Safety and Immunogenicity of V114 in Children Infected With Human Immunodeficiency Virus (HIV) (V114-030/PNEU-WAY PED)

Study Overview
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Brief Summary
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This is a study of V114 in children infected with HIV. Participants will be randomly assigned in a 1:1 ratio to receive either V114 or Prevnar 13™ followed 8 weeks later by a single dose of PNEUMOVAX™23. The primary objectives of this study are to evaluate the safety and tolerability of V114 in children 6 to 17 years of age inclusive infected with HIV and to evaluate the anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) at 30 days following vaccination with V114 or Prevnar 13™ by each vaccination group. There are no formal hypotheses.

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 Followed by Administration of PNEUMOVAX™23 Eight Weeks Later in Children Infected With Human Immunodeficiency Virus (HIV) (PNEU-WAY PED)

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114
* Biological: Prevnar 13™
* Biological: PNEUMOVAX™23


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between the ages of 6 and 17 years (inclusive) infected with HIV and has a Cluster of Differentiation 4+ (CD4+) T-cell count ≥200 cells/µL and plasma HIV ribonucleic acid (RNA) <50,000 copies/mL Is Pneumococcal Conjugate Vaccine (PCV) naïve, previously vaccinated with a <13-valent PCV, partially vaccinated with Prevnar 13™, or has a history of previous Prevnar 13™ vaccination ≥3 years before Visit 2 (Day 1) Is PnPs vaccine naïve or has a history of 1 previous PnPs vaccination ≥5 years before Visit 2 (Day 1) Female participant: not pregnant, not breastfeeding and 1) not of childbearing potential, or 2) of childbearing potential and agrees to practice contraception through 6 weeks after administration of last dose of the study vaccine. Exclusion Criteria: History of World Health Organization (WHO) HIV classification of clinical Stage 4 disease within the past 12 months History of invasive pneumococcal disease Known hypersensitivity to any vaccine component Known or suspected congenital immunodeficiency (other than HIV infection), functional or anatomic asplenia, or history of autoimmune disease Bleeding disorder contraindicating intramuscular vaccinations 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 Female participant: positive urine or serum pregnancy test Expect to receive any pneumococcal vaccine during the study outside of the protocol 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 Received a blood transfusion or blood products within 6 months of enrollment Participated in another clinical study of an investigational product within 2 months of enrollment Current user of recreational or illicit drugs or history of drug or alcohol abuse or dependence

Ages Eligible for Study
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Minimum Age: 6 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: Quadruple


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 (Vaccination 1) and a single 0.5 mL IM injection of PNEUMOVAX™23 at Week 8 (Vaccination 2) | Biological: V114<br>* 15-valent pneumococcal conjugate vaccine containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) present in Prevnar 13™ plus 2 additional serotypes (22F, 33F) in each 0.5 mL dose.<br>* Other names: Pneumococcal 15-Valent Conjugate Vaccine;Biological: PNEUMOVAX™23<br>* 23-valent pneumococcal polysaccharide vaccine containing 23 serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F) 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 (Vaccination 1) and a single 0.5 mL IM injection of PNEUMOVAX™23 at Week 8 (Vaccination 2) | Biological: Prevnar 13™<br>* 13-valent pneumococcal conjugate vaccine containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) in each 0.5 mL dose.<br>Biological: PNEUMOVAX™23<br>* 23-valent pneumococcal polysaccharide vaccine containing 23 serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F) 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 Following Vaccination With V114 or Prevnar 13™ | An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following Vaccination 1 with either V114 or Prevnar 13™, the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were redness/erythema, hard lump/induration, tenderness/pain, and swelling. | Through 14 Days after Vaccination 1 (Up to Day 14) | 
| Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With V114 or Prevnar 13™ | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following Vaccination 1 with either V114 or Prevnar 13™, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were joint pain/arthralgia, tiredness/fatigue, headache, muscle pain/myalgia, and hives or welts/urticaria. | Through 14 Days after Vaccination 1 (Up to Day 14) | 
| Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE) Following Vaccination 1 (V114 or Prevnar 13™) or Vaccination 2 (PNEUMOVAX™23) Through Completion of Study | An 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 an other important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following Vaccination 1 (with either V114 or Prevnar 13™) or Vaccination 2 (PNEUMOVAX™23) through completion of study participation was reported. | Through 6 Months after Vaccination 1 (Up to Day 194) | 
| Anti-PnPs Serotype-specific IgG Geometric Mean Concentrations (GMCs) at 30 Days Following Vaccination With V114 or Prevnar 13™ | The GMC of serotype-specific IgG for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Solicited Injection-Site Adverse Event Following Vaccination With PNEUMOVAX™23 | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following Vaccination 2 with PNEUMOVAX™23 (PPV23), the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were redness/erythema, hard lump/induration, tenderness/pain, and swelling. | Through 14 Days after Vaccination 2 (Up to Day 84) | 
| Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23 | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following Vaccination 2 with PNEUMOVAX™23, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were joint pain/arthralgia, tiredness/fatigue, headache, muscle pain/myalgia, and hives or welts/urticaria. | Through 14 Days after Vaccination 2 (Up to Day 84) | 
| Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) at 30 Days Following Vaccination With V114 or Prevnar 13™ | The GMT of serotype-specific OPA for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplexed opsonophagocytic assay. | Day 30 | 
| Anti-PnPs Serotype-specific OPA GMTs at 30 Days Following Vaccination With PNEUMOVAX™23 (Week 12) | The GMT of serotype-specific OPA for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplexed opsonophagocytic assay. | Week 12 | 
| Anti-PnPs Serotype-specific IgG GMCs at 30 Days Following Vaccination With PNEUMOVAX™23 (Week 12) | The GMC of serotype-specific IgG for the serotypes contained in V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumococcal conjugate vaccine (PCV), 15-valent, 22F, 33F