Clinical trial NCT03731182: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Children With Sickle Cell Disease (V114-023/PNEU-SICKLE)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-11-06
Enrollment: 104
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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


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.

Primary outcomes:
measure: Percentage of Participants With a Solicited Injection-site Adverse Event
timeFrame: Up to 14 days post-vaccination
measure: Percentage of Participants With a Solicited Systemic Adverse Event
timeFrame: Up to 14 days post-vaccination
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event
timeFrame: Up to 6 months post-vaccination
measure: Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) at Day 30
timeFrame: Day 30
Secondary outcomes:
measure: Geometric Mean Titer (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) at Day 30
timeFrame: Day 30
measure: Geometric Mean Fold Rise (GMFR) in Serotype-specific IgG From Day 1 (Baseline) to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: GMFR in Serotype-specific OPA From Day 1 (Baseline) to Day 30
timeFrame: Day 1 (Baseline) and Day 30
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Nemours/Alfred I. duPont Hospital for Children ( Site 0113)
state: Delaware
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta ( Site 0100)
state: Georgia
city: Detroit
country: United States
facility: Children's Hospital of Michigan ( Site 0111)
state: Michigan
city: Newark
country: United States
facility: Newark Beth Israel Medical Center ( Site 0115)
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester Medical Center ( Site 0105)
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center ( Site 0101)
state: Ohio
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte ( Site 0200)
state: MG
city: Salvador
country: Brazil
facility: Hospital Santo Antonio - Obras Sociais Irma Dulce ( Site 0205)
city: Sao Paulo
country: Brazil
facility: Santa Casa de Misericordia de Sao Paulo ( Site 0202)
city: Barranquilla
country: Colombia
facility: Clinica de la Costa Ltda. ( Site 0300)
state: Atlantico
city: Cali
country: Colombia
facility: Centro de Estudios en Infectologia Pediatrica SAS ( Site 0301)
state: Valle Del Cauca
city: Distrito Nacional
country: Dominican Republic
facility: Fundacion Dominicana de Perinatologia PRO BEBE INC ( Site 0402)
state: Santo Domingo
city: Santo Domingo
country: Dominican Republic
facility: Clinical Research Republica Dominicana ( Site 0401)
city: Santo Domingo
country: Dominican Republic
facility: Caimed Dominicana S.A.S ( Site 0400)
city: Athens
country: Greece
facility: Agia Sophia Children s Hospital ( Site 0700)
city: Thessaloniki
country: Greece
facility: Hippokration General Hospital of Thessaloniki ( Site 0701)
city: Genova
country: Italy
facility: Ospedale San Martino ( Site 0800)
city: Panama
country: Panama
facility: Cevaxin ( Site 0500)
city: Panama
country: Panama
facility: Cevaxin ( Site 0502)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.