Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-028)

• ClinicalTrials.gov Identifier: NCT03848065
• Recruitment Status: Completed
• First Posted: February 20, 2019
• Last Update Posted: September 20, 2021
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of V114 administered subcutaneously or intramuscularly in healthy Japanese infants (3 months of age).

Condition or disease	Intervention/treatment	Phase
Pneumococcal Infections	Biological: V114; Biological: Pneumococcal 13-valent Conjugate Vaccine (PCV13)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 133 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase I, Double-Blind, Randomized, Multicenter Trial of the Safety,Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants
• Actual Study Start Date: April 2, 2019
• Actual Primary Completion Date: June 24, 2020
• Actual Study Completion Date: June 24, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: V114-SC; 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).	Biological: V114; 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.; Other Names: VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine
Experimental: V114-IM; 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).	Biological: V114; 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.; Other Names: VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine
Active Comparator: PCV13-SC; 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).	Biological: Pneumococcal 13-valent Conjugate Vaccine (PCV13); 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F, serotype 6B in each 0.5. mL dose.; Other Name: PREVNAR 13®

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants with a Solicited Injection-site Adverse Event [ Time Frame: Day 1 to Day 14 postvaccination ]
   An adverse event (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 will be redness, swelling, and pain/tenderness.
2. Percentage of Participants with a Solicited Systemic Adverse Event [ Time Frame: Day 1 to Day 14 postvaccination ]
   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 will be muscle pain, joint pain, headache, and tiredness.
3. Percentage of Participants with a Vaccine-related Serious Adverse Event [ Time Frame: Day 1 to 1 month postvaccination (post-dose 4) ]
   A serious adverse event (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 will be determined by the investigator.

Secondary Outcome Measures :

1. Percentage of Participants Meeting the Serotype-specific Immunoglobulin G (IgG) Threshold of ≥0.35 µg/mL [ Time Frame: One month postvaccination (post-dose 3) ]
   Assess the antipneumococcal polysaccharide (PnPs) serotype-specific IgG response rates (percentage of participants meeting serotype-specific IgG threshold value of ≥0.35 μg/mL) as measured by the pneumococcal polysaccharide electrochemiluminescence (Pn ECL) assay
2. Serotype-specific IgG Geometric Mean Concentrations (GMCs) [ Time Frame: One month postvaccination (post-dose 3) ]
   Assess the anti-PnPs serotype-specific IgG GMCs as measured in the Pn ECL assay.

Eligibility Criteria

• Ages Eligible for Study: 3 Months to 3 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Japan

Meitetsu Hospital ( Site 2805)

Nagoya, Aichi, Japan, 451-8511

Sotobo Children's Clinic ( Site 2807)

Isumi, Chiba, Japan, 299-4503

Hidaka Children's Clinic ( Site 2803)

Dazaifu, Fukuoka, Japan, 818-0134

Isesaki Municipal Hospital ( Site 2806)

Isesaki, Gunma, Japan, 372-0817

Kawasaki Municipal Hospital ( Site 2802)

Kawasaki, Kanagawa, Japan, 210-0013

Yokosuka Kyosai Hospital ( Site 2804)

Yokosuka, Kanagawa, Japan, 238-8558

Suita Municipal Hospital ( Site 2801)

Suita, Osaka, Japan, 564-8567

Kobayashi Pediatric Clinic ( Site 2816)

Fujieda, Shizuoka, Japan, 426-0067

Nishida Kodomo Clinic ( Site 2811)

Tama, Tokyo, Japan, 206-0025

Fukui Aiiku Hospital ( Site 2809)

Fukui, Japan, 910-0833

Fukui-ken Saiseikai Hospital ( Site 2813)

Fukui, Japan, 918-8503

Kubota Children's Clinic ( Site 2815)

Osaka, Japan, 544-0033

Japanese Red Cross Shizuoka Hospital ( Site 2817)

Shizuoka, Japan, 420-0853

Hosaka Children's Clinic ( Site 2814)

Tokyo, Japan, 112-0001

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT03848065
• Other Study ID Numbers: V114-028; V114-028 ( Other Identifier: Merck Protocol Number ); 194669 ( Registry Identifier: JAPIC-CTI )
• First Posted: February 20, 2019
• Last Update Posted: September 20, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:

Pneumococcal Vaccines

Additional relevant MeSH terms:

Pneumococcal Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs