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

Pneumococcal Infections Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03731182
• Other study ID #: V114-023
• Secondary ID: V114-0232018-001
• Status: Completed
• Phase: Phase 3
• Start date: January 23, 2019
• Est. completion date: June 8, 2020

Study information

• Verified date: May 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: June 8, 2020
• Est. primary completion date: June 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Pneumococcal Infections

Intervention

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
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Brazil,  Colombia,  Dominican Republic,  Greece,  Italy,  Panama, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 14 days post-vaccination
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).	Up to 14 days post-vaccination
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.	Up to 6 months post-vaccination
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.	Day 30
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).	Day 30
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).	Day 1 (Baseline) and Day 30
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).	Day 1 (Baseline) and Day 30