A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Children With Sickle Cell Disease (V114-023/PNEU-SICKLE)

A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator Controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Children With Sickle Cell Disease (PNEU-SICKLE)

This study is designed to describe the safety, tolerability, and immunogenicity of V114 in children with sickle cell disease.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Biological: V114; Biological: Prevnar 13™

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Salvador, Brazil, 40420-000
    • Hospital Santo Antonio - Obras Sociais Irma Dulce ( Site 0205)
  • Sao Paulo, Brazil, 01221-900
    • Santa Casa de Misericordia de Sao Paulo ( Site 0202)
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Santa Casa de Misericordia de Belo Horizonte ( Site 0200)
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080020
      • Clinica de la Costa Ltda. ( Site 0300)
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760045
      • Centro de Estudios en Infectologia Pediatrica SAS ( Site 0301)
• Dominican Republic
  • Santo Domingo, Dominican Republic, 10122
    • Clinical Research Republica Dominicana ( Site 0401)
  • Santo Domingo, Dominican Republic, 10205
    • Caimed Dominicana S.A.S ( Site 0400)
  • Santo Domingo
    • Distrito Nacional, Santo Domingo, Dominican Republic, 10204
      • Fundacion Dominicana de Perinatologia PRO BEBE INC ( Site 0402)
• Greece
  • Athens, Greece, 115 27
    • Agia Sophia Children s Hospital ( Site 0700)
  • Thessaloniki, Greece, 546 42
    • Hippokration General Hospital of Thessaloniki ( Site 0701)
• Italy
  • Genova, Italy, 16132
    • Ospedale San Martino ( Site 0800)
• Panama
  • Panama, Panama, 0816-00383
    • Cevaxin ( Site 0500)
  • Panama, Panama, 0816-00383
    • Cevaxin ( Site 0502)
• United States
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours/Alfred I. duPont Hospital for Children ( Site 0113)
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Children's Healthcare of Atlanta ( Site 0100)
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan ( Site 0111)
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center ( Site 0115)
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center ( Site 0105)
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center ( Site 0101)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V114; Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 on Day 1.	Biological: V114; 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
Active Comparator: Prevnar 13™; Participants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1.	Biological: Prevnar 13™; Prevnar 13™ pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg) and 6B (4.4 mcg) in each 0.5 ml dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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
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).	Day 1 (Baseline) and Day 30
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).	Day 1 (Baseline) and Day 30

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Quinn CT, Wiedmann RT, Jarovsky D, Lopez-Medina E, Rodriguez HM, Papa M, Boggio G, Shou Q, Dagan R, Richmond PC, Feemster K, McFetridge R, Tamms GM, Lupinacci R, Musey L, Bickham K. Safety and Immunogenicity of V114, a 15-valent Pneumococcal Conjugate Vaccine, in Children with Sickle Cell Disease (PNEU-SICKLE). Blood Adv. 2022 Nov 16. pii: bloodadvances.2022008037. doi: 10.1182/bloodadvances.2022008037. [Epub ahead of print]

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2019
• Primary Completion (Actual): June 8, 2020
• Study Completion (Actual): June 8, 2020

Study Registration Dates

• First Submitted: November 2, 2018
• First Submitted That Met QC Criteria: November 2, 2018
• First Posted (Actual): November 6, 2018

Study Record Updates

• Last Update Posted (Actual): June 16, 2021
• Last Update Submitted That Met QC Criteria: May 21, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Hematologic Diseases; Genetic Diseases, Inborn; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Pneumococcal Infections; Anemia, Sickle Cell; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V114-023 (Other Identifier: Merck Protocol Number); 2018-001152-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No