination were not vaccinated until recovery was documented by the study team.
After all vaccinations, subjects were monitored for solicited reactogenicity. All adult and toddler subjects were monitored for AEs at each clinic visit until V3, and ongoing AEs at study exit were followed until last subject last visit (LSLV). Infant subjects were monitored for AEs at each clinic visit until V8. For infants who participated in the booster phase of the study, AEs were recorded at V10, and any conditions present at V9 were considered baseline.
SAS software was used to analyze data.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Adult SIILPCV10 | Experimental | Biological: SIILPCV10Single dose of SIILPCV10 on day 0 |
| Adult Pneumovax 23 | Active comparator | Biological: Pneumovax 23Single dose of Pneumovax 23 on day 0 |
| Toddler SIILPCV10 | Experimental | Biological: SIILPCV10Single dose of SIILPCV10 on day 0 |
| Toddler Prevenar 13 | Active comparator | Biological: Prevenar 13Single dose of Prevenar 13 on day 0 |
| Infants SIIL PCV10 | Experimental | Biological: SIILPCV10A three-dose series of SIILPCV10 on day 0, day 28, and day 56 |
| Infants Prevenar 13 | Active comparator | Biological: Prevenar 13A three-dose series of Prevenar 13 on day 0, day 28, and day 56 |
| Infant Booster Dose SIILPCV 10 | Experimental | Biological: SIILPCV10One dose of SIILPCV 10 at 9 months of age |
| Infant Booster Dose Prevenar 13 | Active comparator | Biological: Prevenar 13One dose of SIILPCV 10 at 9 months of age |
Who may qualify
- Ages
- 4 weeks to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- • Healthy adults (18-40 yrs), toddlers (12-15 mo), full term infants (6-8 wks) and ≥ 3.5 kg
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SIILPCV1010-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). | Biological | Adult SIILPCV10, Infant Booster Dose SIILPCV 10, Infants SIIL PCV10, Toddler SIILPCV10 |
| Pneumovax 23Also: 23-valent Pneumococcal Polysaccharide Vaccine23-valent Pneumococcal Polysaccharide Vaccine (Pneumovax 23; MSD Pharmaceuticals) for the adult cohort. | Biological | Adult Pneumovax 23 |
| Prevenar 13Also: 13-valent Pneumococcal Conjugate Vaccine13-valent Pneumococcal Conjugate Vaccine (Prevenar 13; Pfizer-Wyeth) for the toddler and infant cohorts | Biological | Infant Booster Dose Prevenar 13, Infants Prevenar 13, Toddler Prevenar 13 |
Primary outcome
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).
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).
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).
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).
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.
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.
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.
8 secondary outcomes
Geometric Mean Concentration of Immunoglobulin G (IgG) for Adults
Time frame: 4 weeks after vaccination
Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Toddlers
Time frame: 4 weeks after vaccination
Geometric Mean Concentration of Immunoglobulin G (IgG) 4 Weeks After Vaccination for Infants
Time frame: 4 weeks after the third dose
Geometric Mean Fold Rise (GMFR) of Immunoglobulin G (IgG) in Toddlers, by Serotype
Time frame: 4 weeks after vaccination (28 days)
Number and Percentage of Immunoglobulin G (IgG) Seroresponders Among Infants, by Serotype
Time frame: 4 weeks after third dose
Functional Antibody (OPA) Geometric Mean Titers
Time frame: 4 weeks after last vaccination
Number and Percentage of Functional (OPA) Infant Seroresponders, by Serotype
Time frame: 84 days
Number and Percentage of Immunoglobulin G (IgG) Seroresponders Against Pentavalent Vaccine Components
Time frame: 84 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31843266Clarke 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ed Clarke, MD PhD principal investigator
Medical Research Council (MRC) Unit, The Gambia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SIILPCV10, Pneumovax 23 and Prevenar 13 in people with Pneumococcal Disease, run by PATH at 1 site in The Gambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in The Gambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adult and Toddler Subjects Experiencing Local and Systemic Reactogenicity, by Severity (time frame: 7 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02308540, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2019.