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Report for Clinical Trial NCT02097472

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Dose-Finding Study to Assess the Safety, Tolerability, and Immunogenicity of Inactivated Streptococcus Pneumoniae Whole Cell Vaccine Formulated With Alum (PATH-wSP) in Healthy Kenyan Young Adults and PCV-Primed Toddlers

The purpose of this study is to assess the safety and tolerability of PATH-wSP, administered intramuscularly to healthy Kenyan adults and toddlers who have been primed with a pneumococcal conjugate vaccine (PCV). Additionally, the study will explore whether a measurable immune response is elicited when PATH-wSP is administered to healthy Kenyan adults and toddlers who have been primed with PCV.

NCT02097472 Pneumonia, Pneumococcal
MeSH: Pneumonia, Pneumococcal Pneumonia
HPO: Pneumonia

4 Interventions

Name: PATH-wSP

Description: Streptococcus pneumoniae Whole Cell Vaccine adsorbed to Alum

Type: Biological

Adult Cohort 1, PATH-wSP, 600 mcg Adult Cohort 2, PATH-wSP, 1000 mcg Toddler Cohort 1 PATH-wSP 300 mcg+Active control Toddler Cohort 1 PATH-wSP 300 mcg+Saline Toddler Cohort 2 PATH-wSP 600 mcg+Active control Toddler Cohort 2 PATH-wSP 600 mcg+saline

Name: Synflorix

Description: 1 dose (0.5 mL) contains: 1 μg of each of the following pneumococcal polysaccharide serotypes: 1, 5, 6B, 7F, 9V, 14, and 23 F And 3 μg of the following pneumococcal polysaccharide serotypes: 4, 18C and 19F. The serotypes are conjugated to either: protein D (derived from Non-Typeable Haemophilus influenzae) carrier protein, tetanus toxoid carrier protein or diphtheria toxoid carrier protein

Type: Biological

Toddler Cohort 1 PATH-wSP 300 mcg+Active control Toddler Cohort 1: Active Control Only Toddler Cohort 2 PATH-wSP 600 mcg+Active control Toddler Cohort 2: Active Control Only

Name: Pentavac

Description: Each PFS contains 0.5 ml (single dose): Diphtheria Toxoid 20 Lf to 30 Lf Tetanus Toxoid 2.5 Lf to 10 Lf B. Pertussis 4 IU HBsAg (rDNA) 10 mcg Purified capsular HIB Polysaccharide (PRP) Conjugated to Tetanus Toxoid (carrier protein) 10 mcg Adsorbed on Aluminium Phosphate, AL+++ 1.25 mg Preservative: Thiomersal 0.005 % Dose: O.5ml by intramuscular injection.

Type: Biological

Toddler Cohort 1 PATH-wSP 300 mcg+Active control Toddler Cohort 1: Active Control Only Toddler Cohort 2 PATH-wSP 600 mcg+Active control Toddler Cohort 2: Active Control Only

Name: Saline

Description: 0.9% Sodium Chloride Injection, USP

Type: Other

Adult Cohort 1, Saline Adult Cohort 2, Saline Toddler Cohort 1 PATH-wSP 300 mcg+Saline Toddler Cohort 1: Active Control Only Toddler Cohort 2 PATH-wSP 600 mcg+saline Toddler Cohort 2: Active Control Only


Primary Outcomes

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.

Measure: Number/Percent of Adult Subjects Experiencing Fatigue/Malaise Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.

Measure: Number/Percent of Adult Subjects Experiencing Myalgia Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Grade 2 includes repeated use of non-narcotic pain reliever for more than 24 hours.

Measure: Number/Percent of Adult Subjects Experiencing Headache Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Grade 2 includes use of non-narcotic pain reliever for more than 24 hours.

Measure: Number/Percent of Adult Subjects Experiencing Pain at Injection Site Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.

Measure: Number/Percent of Adult Subjects Experiencing Tenderness at Injection Site Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Grade 1: does not interfere with activity Grade 2: interferes with activity

Measure: Number/Percent of Adult Subjects Experiencing Induration at Injection Site Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.

Measure: Number/Percent of Adult Subjects Experiencing Fever at Injection Site Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.

Measure: Number/Percent of Toddler Subjects Experiencing Fever Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Grade 2: includes diffuse macular/maculopapular/morbilliform rash

Measure: Number/Percent of Toddler Subjects Experiencing Cutaneous Rash Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).

Measure: Number/Percent of Toddler Subjects Experiencing Irritability Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).

Measure: Number/Percent of Toddler Subjects Experiencing Drowsiness Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).

Measure: Number/Percent of Toddler Subjects Experiencing Loss of Appetite Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination.

Measure: Number/Percent of Toddler Subjects Experiencing Pain/Tenderness at Injection Site Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Description: Solicited reactions were assessed for severity during the 60 minutes post vaccination time period, daily for the first week by Field Staff and then at the clinic visit 1 week post vaccination. Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).

Measure: Number/Percent of Toddler Subjects Experiencing Induration/Swelling at Injection Site Following Vaccination

Time: up to 1 week following first vaccination (Day 7) or second vaccination (Day 35)

Secondary Outcomes

Description: Measured with enzyme-linked immunosorbent assay (ELISA).

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA Assay

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured with enzyme-linked immunosorbent assay (ELISA).

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: ELISA Assay

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using meso scale discovery (MSD).

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against L460D Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: Meso Scale Discovery (MSD) Assay

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using Meso Scale Discovery (MSD) Assay

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PhtD Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using Meso Scale Discovery (MSD) Assay

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against BCH0785 Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using Meso Scale Discovery (MSD) Assay

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against StkP Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using Meso Scale Discovery (MSD) Assay

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PcpA Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: MSD Assay

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against SPWCA Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: MSD Assay

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PiuA Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: MSD Assay

Measure: Geometric Mean Concentrations (GMC) of IgG Antibodies Against PiaA Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using ELISA

Measure: Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using ELISA

Measure: Geometric Mean Fold Change of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: ELISA

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using MSD

Measure: Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: MSD

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using ELISA

Measure: Geometric Mean Fold Change of IgG Antibodies Against PspA-Fam1 Pneumococcal Protein: MSD

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using MSD

Measure: Geometric Mean Fold Change of IgG Antibodies Against PhtD Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using MSD

Measure: Geometric Mean Fold Change of IgG Antibodies Against BCH0785 Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using MSD

Measure: Geometric Mean Fold Change of IgG Antibodies Against StkP Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using MSD

Measure: Geometric Mean Fold Change of IgG Antibodies Against PcpA Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using MSD

Measure: Geometric Mean Fold Change of IgG Antibodies Against SPWCA Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using MSD

Measure: Geometric Mean Fold Change of IgG Antibodies Against PiuA Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using MSD

Measure: Geometric Mean Fold Change of IgG Antibodies Against PiaA Pneumococcal Protein

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Measured using ELISA

Measure: Fold Change in IgG Response to Pneumolysoid (L460D) Pneumococcal Protein Among Toddler Cohort (ELISA)

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using ELISA

Measure: Fold Change in IgG Response to PspA-Fam1 (ELISA)

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to L460D Pneumococcal Protein (MSD)

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to PspA-Fam1 Pneumococcal Protein (MSD)

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to PhtD Pneumococcal Protein

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to BCH0785 Pneumococcal Protein

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to StkP Pneumococcal Protein

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to PcpA Pneumococcal Protein

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to SPWCA Pneumococcal Protein

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to PiuA Pneumococcal Protein

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Measured using MSD

Measure: Fold Change in IgG Response to PiaA Pneumococcal Protein

Time: 28 days (post-vaccination 1) and 56 days (post-vaccination 2)

Description: Functional antibody responses to Ply (pneumolysin) were assessed using a toxin neutralization assay based on the ability of antibodies to neutralize wild-type Ply-induced lysis of rabbit red blood cells. Briefly, serial 2-fold dilutions (starting at 1/5 dilution) of human serum samples were added together with wild-type Ply in 96-well plates. Rabbit red blood cells were then added and following incubation supernatants removed and transferred to new 96-well plates and absorbance measured at 540 nm using a spectrophotometer plate reader. The mean A450 nm blank value was subtracted by 10% to obtain the Plate Specific Cut Point for each plate. Each sample was categorized as negative (<1/20) or positive (with titer between 1/20 and 1/320).

Measure: Number/Percentage of Adult Subjects With Neutralizing Antibody Response to Pneumolysin

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Description: Functional antibody responses to Ply (pneumolysin) were assessed using a toxin neutralization assay based on the ability of antibodies to neutralize wild-type Ply-induced lysis of rabbit red blood cells. Briefly, serial 2-fold dilutions (starting at 1/5 dilution) of human serum samples were added together with wild-type Ply in 96-well plates. Rabbit red blood cells were then added and following incubation supernatants removed and transferred to new 96-well plates and absorbance measured at 540 nm using a spectrophotometer plate reader. The mean A450 nm blank value was subtracted by 10% to obtain the Plate Specific Cut Point for each plate. Each sample was categorized as negative (<1/20) or positive (with titer between 1/20 and 1/320).

Measure: Number/Percentage of Toddler Subjects With Neutralizing Antibody Response to Pneumolysin

Time: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Other Outcomes

Description: GMCs of these IgG proteins were measured to assess potential interference of PATH-wSP with 10-valent pneumococcal conjugate vaccine (Synflorix). GMCs of Cohort 1 were measured at a different time point than those in Cohort 2, so results are presented separately.

Measure: Geometric Mean Concentration (GMCs) of PNC-IgG Serotypes Among Toddler Subjects

Time: 12 weeks (Cohort 1) and 4 weeks (Cohort 2) post-vaccination 1

Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.

Measure: Geometric Mean Concentration (GMC) Ratio of Diptheria Booster Immune Response Among Toddler Subjects

Time: 12 weeks post vaccination 1

Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.

Measure: Geometric Mean Concentration (GMC) Ratio of Hepatitis B Booster Immune Response Among Toddler Subjects

Time: 12 weeks post vaccination 1

Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.

Measure: Geometric Mean Concentration (GMC) Ratio of Haemophilus Influenzae Type b (Hib) Booster Immune Response Among Toddler Subjects

Time: 12 weeks post vaccination 1

Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.

Measure: Geometric Mean Concentration (GMC) Ratio of Pertussis FHA and Pertussis Toxin Immune Response Among Toddler Subjects

Time: 12 weeks post vaccination 1

Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.

Measure: Geometric Mean Concentration (GMC) Ratio of Pertussis Fimbriae Immune Response Among Toddler Subjects

Time: 12 weeks post vaccination 1

Description: GMCs of these proteins were measured to assess potential interference of PATH-wSP with Pentavac booster dose.

Measure: Geometric Mean Concentration (GMC) Ratio of Tetanus Booster Immune Response Among Toddler Subjects

Time: 12 weeks post vaccination 1

Purpose: Prevention

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 L460D

Severity was defined in the protocol as grade 0-4 (none, mild, moderate, and severe).. Geometric Mean Concentrations (GMC) of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA Assay. --- L460D ---

Measured with enzyme-linked immunosorbent assay (ELISA).. Geometric Mean Concentrations (GMC) of IgG Antibodies Against L460D Pneumococcal Protein. --- L460D ---

Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: ELISA. --- L460D ---

Geometric Mean Fold Change of IgG Antibodies Against Pneumolysoid (L460D) Pneumococcal Protein: MSD. --- L460D ---

Fold Change in IgG Response to Pneumolysoid (L460D) Pneumococcal Protein Among Toddler Cohort (ELISA). --- L460D ---

Fold Change in IgG Response to L460D Pneumococcal Protein (MSD). --- L460D ---



HPO Nodes


HPO:
Pneumonia
Genes 208
TIMM8A DNAH9 GAS8 DNAH11 TNFRSF11A TBC1D24 SPAG1 MS4A1 GAS2L2 CCDC151 NIPBL BTK LIG4 NFKB2 TCIRG1 IGLL1 RNF168 STAT3 TAF1 RSPH4A CFTR NME8 DNAAF4 LEP CCDC65 NADK2 CD55 COL11A2 NHLRC1 PEPD CFAP300 LTBP3 WAS DNAI1 TBCD IL2RG GFI1 NBN RSPH1 CCDC39 PMM2 ICOS TNFSF12 IFNGR1 CARD11 SFTPC DNAL1 OFD1 ZMYND10 IL21R FMO3 SLC35A1 PLOD1 ORC6 RAG2 CACNA1C GAS8 RYR1 CFAP298 GNPTAB TNFRSF13B KDM6A PANK2 RANBP2 CYBA USB1 UBB DOCK8 ADA DNAAF2 KMT2D SAMD9 MUC5B IL7R DNAAF1 ICOS RAG2 CARD11 PTPRC ALMS1 NOTCH3 NSMCE3 DNAI1 TNFRSF13C GRHL3 EGFR IL2RG DNAAF6 PNP DNAH5 SETBP1 CR2 CD3E ADA MASP2 SFTPA2 ACTA1 RAC1 TTC25 FCGR2A ZAP70 SPEF2 IGHM DNAAF5 NBN CD247 DDR2 CD19 ACADVL KIAA0586 TK2 BLNK ARMC4 SGCG RAG1 CXCR4 NCF1 SRP54 FOXP3 IRF8 CFAP221 RNU4ATAC KCNJ6 LRBA CD3D P4HTM SELENON CCDC114 TNFRSF13B PLG DCLRE1C SLC25A24 DCLRE1C ICOS IL7R FOXJ1 JAK3 IL2RG CASP8 RAG1 OSTM1 CFAP410 CCNO NCF2 UNC119 TNFRSF13C JAK3 RNF125 STK36 POLA1 CD19 CR2 DNAH1 RSPH3 RSPH9 CYBB DRC1 DCLRE1C CCDC103 DNAAF3 LRRC56 PIGN LRRC6 SP110 PRKCD ACP5 CCDC40 SLC35C1 BTK MTHFD1 PGM3 RAG1 TERT CHD7 CFB TGFB1 RNU4ATAC SMARCD2 NKX2-1 OFD1 ZBTB24 BTK DNAI2 WDR19 ZAP70 CD79B CD81 COL11A2 NFIX RAG2 ELANE AFF4 NFKB1 IL2RG TNFRSF13C TNFSF12 CCDC114 ADA GBA DNAJB13 RPGR CSPP1 RMRP EPM2A DNMT3B NFKB2 MCIDAS HYDIN