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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03803202
• Other study ID #: 219659
• Secondary ID: 3772-CL-1001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 24, 2019
• Est. completion date: September 28, 2020

Study information

• Verified date: November 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 630
• Est. completion date: September 28, 2020
• Est. primary completion date: September 28, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers
• Pneumococcal Disease
• Pneumococcal Infections
• Pneumonia, Bacterial

Intervention

Biological:
• ASP3772
Participants received a single dose of ASP3772 (ASP3772 low dose, ASP3772 medium dose and ASP3772 high dose) intramuscularly
• PCV13
Participants received a single dose of PCV13 intramuscularly.
• PPSV23
Participants received a single dose of PPSV23 intramuscularly.

Locations

Country	Name	City	State
United States	Advanced Clinical Research-Rancho Paseo	Banning	California
United States	United Medical Associates	Binghamton	New York
United States	Advanced Clinical Research Institute	Cedar Park	Texas
United States	Benchmark Research	Fort Worth	Texas
United States	Texas Healthcare, PLLC	Fort Worth	Texas
United States	Research Centers of America	Hollywood	Florida
United States	Texas Center for Drug Development	Houston	Texas
United States	PMG Research	Knoxville	Tennessee
United States	PMG Research	Knoxville	Tennessee
United States	Healthcare Associatiates of Texas	McKinney	Texas
United States	CRA of Tidewater Inc	Norfolk	Virginia
United States	Meridian Clinical Research	Norfolk	Nebraska
United States	DM Clinical Research	Pearland	Texas
United States	PMG Research of Raleigh	Raleigh	North Carolina
United States	PMG Research of Hickory, LLC	Rocky Mount	North Carolina
United States	Sundance Clinical Research	Saint Louis	Missouri
United States	Benchmark Research	San Angelo	Texas
United States	Clinical Trials of Texas	San Antonio	Texas
United States	Artemis Institute	San Diego	California
United States	Artemis Institute	San Marcos	California
United States	Meridian Clinical Research	Savannah	Georgia
United States	Piedmont HealthCare, PA	Statesville	North Carolina
United States	Martin Diagnostic Clinic	Tomball	Texas
United States	Wilmington Health	Wilmington	North Carolina
United States	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina
United States	Tekton Research - George Town	Yukon	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Affinivax, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	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
Primary	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
Primary	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)
Primary	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
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Geometric Mean Titers (GMTs) for Serotype-specific Opsonophagocytic Activity (OPA) Titer, [Stage 1, Group 1]	OPA titers were determined for serotypes: 1, 3,4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F. OPA titer was expressed as the reciprocal of the serum dilution that causes a 50% reduction in the colony-forming units.	At Day 1 and Day 30
Secondary	Geometric Mean Concentration (GMCs) for Serotype-specific Immunoglobulin G (IgG), [Stage 1, Group 1]	Immunological responses were assessed in terms of IgG GMCs and expressed as titers. The assessed serotypes were: 1, 3,4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F.	At Day 1 and Day 30
Secondary	Geometric Mean Fold Rise (GMFR) for Unique Serotypes IgG [Stage 1, Group 1]	Immunological responses were assessed in terms of IgG GMFRs. The assessed serotypes were: 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F.	At Day 30
Secondary	Percentage of Participants With Unique Serotypes IgG of Greater Than or Equal to (>=) 4-fold Increase, [Stage 1, Group 1]	Immunological responses were assessed in terms of percentage of participants with serotype-specific IgG concentration >=4-fold increase. The assessed serotypes were: 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, 33F.	At Day 30
Secondary	GMTs for Unique Serotype OPA Titer, [Stage 1, Group 1]	Immunological responses were assessed in terms of OPA GMTs. The assessed serotypes were: 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, 33F.	At Day 30
Secondary	GMTs for Serotype-specific OPA Titer, [Stage 2, Group 2]	Immunological responses were assessed in terms of OPA GMTs and expressed as titers. The assessed serotypes were: 1, 3,4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F.	At Day 1 and Day 30
Secondary	GMCs for Serotype-specific IgG, [Stage 2, Group 2]	Immunological responses were assessed in terms of IgG GMCs and expressed as titers. The assessed serotypes were: 1, 3,4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F.	At Day 1 and Day 30
Secondary	GMFR for Unique Serotypes IgG, [Stage 2, Group 2]	Immunological responses were assessed in terms of IgG GMFRs. The assessed serotypes were: 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F.	At Day 30
Secondary	Percentage of Participants With Unique Serotype-specific IgG Concentration of Greater Than or Equal to (>=) 4-fold Increase, [Stage 2, Group 2]	Immunological responses were assessed in terms of percentage of participants with unique serotypes IgG concentration >=4-fold increase. The assessed serotypes were: 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, 33F.	At Day 30
Secondary	Dose Response in OPA Titer for ASP3772 (Stage 2, Group 2)	An analysis of covariance (ANCOVA) model was conducted with age categories (65 to 74 years and 75 to 85 years) serving as covariates, and treatment groups (ASP3772 1 µg, 2 µg, and 5 µg) as the factor of interest. The natural logarithm (log) of pneumococcal OPA titers for each serotype were examined to assess the dose-response relationship. The assessed serotypes were: 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F,20B, 22F, 23F, and 33F. he assessed serotypes were: 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F,20B, 22F, 23F, and 33F.	At Day 30
Secondary	Dose Response in the IgG Concentrations for ASP3772 [Stage 2, Group 2]	An analysis of covariance (ANCOVA) model was conducted with age categories (65 to 74 years and 75 to 85 years) serving as covariates, and treatment groups (ASP3772 1 µg, 2 µg, and 5 µg) as the factor of interest. The natural logarithm (log) of IgG concentrations for each serotype were examined to assess the dose-response relationship.	At Day 30
Secondary	GMTs for Unique Serotype OPA Titer [Stage 2, Group 2 and Group 3]	Immunological responses were assessed in terms of OPA GMTs. The assessed serotypes were: 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, 33F.	At Day 30
Secondary	GMCs for Unique Serotypes IgG, [Stage 2, Group 2 and Group 3]	Immunogenicity was measured in terms of IgG GMCs and expressed as titers. The assessed serotypes were: 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, 33F.	At Day 30