A Study to Evaluate the Safety, Tolerability, and Immunog... | NCT03731182

ID	Type	Description	Link
V114-023	Other Identifier	Merck Protocol Number
2018-001152-35	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
V114	Experimental	Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 on Day 1.	Biological: V114
Prevnar 13™	Active Comparator	Participants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1.	Biological: Prevnar 13™

Name	Type	Description	Arm Group Labels	Other Names
V114	Biological	V114 pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), and serotype 6B (4 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	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs included injection-site erythema (redness), injection-site induration (hard lump), injection-site pain (tenderness), and injection-site swelling.	Up to 14 days post-vaccination
Percentage of Participants With a Solicited Systemic Adverse Event	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain), and urticaria (hives or welts).	Up to 14 days post-vaccination
Percentage of Participants With a Vaccine-related Serious Adverse Event	A serious adverse event (SAE) is an AE that results in death, 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. SAEs that were reported by the investigator to be at least possibly related to the study vaccination were summarized.	Up to 6 months post-vaccination
Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) at Day 30	The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay.	Day 30

Secondary Outcomes

Measure	Description	Time Frame
Geometric Mean Titer (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) at Day 30	Sera from participants was used to measure GMT of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 using the multiplexed opsonophagocytic assay (MOPA).	Day 30

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Documented diagnosis of sickle cell disease in their medical record
Female participants: not pregnant or breastfeeding, and at least 1 of the following conditions apply:

1) not a woman of childbearing potential (WOCBP) as defined in the protocol, or 2) a WOCBP who agrees to follow the contraceptive guidance in the protocol during the treatment period and for at least 6 weeks after the last dose of study vaccine
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/assent.

Exclusion Criteria:

History of Invasive Pneumococcal Disease (positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site) or known history of other culture-positive pneumococcal disease within 3 years of Visit 1 (Day 1)
Known hypersensitivity to any component of pneumococcal conjugate vaccine (PCV), or any diphtheria toxoid-containing vaccine
Known or suspected impairment of immunological function
History of congenital or acquired immunodeficiency
Documented human immunodeficiency virus (HIV) infection
History of autoimmune disease (including but not limited to systemic lupus erythematosus, antiphospholipid syndrome, Behcet's disease, autoimmune thyroid disease, polymyositis and dermatomyositis, scleroderma, or type 1 diabetes mellitus)
Known coagulation disorder contraindicating intramuscular vaccination
History of malignancy ≤5 years prior to signing informed consent/assent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
A WOCBP who has a positive urine or serum pregnancy test before the first vaccination at Visit 1 (Day 1)
Received any PCV or pneumococcal polysaccharide vaccine <3 years before Visit 1 (Day 1)
Five (5) years of age and has received <3 doses of PCV
Receiving immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease. Note: hydroxyurea is permitted
Received immunoglobulin within 6 months before receipt of study vaccine
Participated in another clinical study of an investigational product within 2 months before the beginning or anytime during the duration of the current clinical study. Participants enrolled in observational studies may be included
Recent history (within the last year) of more than 3 inpatient hospitalizations
At the time of signing informed consent/assent, is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence as assessed by the study investigator
History or current evidence of any condition, therapy, lab abnormality or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study in the opinion of the Investigator
Is or has an immediate family member (eg, 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
Nemours/Alfred I. duPont Hospital for Children ( Site 0113)		Wilmington	Delaware	19803	United States

PubMed Identifier	Type	Citation	Retractions
36383730	Derived	Quinn CT, Wiedmann RT, Jarovsky D, Lopez-Medina E, Rodriguez HM, Papa M, Boggio G, Shou Q, Dagan R, Richmond P, Feemster K, McFetridge R, Tamms G, Lupinacci R, Musey L, Bickham K. Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in children with SCD: a V114-023 (PNEU-SICKLE) study. Blood Adv. 2023 Feb 14;7(3):414-421. doi: 10.1182/bloodadvances.2022008037.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	V114	Participants received a single 0.5 mL intramuscular (IM) injection of V114 on Day 1.
FG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

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	Sep 6, 2018

ID	Title	Description
BG000	V114	Participants received a single 0.5 mL IM injection of V114 on Day 1.
BG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00070 BG00134 BG002104

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

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

All randomized participants who received at least 1 dose of study vaccination

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 14 days post-vaccination

ID	Title	Description
OG000	V114	Participants received a single 0.5 mL IM injection of V114 on Day 1.
OG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

Units	Counts
Participants	OG00069 OG00134

Title

Denominators

Categories

Injection site erythema

Title	Measurements
	OG0004.3± 0.9(0.9 to 12.2) OG0015.9± 0.7(0.7 to 19.7)

Injection site induration

Title	Measurements
	OG000

Primary

Percentage of Participants With a Solicited Systemic Adverse Event

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain), and urticaria (hives or welts).

All randomized participants who received at least 1 dose of study vaccination

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 14 days post-vaccination

ID	Title	Description
OG000	V114	Participants received a single 0.5 mL IM injection of V114 on Day 1.
OG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

Units	Counts
Participants	OG000

Primary

Percentage of Participants With a Vaccine-related Serious Adverse Event

A serious adverse event (SAE) is an AE that results in death, 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. SAEs that were reported by the investigator to be at least possibly related to the study vaccination were summarized.

All randomized participants who received at least 1 dose of study vaccination

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 6 months post-vaccination

ID	Title	Description
OG000	V114	Participants received a single 0.5 mL IM injection of V114 on Day 1.
OG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

Units	Counts
Participants	OG000

Primary

Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) at Day 30

The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay.

All randomized participants without deviations from the protocol that may have substantially affected the results of this immunogenicity endpoint and who had sufficient data to perform the analyses

Posted

Geometric Mean

95% Confidence Interval

μg/mL

Day 30

ID	Title	Description
OG000	V114	Participants received a single 0.5 mL IM injection of V114 on Day 1.
OG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

Units	Counts
Participants	OG000

Secondary

Geometric Mean Titer (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) at Day 30

Sera from participants was used to measure GMT of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 using the multiplexed opsonophagocytic assay (MOPA).

All randomized participants without deviations from the protocol that may have substantially affected the results of this immunogenicity endpoint and who had sufficient data to perform the analyses

Posted

Geometric Mean

95% Confidence Interval

1/dil

Day 30

ID	Title	Description
OG000	V114	Participants received a single 0.5 mL IM injection of V114 on Day 1.
OG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

Units	Counts
Participants	OG000

Secondary

Geometric Mean Fold Rise (GMFR) in Serotype-specific IgG From Day 1 (Baseline) to Day 30

IgG for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes unique to V114 (22F and 33F) was determined using an electrochemiluminescence assay. GMFR is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline (Day 1, pre-vaccination).

All randomized participants without protocol deviations that could have substantially impacted the results of these immunogenicity analyses and who had sufficient data to perform the analyses

Posted

Geometric Mean

95% Confidence Interval

Ratio

Day 1 (Baseline) and Day 30

ID	Title	Description
OG000	V114	Participants received a single 0.5 mL IM injection of V114 on Day 1.
OG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

Units	Counts
Participants

Secondary

GMFR in Serotype-specific OPA From Day 1 (Baseline) to Day 30

Activity for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes unique to V114 (22F and 33F) was determined using a MOPA. GMFR is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline (Day 1, pre-vaccination).

All randomized participants without protocol deviations that could have substantially affected the results of these immunogenicity analyses and who had sufficient data to perform the analyses

Posted

Geometric Mean

95% Confidence Interval

Ratio

Day 1 (Baseline) and Day 30

ID	Title	Description
OG000	V114	Participants received a single 0.5 mL intramuscular IM injection of V114 on Day 1.
OG001	Prevnar 13™	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Sickle cell anaemia with crisis	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0009 events7 affected69 at risk EG0017 events6 affected34 at risk
Pneumonia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected69 at risk EG0011 events1 affected34 at risk
Pyelonephritis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected69 at risk EG0010 events0 affected34 at risk
Respiratory tract infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected69 at risk EG0010 events0 affected34 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected69 at risk EG0010 events0 affected34 at risk
Viral infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected69 at risk EG0011 events1 affected34 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected69 at risk EG0010 events0 affected34 at risk
Medical observation	Investigations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected69 at risk EG0010 events0 affected34 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected69 at risk EG0010 events0 affected34 at risk
Acute chest syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected69 at risk EG0010 events0 affected34 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	MedDRA 23.1	Systematic Assessment	EG0009 events9 affected69 at risk EG0017 events7 affected34 at risk
Injection site erythema	General disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected69 at risk EG0012 events2 affected34 at risk
Injection site induration	General disorders	MedDRA 23.1	Systematic Assessment	EG0006 events6 affected69 at risk EG0013 events3 affected34 at risk
Injection site pain	General disorders	MedDRA 23.1	Systematic Assessment	EG00048 events42 affected69 at risk EG00125 events23 affected34 at risk
Injection site swelling	General disorders	MedDRA 23.1	Systematic Assessment	EG00021 events19 affected69 at risk EG00114 events12 affected34 at risk
Pyrexia	General disorders	MedDRA 23.1	Systematic Assessment	EG0004 events4 affected69 at risk EG0011 events1 affected34 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0003 events2 affected69 at risk EG0014 events3 affected34 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0004 events4 affected69 at risk EG0011 events1 affected34 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG00020 events16 affected69 at risk EG0017 events4 affected34 at risk
Headache	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG00025 events17 affected69 at risk EG00110 events6 affected34 at risk

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

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	V114	Participants received a single 0.5 mL IM injection of V114 on Day 1.	0	70	13	69	52	69
EG001	Prevnar 13	Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.	0	34	8	34	27	34