Dose-Finding Study of S.Pneumoniae Whole Cell Vaccine Adsorbed to Alum (PATH-wSP) in Healthy Kenyan Adults and Toddlers

NCT02097472 | Completed Phase 1 Results DMC

• 1 other identifier: VAC-010
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pneumonia, Pneumococcal

Outcome Measures

Primary Outcomes (14)

• Number/Percent of Adult Subjects Experiencing Fatigue/Malaise Following Vaccination

  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.

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

• Number/Percent of Adult Subjects Experiencing Myalgia Following Vaccination

  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.

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

• Number/Percent of Adult Subjects Experiencing Headache Following Vaccination

  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.

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

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

  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.

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

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

  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.

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

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

  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

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

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

  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.

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

• Number/Percent of Toddler Subjects Experiencing Fever Following Vaccination

  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.

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

• Number/Percent of Toddler Subjects Experiencing Cutaneous Rash Following Vaccination

  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

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

• Number/Percent of Toddler Subjects Experiencing Irritability Following Vaccination

  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).

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

• Number/Percent of Toddler Subjects Experiencing Drowsiness Following Vaccination

  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).

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

• Number/Percent of Toddler Subjects Experiencing Loss of Appetite Following Vaccination

  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).

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

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

  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.

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

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

  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).

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

Secondary Outcomes (35)

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

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

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

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

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

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

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

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

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

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

Other Outcomes (7)

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

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

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

  12 weeks post vaccination 1

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

  12 weeks post vaccination 1

Study Arms (10)

Adult Cohort 1, PATH-wSP, 600 mcg

EXPERIMENTAL

A single injection of 600 mcg PATH-wSP in one arm, followed 4 weeks later by a single injection of 600 mcg PATH-wSP in the alternate arm.

Biological: PATH-wSP

Adult Cohort 1, Saline

PLACEBO COMPARATOR

A single injection of saline in one arm, followed 4 weeks later by a single injection of saline in the alternate arm.

Other: Saline

Adult Cohort 2, PATH-wSP, 1000 mcg

EXPERIMENTAL

A single injection of 1000 mcg PATH-wSP in one arm, followed 4 weeks later by a single injection of 1000 mcg PATH-wSP in the alternate arm.

Biological: PATH-wSP

Adult Cohort 2, Saline

PLACEBO COMPARATOR

A single injection of saline in one arm, followed 4 weeks later by a single injection of saline in the alternate arm.

Other: Saline

Toddler Cohort 1 PATH-wSP 300 mcg+Active control

EXPERIMENTAL

A single injection of PATH-wSP 300 mcg in the left thigh and a single injection of each of the two active comparator vaccines (Synflorix and Pentavac) in the right thigh. These 3 injections are followed by a single injection of PATH-wSP 300 mcg in the left thigh 8 weeks later.

Biological: PATH-wSP; Biological: Synflorix; Biological: Pentavac

Toddler Cohort 1 PATH-wSP 300 mcg+Saline

EXPERIMENTAL

A single injection of PATH-wSP 300 mcg in the left thigh and a single injection of saline in the right thigh along with a separate single injection of saline in the right thigh. These 3 injections are followed by a single injection of PATH-wSP 300 mcg in the left thigh 8 weeks later.

Biological: PATH-wSP; Other: Saline

Toddler Cohort 1: Active Control Only

ACTIVE COMPARATOR

A single injection of saline in the left thigh and a single injection of each of the two active comparator vaccines (Synflorix and Pentavac) in the right thigh. These 3 injections are followed by a single injection of saline in the left thigh 8 weeks later.

Biological: Synflorix; Biological: Pentavac; Other: Saline

Toddler Cohort 2 PATH-wSP 600 mcg+Active control

EXPERIMENTAL

A single injection of PATH-wSP 600 mcg in the left thigh and a single injection of each of the two active comparator vaccines (Synflorix and Pentavac) in the right thigh. These 3 injections are followed by a single injection of PATH-wSP 600 mcg in the left thigh 8 weeks later.

Biological: PATH-wSP; Biological: Synflorix; Biological: Pentavac

Toddler Cohort 2 PATH-wSP 600 mcg+saline

EXPERIMENTAL

A single injection of PATH-wSP 600 mcg in the left thigh and a single injection of saline in the right thigh along with a separate single injection of saline in the right thigh. These 3 injections are followed by a single injection of PATH-wSP 600 mcg in the left thigh 8 weeks later.

Biological: PATH-wSP; Other: Saline

Toddler Cohort 2: Active Control Only

ACTIVE COMPARATOR

A single injection of saline in the left thigh and a single injection of each of the two active comparator vaccines in the right thigh. These 3 injections are followed by a single injection of saline in the left thigh 8 weeks later.

Biological: Synflorix; Biological: Pentavac; Other: Saline

Interventions

PATH-wSP BIOLOGICAL

Streptococcus pneumoniae Whole Cell Vaccine adsorbed to Alum

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

Synflorix BIOLOGICAL

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

Also known as: 10-valent Pneumococcal Conjugate Vaccine (PCV10)

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

Pentavac BIOLOGICAL

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.

Also known as: Diptheria Pertussis Tetanus Hep B Haemophilus b Conjugate

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

Saline OTHER

0.9% Sodium Chloride Injection, USP

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

Eligibility Criteria

• Age: 12 Months - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy young Kenyan adults between 18 to 45 years of age
• Willing to provide written informed consent, able to understand comply with study requirements/procedures.
• Adult female subjects surgically sterilized or with a negative serum pregnancy test on enrollment and prior to each vaccination. Adult females must be willing to avoid becoming pregnant over the duration of the study, and must agree to employ an effective form of birth control for the duration of the study.
• Subjects willing to avoid consumption of herbal medication (including herbal medication taken by a mother, which may transmit to a toddler through breast milk) that could have effects on liver function or bleeding indices during the course of the study.
• Healthy toddlers between 12 to 15 months of age who have completed their primary EPI vaccines.
• Toddler's parent willing to provide written informed consent for subject, able to understand and comply with study requirements and procedures.
• Not premature, had a birth weight of \>2.5 kg, and a weight-to-height Z score of ≥ -2 at the time of enrollment.

You may not qualify if:

• Use of any investigational or nonregistered drug within 90 days prior and during the course of study participation.
• History of administration of any vaccine within 30 days prior to administration of study vaccine or planned vaccination during the course of study.
• History of anaphylactic shock.
• Positive test for malaria (blood film) at time of screening and when retested at Visit 1.
• Immunosuppression or immunodeficiency, inclusive of human immunodeficiency virus, by medical history or by testing at screening.
• Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, as deemed by medical history or clinical assessment.
• Evidence of active hepatitis infection (B or C) by immunologic testing at screening.
• 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 or may prevent the subject from completing the study follow-up.
• An employee (or first degree relative of employee) of the Sponsor, the Clinical Research Organization, or any investigator or site personnel.
• Any screening laboratory test result or vital sign measurement outside normal parameters and deemed by the clinician to be clinically significant, including a positive test for malaria.
• Acute illness (moderate or severe) and/or fever (tympanic temperature \>38°C for adults and \>37.5°C for toddlers), or any acute and limited illness requiring medical treatment, including the use of antibiotics and treatment for parasites.
• History of allergic disease or history of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines.
• Disorders that require chronic administration of 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; or anticipation of such administration during the study period.
• Known disturbance of coagulation or other blood disorder in adult subject or in self/first degree relative of toddler subject; or receipt of anticoagulants in the past 3 weeks.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

Kenya Medical Research Institute/Walter Reed Project

Kisumu, Nyanza, PO Box 54-40100, Kenya

Location

MeSH Terms

Conditions

Pneumonia, Pneumococcal

Interventions

PHiD-CV vaccine; 10-valent pneumococcal conjugate vaccine; Pentavac; Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumococcal Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia, Bacterial; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Jorge Flores
• Organization: PATH

jeflores@path.org

(202) 822-0033

Study Officials

• Nekoye Otsyula, MD

  Kenya Medical Research Institute/Walter Reed Project

  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: March 17, 2014
• First Posted: March 27, 2014
• Study Start: April 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: October 10, 2019
• Results First Posted: June 12, 2018

Record last verified: 2019-10

Locations

KE (1)