A Study of a Vaccine for Pneumonia in Adults and Toddlers in Kenya

NCT02543892 | Completed Phase 1 Results DMC

• 1 other identifier: VAC-040
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to determine whether PATH-wSP, a vaccine against a germ that causes pneumonia, is safe and induces immune responses in adults and toddlers. The study vaccine was compared to placebo. First adults received 2 injections of a lower dose of the vaccine or placebo, 28 days apart. Since the lower dose was considered safe, a higher dose was tested. Once the safety was established in adults the lower and higher dose was tested in toddlers, starting with the lower dose and then the higher dose.

Conditions

Pneumonia

Keywords

Vaccine

Outcome Measures

Primary Outcomes (5)

• 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.

  7 days after the first dose (Day 7)

• Highest Grade of Reactogenicity Events in the Toddler 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, 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.

  7 days after the second dose (Day 35)

• Number of Adverse Events (AE), by Relation to Vaccine and Seriousness

  Only treatment-emergent adverse events (TEAEs) were included in the analysis; adverse events (AEs) that were not TEAEs were to have been listed.

  112 days

Secondary Outcomes (3)

• Immunoglobulin G (IgG) Antibody Geometric Mean Concentration Against Pneumococcal Proteins

  Baseline and 12 weeks after vaccination 2 (Day 0 and Day 112)

• Immunoglobulin G (IgG) Antibody Geometric Mean Fold Change Against Pneumococcal Proteins

  Baseline and 12 weeks after vaccination 2 (Day 0 and Day 112)

• Number of Subjects With Immunoglobulin G (IgG) Seroresponse

  Baseline and 12 weeks after vaccination 2 (Day 0 and Day 112)

Study Arms (8)

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

Biological: Placebo

Toddler 1.0 mg PATH-wSP

EXPERIMENTAL

Two 1 mg doses of PATH-wSP with a 28 day interval between doses

Biological: PATH-wSP

Toddler Placebo High Dose

PLACEBO COMPARATOR

Two injections of normal saline with a 28 day interval between injections

Biological: Placebo

Interventions

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; Toddler 0.6mg PATH-wSP; Toddler 1.0 mg PATH-wSP

Placebo BIOLOGICAL

Normal Saline

Adult Placebo High Dose; Adult Placebo Low Dose; Toddler Placebo High Dose; Toddler Placebo Low Dose

Eligibility Criteria

• Age: 1 Year - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

KEMRI-Wellcome Trust Research Programme; Centre for Geographic Medicine Research - Coast

Kilifi, 80108, Kenya

Location

MeSH Terms

Conditions

Pneumonia

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Jorge Flores
• Organization: PATH

jeflores@path.org

(202) 822-0033

Study Officials

• Anthony Scott, MD

  London School of Hygiene and Tropical Medicine

  STUDY CHAIR

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: September 1, 2015
• First Posted: September 7, 2015
• Study Start: August 10, 2016
• Primary Completion: January 4, 2018
• Study Completion: January 4, 2018
• Last Updated: November 28, 2018
• Results First Posted: November 28, 2018

Record last verified: 2018-11

Locations

KE (1)