Clinical trial NCT03803202: A Single Ascending Dose Study in Adults (Stage 1) and Single Ascending Dose-Finding Study (Stage 2) in Elderly Subjects With ASP3772, A Pneumococcal Vaccine
Official title: A Phase 1/2, Randomized, Single Ascending Dose Study in Adults (Stage 1) and Randomized, Single Ascending Dose-Finding Study (Stage 2) in Elderly Subjects With ASP3772, a Pneumococcal Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pneumonia, Bacterial
Healthy Volunteers
Pneumococcal Disease
Keywords: Pneumococcal vaccine
Vaccine
Pneumococccal Disease
ASP3772
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Affinivax, Inc.
First posted: 2019-01-14
Enrollment: 630
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of 3 different dose levels of ASP3772 in comparison to the active comparator Prevnar 13® (PCV13) in adults 18 to 64 years of age in Stage 1. Stage 2 will evaluate the safety, tolerability, and immunogenicity of 3 different dose levels of ASP3772 in comparison to the active comparator PCV13 in elderly 65 to 85 years of age. In addition, Stage 2 will evaluate the immunogenicity of 3 different dose levels of ASP3772 relative to the response seen following administration of Pneumovax® 23 (PPSV23) for the serotypes not included in PCV13.

Detailed description: The study population will consist of 3 different groups: Group 1 - Stage 1 PCV13 naïve participants randomized within 3 sequential cohorts to ASP3772 or PCV13; Group 2 - Stage 2 PCV13 naïve participants randomized within 3 sequential cohorts to ASP3772 or PCV13; and Group 3 - Stage 2 participants previously vaccinated with PCV13 that will receive PPSV23.

Eligibility criteria: Inclusion Criteria:

* Stage 1: Subject is healthy male or female between 18 and 64 year of age inclusive, at screening.
* Stage 2: Subject is a male or female between 65 and 85 years of age, inclusive, at screening who is healthy or has chronic controlled, stable disease with no change in disease severity, medical therapy and no hospitalization records in last 12 weeks as determined by medical history, physical examination and laboratory data.
* A female subject is eligible to participate if not pregnant and at least 1 of the following conditions applies:

  * Not a woman of childbearing potential (WOCBP) OR
  * WOCBP who agrees to follow the contraceptive guidance at screening and for at least 28 days after the study vaccine administration.
* Female subject must agree not to breastfeed starting at screening and for 28 days after the study vaccine administration.
* Female subject must not donate ova starting at screening and for 28 days after the study vaccine administration.
* A male subject with female partner(s) of childbearing potential must agree to use contraception at screening and for at least 28 days after the study vaccine administration.
* Male subject must not donate sperm starting at screening and for 90 days after the study vaccine administration.
* Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding at screening and for 28 after the study vaccine administration.
* Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria:

* Subject has a known or suspected hypersensitivity to ASP3772, its comparators or any components of the formulations used.
* Subject has had previous exposure with ASP3772.
* Subject has had known previous exposure with PPSV23.
* Subject has received PCV13 or any other licensed or investigational pneumococcal vaccine at any time. (Note: This exclusion criterion is not applicable to Group 3; those subjects 65 to 85 years of age who previously received immunization with PCV13. Prior PCV13 immunization should have taken place no less than 10 months and no more than 2 years prior to study vaccine administration. These subjects are eligible to be enrolled in the nonrandomized arm of Stage 2, Group 3.
* Subject has a history of microbiologically-proven invasive disease caused by S. pneumoniae.
* Subject has an immune disorder(s) (including autoimmune disease) and/or clinical conditions requiring immunosuppressive drugs.
* Subject has any evidence of any unstable or active clinically significant cardiovascular, gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy, e.g., uncontrolled hypertension, uncontrolled diabetes, heart failure, uncontrolled chronic obstructive pulmonary disease, end-stage renal disease.
* Subject has history of illicit drug(s) or alcohol abuse that will interfere with the protocol requirements and/or a positive urine drug test (for Stage 1 subjects only) at screening.
* Subject has any clinically significant history of allergic conditions including drug allergies, asthma or anaphylactic reactions, but excluding untreated asymptomatic seasonal allergies prior to study vaccine administration.
* Subject has a coagulation disorder contraindicating intramuscular immunization.
* Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies (anti-HCV) confirmed by reflex testing (HCV-RNA) or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
* Subject has/had febrile illness (\> 100.4°F oral equivalent) or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day 1.
* Subject has any clinically significant abnormality from the physical examination, ECG and clinical laboratory tests during screening.
* Subject is unlikely to adhere to study procedures, keep appointments, is planning to relocate during the study or cannot be adequately followed for safety according to the protocol.
* Subject has any other condition, which precludes the subject's participation in the study.
* Subject has received any vaccines within 30 days prior of receipt of the study vaccine (exception: Influenza virus vaccine given according to recommended guidelines must be given at least 7 days prior to receiving study vaccine).
* Subject has had significant blood loss, donated 1 unit (450 mL or more) or received transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to day 1.
* Subject has received any systemically absorbed antibiotics during the 7-day period prior to day 1.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), [Stage 1, Group 1]
timeFrame: From Day 1, Up to Day 180
measure: Number of Participants With TEAEs, [Stage 2, Group 2]
timeFrame: From Day 1, Up to Day 180
measure: Number of Participants With TEAEs, [Stage 2, Group 3]
timeFrame: From Day 1, Up to Day 30
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs
timeFrame: During first hour post vaccination (vaccine administered at Day 1)
measure: Number of Participants With Potentially Clinically Significant Laboratory Values
timeFrame: Up to Day 30
measure: Number of Participants With Potentially Clinically Significant Physical Examination Values
timeFrame: Up to Day 30
measure: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG), [Stage 1, Group 1] and [Stage 2, Group 2]
timeFrame: Day - 28 to Day -1 (28 days prior to study vaccination)
measure: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG), [Stage 1, Group 1] and [Stage 2, Group 2]
timeFrame: At Day 7
measure: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG), [Stage 2, Group 3]
timeFrame: Day - 28 to Day -1 (28 days prior to study vaccination)
measure: Reactogenicity Assessed by Number of Participants With Solicited Local Reactions, [Stage 1, Group 1]
timeFrame: Up to 7 Day post Vaccination (vaccine administered at Day 1)
measure: Reactogenicity Assessed by Number of Solicited Local Reactions, [Stage 2, Group 2 and Group 3]
timeFrame: Up to 7 Day post Vaccination (vaccine administered at Day 1)
measure: Reactogenicity Assessed by Number of Solicited Systemic Reactions, [Stage 1, Group 1]
timeFrame: Up to 7 Day post Vaccination (vaccine administered at Day 1)
measure: Reactogenicity Assessed by Number of Solicited Systemic Reactions [Stage 2, Group 2 and Group 3]
timeFrame: Up to 7 Day post Vaccination (vaccine administered at Day 1)
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) for Serotype-specific Opsonophagocytic Activity (OPA) Titer, [Stage 1, Group 1]
timeFrame: At Day 1 and Day 30
measure: Geometric Mean Concentration (GMCs) for Serotype-specific Immunoglobulin G (IgG), [Stage 1, Group 1]
timeFrame: At Day 1 and Day 30
measure: Geometric Mean Fold Rise (GMFR) for Unique Serotypes IgG [Stage 1, Group 1]
timeFrame: At Day 30
measure: Percentage of Participants With Unique Serotypes IgG of Greater Than or Equal to (>=) 4-fold Increase, [Stage 1, Group 1]
timeFrame: At Day 30
measure: GMTs for Unique Serotype OPA Titer, [Stage 1, Group 1]
timeFrame: At Day 30
measure: GMTs for Serotype-specific OPA Titer, [Stage 2, Group 2]
timeFrame: At Day 1 and Day 30
measure: GMCs for Serotype-specific IgG, [Stage 2, Group 2]
timeFrame: At Day 1 and Day 30
measure: GMFR for Unique Serotypes IgG, [Stage 2, Group 2]
timeFrame: At Day 30
measure: Percentage of Participants With Unique Serotype-specific IgG Concentration of Greater Than or Equal to (>=) 4-fold Increase, [Stage 2, Group 2]
timeFrame: At Day 30
measure: Dose Response in OPA Titer for ASP3772 (Stage 2, Group 2)
timeFrame: At Day 30
measure: Dose Response in the IgG Concentrations for ASP3772 [Stage 2, Group 2]
timeFrame: At Day 30
measure: GMTs for Unique Serotype OPA Titer [Stage 2, Group 2 and Group 3]
timeFrame: At Day 30
measure: GMCs for Unique Serotypes IgG, [Stage 2, Group 2 and Group 3]
timeFrame: At Day 30
Other outcomes:
Locations:
city: Banning
country: United States
facility: Advanced Clinical Research-Rancho Paseo
state: California
city: San Diego
country: United States
facility: Artemis Institute
state: California
city: San Marcos
country: United States
facility: Artemis Institute
state: California
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research
state: Georgia
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Norfolk
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Binghamton
country: United States
facility: United Medical Associates
state: New York
city: Raleigh
country: United States
facility: PMG Research of Raleigh
state: North Carolina
city: Rocky Mount
country: United States
facility: PMG Research of Hickory, LLC
state: North Carolina
city: Statesville
country: United States
facility: Piedmont HealthCare, PA
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Health
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem, LLC
state: North Carolina
city: Yukon
country: United States
facility: Tekton Research - George Town
state: Oklahoma
city: Knoxville
country: United States
facility: PMG Research
state: Tennessee
city: Knoxville
country: United States
facility: PMG Research
state: Tennessee
city: Cedar Park
country: United States
facility: Advanced Clinical Research Institute
state: Texas
city: Fort Worth
country: United States
facility: Texas Healthcare, PLLC
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development
state: Texas
city: McKinney
country: United States
facility: Healthcare Associatiates of Texas
state: Texas
city: Pearland
country: United States
facility: DM Clinical Research
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic
state: Texas
city: Norfolk
country: United States
facility: CRA of Tidewater Inc
state: Virginia
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Chichili GR, Smulders R, Santos V, Cywin B, Kovanda L, Van Sant C, Malinoski F, Sebastian S, Siber G, Malley R. Phase 1/2 study of a novel 24-valent pneumococcal vaccine in healthy adults aged 18 to 64 years and in older adults aged 65 to 85 years. Vaccine. 2022 Jul 29;40(31):4190-4198. doi: 10.1016/j.vaccine.2022.05.079. Epub 2022 Jun 9.