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

NCT03803202 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2196593772-CL-1001
• Study Type: interventional
• Target: 630
• Locations: 1 country
• Sites: 26

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.

Conditions

Pneumonia, Bacterial; Healthy Volunteers; Pneumococcal Disease

Keywords

Pneumococcal vaccine; Vaccine; Pneumococccal Disease; ASP3772

Outcome Measures

Primary Outcomes (13)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), [Stage 1, Group 1]

  An AE is any untoward medical occurrence in a participant administered a study vaccine, and which does not necessarily have to have a causal relationship with this vaccination. A TEAE is defined as any AE with onset within 30 days from study vaccine administration. Medically attended TEAEs (MAAEs) are AEs for which the participant has received medical attention by medical personnel, or in an emergency room, or which led to hospitalization. A new-onset chronic disease TEAEs (NOCD) is defined as a MAAE which a) was absent at baseline; b) has not resolved at the follow-up telephone call; c) requires continuous medical care or attention. Potentially Immune Mediated medical condition TEAEs (PIMMCs) are defined as any AEs of autoimmune or auto inflammatory nature.

  From Day 1, Up to Day 180

• Number of Participants With TEAEs, [Stage 2, Group 2]

  An AE is any untoward medical occurrence in a participant administered a study vaccine, and which does not necessarily have to have a causal relationship with this vaccination. A TEAE is defined as any AE with onset within 30 days from study vaccine administration. Medically attended TEAEs (MAAEs) are AEs for which the participant has received medical attention by medical personnel, or in an emergency room, or which led to hospitalization. A new-onset chronic disease TEAEs (NOCD) is defined as a MAAE which a) was absent at baseline; b) has not resolved at the follow-up telephone call; c) requires continuous medical care or attention. Potentially Immune Mediated medical condition TEAEs (PIMMCs) are defined as any AEs of autoimmune or auto inflammatory nature. As specified in protocol, data was planned to be analyzed for PCV13 pooled comparator from each group given PCV13 to compare with each ASP3772 dose.

  From Day 1, Up to Day 180

• Number of Participants With TEAEs, [Stage 2, Group 3]

  An AE is any untoward medical occurrence in a participant administered a study vaccine, and which does not necessarily have to have a causal relationship with this vaccination. A TEAE is defined as any AE with onset within 30 days from study vaccine administration. Medically attended TEAEs (MAAEs) are AEs for which the participant has received medical attention by medical personnel, or in an emergency room, or which led to hospitalization. A new-onset chronic disease TEAEs (NOCD) is defined as a MAAE which a) was absent at baseline; b) has not resolved at the follow-up telephone call; c) requires continuous medical care or attention. Potentially Immune Mediated medical condition TEAEs (PIMMCs) are defined as any AEs of autoimmune or auto inflammatory nature.

  From Day 1, Up to Day 30

• Number of Participants With Clinically Significant Abnormalities in Vital Signs

  Vital signs parameters included blood pressure (hypotension and hypertension), pulse rate (tachycardia and bradycardia), body temperature and respiratory rate. Any change in vital sign abnormalities that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.

  During first hour post vaccination (vaccine administered at Day 1)

• Number of Participants With Potentially Clinically Significant Laboratory Values

  Clinical laboratory testing included hematology, clinical chemistry, or urinalysis. Any abnormal laboratory test result (e.g., in hematology, clinical chemistry, or urinalysis) that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Laboratory tests of clinical interest included total bilirubin ≥ 2x ULN and Alkaline phosphatase \> 1.5 × upper limit of normal. Study Investigator's interest was to assess only potentially clinically significant values.

  Up to Day 30

• Number of Participants With Potentially Clinically Significant Physical Examination Values

  A physical examination consists of an examination of general appearance, eyes, nose throat, neck (including thyroid), lymph nodes, chest, lungs, cardiovascular, abdomen, skin, extremities, musculoskeletal and neurological system including mental status. Any abnormal test result that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Study Investigator's interest was to assess only potentially clinically significant values.

  Up to Day 30

• Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG), [Stage 1, Group 1] and [Stage 2, Group 2]

  The Investigator assessed standard 12-lead ECG recordings for the purposes of safety assessment and participant management. Any clinically significant abnormality, as determined by the investigator's medical and scientific judgment and unrelated to underlying disease, should be reported as an unsolicited (S)AE. Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.

  Day - 28 to Day -1 (28 days prior to study vaccination)

• Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG), [Stage 1, Group 1] and [Stage 2, Group 2]

  The Investigator assessed standard 12-lead ECG recordings for the purposes of safety assessment and participant management. Any clinically significant abnormality, as determined by the investigator's medical and scientific judgment and unrelated to underlying disease, should be reported as an unsolicited (S)AE. Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.

  At Day 7

• Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG), [Stage 2, Group 3]

  The Investigator assessed standard 12-lead ECG recordings for the purposes of safety assessment and participant management. Any clinically significant abnormality, as determined by the investigator's medical and scientific judgment and unrelated to underlying disease, should be reported as an unsolicited (S)AE. Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.

  Day - 28 to Day -1 (28 days prior to study vaccination)

• Reactogenicity Assessed by Number of Participants With Solicited Local Reactions, [Stage 1, Group 1]

  Local reactions include pain, tenderness, redness/erythema, swelling and induration.

  Up to 7 Day post Vaccination (vaccine administered at Day 1)

• Reactogenicity Assessed by Number of Solicited Local Reactions, [Stage 2, Group 2 and Group 3]

  Assessed solicited local reactions were pain, tenderness, redness/erythema, swelling, induration, itching at injection site and pruritus at injection site.

  Up to 7 Day post Vaccination (vaccine administered at Day 1)

• Reactogenicity Assessed by Number of Solicited Systemic Reactions, [Stage 1, Group 1]

  Assessed systemic reactions were nausea/vomiting, diarrhea, headache, fever, fatigue and muscle discomfort or pain/myalgia.

  Up to 7 Day post Vaccination (vaccine administered at Day 1)

• Reactogenicity Assessed by Number of Solicited Systemic Reactions [Stage 2, Group 2 and Group 3]

  Assessed systemic reactions were nausea/vomiting, diarrhea, headache, fever, fatigue and muscle discomfort or pain/myalgia.

  Up to 7 Day post Vaccination (vaccine administered at Day 1)

Secondary Outcomes (13)

• Geometric Mean Titers (GMTs) for Serotype-specific Opsonophagocytic Activity (OPA) Titer, [Stage 1, Group 1]

  At Day 1 and Day 30

• Geometric Mean Concentration (GMCs) for Serotype-specific Immunoglobulin G (IgG), [Stage 1, Group 1]

  At Day 1 and Day 30

• Geometric Mean Fold Rise (GMFR) for Unique Serotypes IgG [Stage 1, Group 1]

  At Day 30

• Percentage of Participants With Unique Serotypes IgG of Greater Than or Equal to (>=) 4-fold Increase, [Stage 1, Group 1]

  At Day 30

• GMTs for Unique Serotype OPA Titer, [Stage 1, Group 1]

  At Day 30

Study Arms (9)

Stage 1, Group 1 Adults, ASP3772 Low dose

EXPERIMENTAL

Healthy adults aged 18 to 64 years received a low dose \[1 microgram (μg)\] of ASP3772 intramuscularly on Day 1.

Biological: ASP3772

Stage 1, Group 1 Adults, ASP3772 Medium dose

EXPERIMENTAL

Healthy adults aged 18 to 64 years received a medium dose (2 μg) of ASP3772 intramuscularly on Day 1.

Biological: ASP3772

Stage 1, Group 1 Adults, ASP3772 High dose

EXPERIMENTAL

Healthy adults aged 18 to 64 years received a high dose (5 μg) of ASP3772 intramuscularly on Day 1.

Biological: ASP3772

Stage 1, Group 1, PCV13 Pooled Comparator

ACTIVE COMPARATOR

Healthy adults aged 18 to 64 years received a single dose of PCV13 0.5 milliliter (mL) intramuscularly on Day 1. Data from participants in each group given PCV13 were pooled for comparison with each ASP3772 dose group (ASP3772 low dose, ASP3772 medium dose and ASP3772 high dose).

Biological: PCV13

Stage 2, Group 2 Older Adults, ASP3772 Low dose

EXPERIMENTAL

Healthy older adults aged 65 to 85 years received a low dose (1 μg) of ASP3772 intramuscularly on Day 1.

Biological: ASP3772

Stage 2, Group 2 Older Adults, ASP3772 Medium dose

EXPERIMENTAL

Healthy older adults aged 65 to 85 years received a medium dose (2 μg) of ASP3772 intramuscularly on Day 1.

Biological: ASP3772

Stage 2, Group 2 Older Adults, ASP3772 High dose

EXPERIMENTAL

Healthy older adults aged 65 to 85 years received a high dose (5 μg) of ASP3772 intramuscularly on Day 1.

Biological: ASP3772

Stage 2, Group 2, PCV13 Pooled Comparator

ACTIVE COMPARATOR

Older adults aged 65 to 85 years received a single dose of PCV13 0.5 mL intramuscularly on Day 1. Data from participants in each group given PCV13 were pooled for comparison with each ASP3772 dose group (ASP3772 low dose, ASP3772 medium dose and ASP3772 high dose).

Biological: PCV13

Stage 2, Group 3, PPSV23 Comparator

ACTIVE COMPARATOR

Older adults aged 65 to 85 years who had been previously vaccinated with PCV13, were enrolled and received a single of dose PPSV23 on Day 1.

Biological: PPSV23

Interventions

ASP3772 BIOLOGICAL

Participants received a single dose of ASP3772 (ASP3772 low dose, ASP3772 medium dose and ASP3772 high dose) intramuscularly

Stage 1, Group 1 Adults, ASP3772 High dose; Stage 1, Group 1 Adults, ASP3772 Low dose; Stage 1, Group 1 Adults, ASP3772 Medium dose; Stage 2, Group 2 Older Adults, ASP3772 High dose; Stage 2, Group 2 Older Adults, ASP3772 Low dose; Stage 2, Group 2 Older Adults, ASP3772 Medium dose

PCV13 BIOLOGICAL

Participants received a single dose of PCV13 intramuscularly.

Also known as: Prevnar 13

Stage 1, Group 1, PCV13 Pooled Comparator; Stage 2, Group 2, PCV13 Pooled Comparator

PPSV23 BIOLOGICAL

Participants received a single dose of PPSV23 intramuscularly.

Also known as: Pneumovax 23

Stage 2, Group 3, PPSV23 Comparator

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Affinivax, Inc.: collaborator

Study Sites (26)

Advanced Clinical Research-Rancho Paseo

Banning, California, 92220, United States

Location

Artemis Institute

San Diego, California, 92103, United States

Location

Artemis Institute

San Marcos, California, 92078, United States

Location

Research Centers of America

Hollywood, Florida, 33024, United States

Location

Meridian Clinical Research

Savannah, Georgia, 31406, United States

Location

Sundance Clinical Research

St Louis, Missouri, 63141, United States

Location

Meridian Clinical Research

Norfolk, Nebraska, 68701, United States

Location

United Medical Associates

Binghamton, New York, 13901, United States

Location

PMG Research of Raleigh

Raleigh, North Carolina, 27604, United States

Location

PMG Research of Hickory, LLC

Rocky Mount, North Carolina, 27804, United States

Location

Piedmont HealthCare, PA

Statesville, North Carolina, 28625, United States

Location

Wilmington Health

Wilmington, North Carolina, 28401, United States

Location

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Tekton Research - George Town

Yukon, Oklahoma, 73099, United States

Location

PMG Research

Knoxville, Tennessee, 37912, United States

Location

PMG Research

Knoxville, Tennessee, 37938, United States

Location

Advanced Clinical Research Institute

Cedar Park, Texas, 78613, United States

Location

Texas Healthcare, PLLC

Fort Worth, Texas, 76104, United States

Location

Benchmark Research

Fort Worth, Texas, 76135, United States

Location

Texas Center for Drug Development

Houston, Texas, 77081, United States

Location

Healthcare Associatiates of Texas

McKinney, Texas, 75070, United States

Location

DM Clinical Research

Pearland, Texas, 77584, United States

Location

Benchmark Research

San Angelo, Texas, 76904, United States

Location

Clinical Trials of Texas

San Antonio, Texas, 78229, United States

Location

Martin Diagnostic Clinic

Tomball, Texas, 77375, United States

Location

CRA of Tidewater Inc

Norfolk, Virginia, 23507, United States

Location

Related Publications (2)

• Borys D, Rupp R, Smulders R, Chichili GR, Kovanda LL, Santos V, Malinoski F, Siber G, Malley R, Sebastian S. Safety, tolerability and immunogenicity of a novel 24-valent pneumococcal vaccine in toddlers: A phase 1 randomized controlled trial. Vaccine. 2024 Apr 11;42(10):2560-2571. doi: 10.1016/j.vaccine.2024.02.001. Epub 2024 Feb 14.

  PMID: 38360475 DERIVED

• 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.

  PMID: 35690500 DERIVED

MeSH Terms

Conditions

Pneumonia, Bacterial; Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine; 23-valent pneumococcal capsular polysaccharide vaccine

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: January 14, 2019
• Study Start: January 24, 2019
• Primary Completion: September 28, 2020
• Study Completion: September 28, 2020
• Last Updated: December 21, 2023
• Results First Posted: December 21, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

US (26)