A Study of a Vaccine for Pneumonia in Adults and Toddlers... | NCT02543892

NCT02543892

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Adult 0.6mg PATH-wSP	Experimental	Two 0.6 mg doses of PATH-wSP with a 28 day interval between doses	Biological: PATH-wSP
Adult Placebo Low Dose	Placebo Comparator	Two injections of normal saline with a 28 day interval between injections	Biological: Placebo
Adult 1.0 mg PATH-wSP	Experimental	Two 1 mg doses of PATH-wSP with a 28 day interval between doses	Biological: PATH-wSP
Adult Placebo High Dose	Placebo Comparator	Two injections of normal saline with a 28 day interval between injections	Biological: Placebo
Toddler 0.6mg PATH-wSP	Experimental	Two 0.6 mg doses of PATH-wSP with a 28 day interval between doses	Biological: PATH-wSP
Toddler Placebo Low Dose	Placebo Comparator	Two injections of normal saline with a 28 day interval between injections

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PATH-wSP	Biological	Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide	Adult 0.6mg PATH-wSP Adult 1.0 mg PATH-wSP

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Highest Grade of Reactogenicity Events in the Adult Cohort: Vaccination 1	Solicited adverse events (AEs) were referred to as reactogenicity events (REs). Local REs included pain, induration/swelling, and erythema/redness at the injection site for adults; and pain/tenderness, redness, and induration/swelling for toddlers. Solicited systemic REs included cutaneous rash, headache, axillary fever/temperature, fatigue/malaise, and arthralgia/myalgia. Solicited REs were assessed for all subjects during the 60 minutes post-vaccination, daily for the first week, and at the clinic visit 1 week post-vaccination. Within the first week post-vaccination, fieldworkers visited the subject at home daily to assess and record solicited reactogenicity and determine whether the subject needed to be seen by the principal investigator (PI) for any medical condition or issue. Generally, grade 1 was no interference with activity, grade 2 was some interference with activity, and grade 3 was prevents daily activity. Grade 0 is equivalent to no event.	7 days after the first dose (Day 7)
Highest Grade of Reactogenicity Events in the Adult Cohort: Vaccination 2	Solicited adverse events (AEs) were referred to as reactogenicity events (REs). Local REs included pain, induration/swelling, and erythema/redness at the injection site for adults; and pain/tenderness, redness, and induration/swelling for toddlers. Solicited systemic REs included cutaneous rash, headache, axillary fever/temperature, fatigue/malaise, and arthralgia/myalgia. Solicited REs were assessed for all subjects during the 60 minutes post-vaccination, daily for the first week, and at the clinic visit 1 week post-vaccination. Within the first week post-vaccination, fieldworkers visited the subject at home daily to assess and record solicited reactogenicity and determine whether the subject needed to be seen by the principal investigator (PI) for any medical condition or issue. Generally, grade 1 was no interference with activity, grade 2 was some interference with activity, and grade 3 was prevents daily activity.	7 days after the second dose (Day 35)
Highest Grade of Reactogenicity Events in the Toddler Cohort: Vaccination 1	Solicited adverse events (AEs) were referred to as reactogenicity events (REs). Local REs included pain, induration/swelling, and erythema/redness at the injection site for adults; and pain/tenderness, redness, and induration/swelling for toddlers. Solicited systemic REs included cutaneous rash, axillary fever/temperature, drowsiness, irritability, and decreased appetite. Solicited REs were assessed for all subjects during the 60 minutes post-vaccination, daily for the first week, and at the clinic visit 1 week post-vaccination. Within the first week post-vaccination, fieldworkers visited the subject at home daily to assess and record solicited reactogenicity and determine whether the subject needed to be seen by the PI for any medical condition or issue. Generally, grade 1 was no interference with activity, grade 2 was some interference with activity, and grade 3 was prevents daily activity. Grade 0 is equivalent to no event.

Secondary Outcomes

Measure	Description	Time Frame
Immunoglobulin G (IgG) Antibody Geometric Mean Concentration Against Pneumococcal Proteins	Proteins were measured on the Meso Scale Discovery (MSD) platform using an an electrochemiluminescence detection assay. Units were arbitrary.	Baseline and 12 weeks after vaccination 2 (Day 0 and Day 112)
Immunoglobulin G (IgG) Antibody Geometric Mean Fold Change Against Pneumococcal Proteins

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy adults who are 18 to 40 years old, or toddlers who are 12 to 19 months old.
Must provide voluntary written/thumb-printed informed consent
Must comply with study requirements and procedures.
Must have an identifiable place of residence to allow home visits, and a consistent means of telephone contact
Must be resident in the study area with no plans to travel outside the study area during the study
Must be willing to not take herbal or other local traditional medications within 28 days of randomization and during the course of the study
Adult female subjects must have a negative serum pregnancy test at screening and urine pregnancy test prior to each vaccination
Toddlers must have been born full-term, and have a mid-upper arm circumference > 11.5 cm at the time of enrollment.
Toddlers must have completed their Kenyan infant EPI schedule through 9 months including 1 birth dose of BCG, 3 doses of DTwPHibHep, 3 doses of OPV (birth dose is not required), 3 doses of PCV, and 1 dose of measles vaccine

Exclusion Criteria:

Use of any investigational or nonregistered drug within 90 days of enrollment
Use of any potentially hepatotoxic drug
Receipt of any licensed vaccine within 14 days of administration of study vaccine.
Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, based on medical history or clinical assessment
History of anaphylactic shock
History of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines
History of immunosuppression or immunodeficiency, inclusive of human immunodeficiency virus (HIV) infection by medical history (including that of an enrolled toddler's mother) or by HIV testing at screening
Evidence of active hepatitis infection (B or C) by serologic testing at screening.
Any screening laboratory test (chemistry or hematology) or vital sign measurement with toxicity grade ≥ 1
Acute illness (moderate or severe) and/or fever (axillary temperature ≥ 37.5°C)
Positive test for malaria (blood film) at screening that remains positive post treatment when retested prior to vaccination
Disorders that require chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within the past 6 months prior to the administration of the study vaccine.
Administration of immunoglobulins and/or any blood products within the 6 months preceding enrollment in the study
Known disturbance of coagulation or other blood disorder (e.g., thalassemia, sickle cell disease, thrombocytopenia, disorders of the lymphocytes, severe anemia at birth) in adult subject or in self/first-degree relative of toddler subject; or receipt of anticoagulants in the past three weeks (aspirin as needed and nonsteroidal anti-inflammatory drugs are acceptable)
History of meningitis, seizures or any neurological disorder (all participants) or major psychiatric disorder (adults)
Any medical or social condition that in the opinion of the investigator will interfere with the study objectives or pose a risk to the study subject
An employee (or first-degree relative of employee) of the Sponsor, the CRO, or any investigator or site personnel
Female adult subjects who are pregnant or breast-feeding
Adults with a recent history (within the past year) of alcohol or substance abuse.
Toddlers who have already received a pentavalent booster (following the primary series).
Toddlers with a family history of suspected primary immunodeficiency in first-degree relative.
Toddlers who had a sibling die of likely sudden infant death syndrome (SIDS) or die suddenly and without apparent other cause or preceding illness in the first year of life.
Toddlers with evidence of a clinically significant congenital abnormality as judged by the PI.
Toddlers with evidence of fetal alcohol syndrome or maternal history of alcohol abuse during pregnancy

Name	Affiliation	Role
Anthony Scott, MD	London School of Hygiene and Tropical Medicine	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
KEMRI-Wellcome Trust Research Programme; Centre for Geographic Medicine Research - Coast		Kilifi		80108	Kenya

Arm/Group Information

ID	Title	Description
FG000	Adult 0.6mg PATH-wSP	Two 0.6 mg doses of PATH-wSP with a 28 day interval between doses PATH-wSP: Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide
FG001	Adult 1.0 mg PATH-wSP	Two 1 mg doses of PATH-wSP with a 28 day interval between doses PATH-wSP: Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide
FG002	Adult Placebo Low Dose	Two injections of normal saline with a 28 day interval between injections Placebo: Normal Saline
FG003	Adult Placebo High Dose	Two injections of normal saline with a 28 day interval between injections Placebo: Normal Saline
FG004	Toddler 0.6mg PATH-wSP	Two 0.6 mg doses of PATH-wSP with a 28 day interval between doses PATH-wSP: Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide
FG005	Toddler 1.0 mg PATH-wSP	Two 1 mg doses of PATH-wSP with a 28 day interval between doses PATH-wSP: Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide
FG006	Toddler Placebo Low Dose	Two injections of normal saline with a 28 day interval between injections Placebo: Normal Saline
FG007	Toddler Placebo High Dose	Two injections of normal saline with a 28 day interval between injections Placebo: Normal Saline

ID	Title	Description
BG000	Adult 0.6mg PATH-wSP	Two 0.6 mg doses of PATH-wSP with a 28 day interval between doses PATH-wSP: Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide
BG001	Adult 1.0 mg PATH-wSP

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Highest Grade of Reactogenicity Events in the Adult Cohort: Vaccination 1

Solicited adverse events (AEs) were referred to as reactogenicity events (REs). Local REs included pain, induration/swelling, and erythema/redness at the injection site for adults; and pain/tenderness, redness, and induration/swelling for toddlers. Solicited systemic REs included cutaneous rash, headache, axillary fever/temperature, fatigue/malaise, and arthralgia/myalgia. Solicited REs were assessed for all subjects during the 60 minutes post-vaccination, daily for the first week, and at the clinic visit 1 week post-vaccination. Within the first week post-vaccination, fieldworkers visited the subject at home daily to assess and record solicited reactogenicity and determine whether the subject needed to be seen by the principal investigator (PI) for any medical condition or issue. Generally, grade 1 was no interference with activity, grade 2 was some interference with activity, and grade 3 was prevents daily activity. Grade 0 is equivalent to no event.

Posted

Count of Participants

Participants

7 days after the first dose (Day 7)

ID	Title	Description

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Adult 0.6mg PATH-wSP	Two 0.6 mg doses of PATH-wSP with a 28 day interval between doses PATH-wSP: Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 3, 2017	Aug 31, 2018	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jan 11, 2018	Aug 31, 2018	SAP_001.pdf

ID	Term
D012141	Respiratory Tract Infections
D007239	Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases