Safety, Tolerability, and Immunogenicity of V114 in Healt... | NCT03848065

ID	Type	Description	Link
194669	Registry Identifier	JAPIC-CTI

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
V114-SC	Experimental	Infant participants will receive a single 0.5 mL subcutaneous (SC) injection of V114 on Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age). Infant participants will receive a single 0.5 mL SC injection of concomitant study vaccine [Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV) at the same time as V114-SC.](streamdown:incomplete-link)	Biological: V114 Biological: Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV)
V114-IM	Experimental	Infant participants will receive a single 0.5 mL intramuscular (IM) injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age). Infant participants will receive a single 0.5 mL SC injection of concomitant study vaccine (DTaP-IPV) at the same time as V114-IM.	Biological: V114 Biological: Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV)
PCV13-SC	Active Comparator	Infant participants will receive a single 0.5 mL subcutaneous (SC) injection of pneumococcal 13-valent conjugate vaccine (PCV13) at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age). Infant participants will receive a single 0.5 mL SC injection of concomitant study vaccine (DTaP-IPV) at the same time as PCV13-SC.	Biological: Pneumococcal 13-valent Conjugate Vaccine (PCV13) Biological: Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
V114	Biological	15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With a Solicited Injection-site Adverse Event (AE)	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs were injection site erythema (redness), injection site induration (hard lump), injection site pain and injection site swelling.	Day 1 to Day 14 post each vaccination
Percentage of Participants With a Solicited Systemic Adverse Event	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs were decreased appetite (appetite loss), somnolence (drowsiness), irritability and urticaria (hives/welts).	Day 1 to Day 14 post each vaccination
Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE)	An SAE is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator.	Up to 4 weeks post vaccination 4 (~14.5 months)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Meeting the Serotype-specific Immunoglobulin G (IgG) Threshold of ≥0.35 µg/mL	Serotype-specific pneumococcal IgG antibody was measured using pneumococcal electrochemiluminescence (PnECL). The percentage of participants with serotype-specific IgG ≥0.35 µg/mL was summarized for each serotype.	One month post vaccination 3 (~3 months after Vaccination 1)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy (based on a review of medical history and physical examination) based on the clinical judgment of the investigator.
Male or female 3 months of age inclusive (3 months of age to1 day prior to 4 months of age), at the time of obtaining the informed consent.
Has a legally acceptable representative who understands the study procedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent.

Exclusion Criteria:

Has a history of invasive pneumococcal disease (positive blood culture, positive cerebrospinal fluid culture, or other sterile site) or known history of other culture positive pneumococcal disease.
Has a known hypersensitivity to vaccines, any component of the pneumococcal conjugate vaccine or any diphtheria toxoid-containing vaccine
Has any contraindication to the PCV13 and/or diphtheria, tetanus, acellular pertussis, inactivated polio vaccine (DTaP-IPV) being administered in the study (Refer to approved labeling for contraindication details on PCV13 and DTaPIPV vaccine).
Has a recent febrile illness (axillary temperature ≥37.5°C) occurring within 72 hours prior to receipt of study vaccine.
Has a known or suspected impairment of immunological function.
Has a history of congenital or acquired immunodeficiency.
Has or his/her mother has a documented hepatitis B surface antigen - positive test.
Has a known functional or anatomic asplenia.
Has failure to thrive based on the clinical judgement of the investigator.
Has thrombocytopenia or a known coagulation disorder contraindicating intramuscular vaccination.
Has a history of autoimmune disease (including but not limited to systemic lupus erythematosus, antiphospholipid syndrome, Bechet's disease, autoimmune thyroid disease, polymyositis and dermatomyositis, scleroderma, type 1 diabetes mellitus, or other autoimmune disorders).
Has a known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders.
Has received a dose of any pneumococcal and/or DTaP-IPV vaccine (or vaccine containing any DTaP-IPV component) prior to study entry.
Meets one or more of the following systemic corticosteroid exclusion criteria: has received systemic corticosteroids (equivalent of ≥ 2 mg/kg total daily dose of prednisone or ≥ 20 mg/d for persons weighing > 10 kg) for ≥ 14 consecutive days and has not completed this course of treatment at least 30 days prior to trial randomization, has received systemic corticosteroids within 14 days prior to the first dose of study vaccine at randomization, and is expected to require systemic corticosteroids (equivalent of ≥ 2 mg/kg total daily dose of prednisone or ≥ 20 mg/d for persons weighing > 10 kg) for ≥ 14 consecutive days within 14 days prior to or 30 days after each vaccination during conduct of the study.(Topical, ophthalmic and inhaled steroids are permitted.)
Has received other licensed non-live vaccines within the 14 days before receipt of first dose of study vaccine.
Has received a licensed live virus vaccine within the 28 days before receipt of first dose of study vaccine.
Has received a blood transfusion or blood products, including immunoglobulins before receipt of first dose of study vaccine.
Has participated in another clinical study of an investigational product before the beginning or anytime during the duration of the current clinical study. Participants enrolled in observational studies may be included; these will be reviewed on a case by case basis for approval by the Sponsor.
Has any other reason that, in the opinion of the investigator, may interfere with the evaluation required by the study. (Refer to the Vaccination Guideline in Japan). Reasons may include, but are not limited to, being unable to keep appointments or planning to relocate during the study.
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Meitetsu Hospital ( Site 2805)		Nagoya	Aichi-ken	451-8511	Japan
Sotobo Children's Clinic ( Site 2807)

PubMed Identifier	Type	Citation	Retractions
36882898	Result	Ishihara Y, Kuroki H, Hidaka H, Iwai K, Wan K, Shirakawa M, Sawata M. Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028). Hum Vaccin Immunother. 2023 Dec 31;19(1):2180973. doi: 10.1080/21645515.2023.2180973. Epub 2023 Mar 7.
39384037	Result

Label	URL
Merck Clinical Trials Information	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
FG001	V114-IM	Infant participants received a single 0.5 mL intramuscular (IM) injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 12, 2018

ID	Title	Description
BG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
BG001	V114-IM	Infant participants received a single 0.5 mL IM injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
BG002	PCV13-SC	Infant participants received a single 0.5 mL SC injection of PCV13 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00044 BG00145 BG00244 BG003133

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With a Solicited Injection-site Adverse Event (AE)

An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs were injection site erythema (redness), injection site induration (hard lump), injection site pain and injection site swelling.

Analysis population consisted of all randomized participants who received at least one dose of trial vaccine.

Posted

Number

Percentage of Participants

Day 1 to Day 14 post each vaccination

ID	Title	Description
OG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG001	V114-IM	Infant participants received a single 0.5 mL IM injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG002	PCV13-SC	Infant participants received a single 0.5 mL SC injection of PCV13 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).

Units	Counts
Participants	OG00044 OG00145 OG00243

Title

Denominators

Categories

Injection Site Erythema (Redness)

Title	Measurements
	OG000100.0 OG00182.2 OG00295.3

Injection Site Induration (Hard Lump)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Injection Site Erythema (Redness)	Miettinen & Nurminen method		0.004		Difference in Percentages	17.8			2-Sided	95	9.0	31.4			Difference = % V114-SC minus % V114-IM		Other
OG000 OG002	Injection Site Erythema (Redness)

Primary

Percentage of Participants With a Solicited Systemic Adverse Event

An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs were decreased appetite (appetite loss), somnolence (drowsiness), irritability and urticaria (hives/welts).

Analysis population consisted of all randomized participants who received at least one dose of trial vaccine.

Posted

Number

Percentage of Participants

Day 1 to Day 14 post each vaccination

ID	Title	Description
OG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG001	V114-IM	Infant participants received a single 0.5 mL IM injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG002	PCV13-SC	Infant participants received a single 0.5 mL SC injection of PCV13 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).

Primary

Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE)

An SAE is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator.

Analysis population consisted of all randomized participants who received at least one dose of trial vaccine.

Posted

Number

Percentage of Participants

Up to 4 weeks post vaccination 4 (~14.5 months)

ID	Title	Description
OG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG001	V114-IM	Infant participants received a single 0.5 mL IM injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG002	PCV13-SC	Infant participants received a single 0.5 mL SC injection of PCV13 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).

Secondary

Percentage of Participants Meeting the Serotype-specific Immunoglobulin G (IgG) Threshold of ≥0.35 µg/mL

Serotype-specific pneumococcal IgG antibody was measured using pneumococcal electrochemiluminescence (PnECL). The percentage of participants with serotype-specific IgG ≥0.35 µg/mL was summarized for each serotype.

Analysis population consisted of those participants who were not considered protocol violators.

Posted

Number

Percentage of Participants

One month post vaccination 3 (~3 months after Vaccination 1)

ID	Title	Description
OG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG001	V114-IM	Infant participants received a single 0.5 mL IM injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG002	PCV13-SC	Infant participants received a single 0.5 mL SC injection of PCV13 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).

Secondary

Serotype-specific IgG Geometric Mean Concentrations (GMCs)

The anti-pneumococcal polysaccharide (PnPs) serotype-specific IgG Geometric Mean Concentrations (GMCs) were determined using an electrochemiluminescence assay.

Analysis population consisted of those participants who were not considered protocol violators.

Posted

Geometric Mean

95% Confidence Interval

μg/mL

1 month post vaccination 3 (~3 months after Vaccination 1)

ID	Title	Description
OG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG001	V114-IM	Infant participants received a single 0.5 mL IM injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG002	PCV13-SC	Infant participants received a single 0.5 mL SC injection of PCV13 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).

Units

Secondary

Percentage of Participants Meeting Threshold Values for Protective Responses to DTaP-IPV (Diphtheria Toxin, Tetanus Toxin, Pertussis Toxin, Pertussis Filamentous Hemagglutinin (FHA) and Polio Virus Type 1/2/3)

DTaP-IPV antibody titers were measured by neutralization assay (diphtheria toxin and poliovirus 1/2/3), particle agglutination assay (tetanus toxin) and enzyme-linked immunosorbent assay (ELISA) methodology (pertussis PT and pertussis FHA) 1 month post vaccination 3. Threshold values were: Diphtheria toxin level ≥0.1 IU/mL, Pertussis PT level ≥10 EU/mL, Pertussis FHA level ≥10 EU/mL, Tetanus toxin level ≥0.01 IU/mL, Neutralizing antibody (NA) titers of Polio virus types 1/2/3 ≥1:8.

Analysis population consisted of those participants who were not considered protocol violators.

Posted

Number

Percentage of Participants

1 month post vaccination 3 (~3 months after Vaccination 1)

ID	Title	Description
OG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG001	V114-IM	Infant participants received a single 0.5 mL IM injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).
OG002	PCV13-SC

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0006 events1 affected44 at risk EG0010 events0 affected45 at risk EG0023 events3 affected43 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0004 events4 affected44 at risk EG0018 events5 affected45 at risk EG0026 events6 affected43 at risk
Injection site erythema	General disorders	MedDRA 23.1	Systematic Assessment	EG000236 events44 affected44 at risk EG001145 events37 affected45 at risk EG002217 events41 affected43 at risk
Injection site induration	General disorders	MedDRA 23.1	Systematic Assessment	EG000215 events40 affected44 at risk EG001144 events35 affected45 at risk EG002229 events43 affected43 at risk
Injection site pain	General disorders	MedDRA 23.1	Systematic Assessment	EG00043 events17 affected44 at risk EG00130 events13 affected45 at risk EG00249 events18 affected43 at risk
Injection site swelling	General disorders	MedDRA 23.1	Systematic Assessment	EG000174 events38 affected44 at risk EG00187 events33 affected45 at risk EG002163 events38 affected43 at risk
Injection site warmth	General disorders	MedDRA 23.1	Systematic Assessment	EG00010 events3 affected44 at risk EG0014 events2 affected45 at risk EG00210 events6 affected43 at risk
Pyrexia	General disorders	MedDRA 23.1	Systematic Assessment	EG00063 events27 affected44 at risk EG00150 events25 affected45 at risk EG00253 events27 affected43 at risk
Nasopharyngitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0005 events5 affected44 at risk EG0013 events3 affected45 at risk EG0023 events3 affected43 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG00019 events11 affected44 at risk EG00130 events16 affected45 at risk EG00232 events15 affected43 at risk
Somnolence	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG00064 events31 affected44 at risk EG00175 events27 affected45 at risk EG00281 events32 affected43 at risk
Irritability	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG00090 events36 affected44 at risk EG00187 events32 affected45 at risk EG002102 events32 affected43 at risk
Upper respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0009 events7 affected44 at risk EG0018 events8 affected45 at risk EG00211 events9 affected43 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected44 at risk EG0010 events0 affected45 at risk EG0023 events3 affected43 at risk
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0005 events4 affected44 at risk EG0012 events2 affected45 at risk EG0025 events5 affected43 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0007 events6 affected44 at risk EG0011 events1 affected45 at risk EG0021 events1 affected43 at risk
Eczema infantile	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected44 at risk EG0013 events3 affected45 at risk EG0022 events2 affected43 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected44 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Miliaria	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0004 events3 affected44 at risk EG0011 events1 affected45 at risk EG0022 events2 affected43 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected44 at risk EG0013 events3 affected45 at risk EG0023 events3 affected43 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 23.1	Systematic Assessment	EG0005 events4 affected44 at risk EG0013 events2 affected45 at risk EG0025 events3 affected43 at risk

ID	Term
D013290	Streptococcal Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

ID	Term
C538862	13-valent pneumococcal vaccine
D017778	Vaccines, Combined

ID	Term
D014612	Vaccines
D001688	Biological Products
D045424	Complex Mixtures

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	V114-SC	Infant participants received a single 0.5 mL SC injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).	0	44	1	44	44	44
EG001	V114-IM	Infant participants received a single 0.5 mL IM injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).	1	45	3	45	44	45
EG002	PCV13-SC	Infant participants received a single 0.5 mL SC injection of PCV13 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).	0	44	2	43	43	43

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardio-respiratory arrest	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected44 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Hand-foot-and-mouth disease	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected44 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Pneumonia respiratory syncytial viral	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected44 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected44 at risk EG0011 events1 affected45 at risk EG0021 events1 affected43 at risk