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

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

Official Title
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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)

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114
* Biological: Prevnar 13™


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V114<br>Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 on Day 1. | Biological: V114<br>* 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<br>|
| Active Comparator: Prevnar 13™<br>Participants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1. | Biological: Prevnar 13™<br>* 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<br>|

What is the study measuring?
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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 |