Safety and Immunogenicity of V116 in Adults Living With Human Immunodeficiency Virus (HIV) (V116-007, STRIDE-7)

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, and immunogenicity of a pneumococcal 21-valent conjugate vaccine (V116) in persons living with human immunodeficiency virus (HIV), for the prevention of pneumococcal disease caused by the serotypes in the vaccine.

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 V116 in Adults Living With HIV

Conditions
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Pneumococcal Disease

Intervention / Treatment
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* Biological: V116
* Biological: Placebo
* Biological: PCV15
* Biological: PPSV23


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is infected with HIV Is receiving combination anti-retroviral therapy (ART) for ≥6 weeks before study entry with no intended changes to combination ART therapy for 3 months after randomization. Is vaccine-naïve Exclusion Criteria: Has a history of opportunistic infections ≤12 months before the first vaccination Has a history of noninfectious acquired immune deficiency syndrome-related illness Has a history of active hepatitis Has a history of invasive pneumococcal disease (IPD) or other culture-positive pneumococcal disease ≤3 years before Visit 2 (Day 1) Has a known hypersensitivity to any component of V116, PCV15, or PPSV23, including diphtheria toxoid Has a known or suspected congenital immunodeficiency, functional or anatomic asplenia, or history of autoimmune disease Has a coagulation disorder contraindicating intramuscular vaccinations. Has a recent illness with fever Has a known cancer malignancy that is progressing or has required active treatment <3 years before enrollment Had prior administration of PCV15 or PCV20. Is expected to receive any pneumococcal vaccine during the study outside of the protocol Has received systemic corticosteroids for ≥14 consecutive days and has not completed treatment ≥14 days before receipt of study vaccine Is currently receiving immunosuppressive therapy, including chemotherapeutic agents or other immunotherapies/immunomodulators used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease Has received any non-live vaccine ≤14 days before receipt of any study vaccine or is scheduled to receive any non-live vaccine ≤30 days after receipt of any study vaccine Has received any live virus vaccine ≤30 days before receipt of any study vaccine or is scheduled to receive any live virus vaccine ≤30 days after receipt of any study vaccine Has received a blood transfusion or blood products, including immunoglobulins ≤6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product ≤30 days after receipt of study vaccine Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 2 months of participating in this current study.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V116<br>Participants will receive a single intramuscular (IM) dose of V116 on Day 1, a single IM dose of placebo for PPSV23 on Week 8, and a single IM dose of PCV15 between 10 to 18 months after V116. | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the following pneumococcal polysaccharides (PnPs) antigen: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B in each 0.5 mL sterile solution<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;Biological: Placebo<br>* Saline in each 0.5 mL sterile solution<br>Biological: PCV15<br>* Pneumococcal 15-valent conjugate vaccine with 2 μg of each of the following PnPs antigen: 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; and 4 μg of PnPs antigen 6B in each 0.5 mL sterile suspension<br>* Other names: VAXNEUVANCE™;;|
| Active Comparator: PCV15 + PPSV23<br>Participants will receive a single IM dose of PCV15 on Day 1, and a single IM dose of PPSV23 on Week 8. | Biological: PCV15<br>* Pneumococcal 15-valent conjugate vaccine with 2 μg of each of the following PnPs antigen: 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; and 4 μg of PnPs antigen 6B in each 0.5 mL sterile suspension<br>* Other names: VAXNEUVANCE™;;Biological: PPSV23<br>* Pneumococcal 23-valent polyvalent vaccine with 25 μg of each of the following PnPs antigen: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F in each 0.5 mL sterile solution<br>* Other names: PNEUMOVAX™23;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with solicited injection-site AEs from Day 1 through Day 5 postvaccination in Part A | Percentage of participants with solicited injection-site AEs from Day 1 through Day 5 postvaccination in Part A | Up to 5 days after each vaccination in Part A | 
| Percentage of participants with solicited systemic AEs from Day 1 through Day 5 postvaccination in Part A | Percentage of participants with solicited systemic AEs from Day 1 through Day 5 postvaccination in Part A | Up to 5 days after each vaccination in Part A | 
| Percentage of participants with vaccine-related serious adverse events (SAEs) from Day 1 through the duration of participation in Part A | Percentage of participants with vaccine-related SAEs from Day 1 through the duration of participation in Part A | Up to 194 days in Part A | 
| Serotype-specific Opsonophagocytic activity (OPA) geometric mean titers (GMT) postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Serotype-specific OPA GMT postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Up to 114 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serotype-specific Immunoglobulin G (IgG) geometric mean concentration (GMC) postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Serotype-specific IgG GMC postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Up to 114 days | 
| Serotype-specific OPA geometric mean fold rises (GMFRs) postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Serotype-specific OPA GMFRs postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Up to 114 days | 
| Serotype-specific IgG GMFRs postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Serotype-specific IgG GMFRs postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Up to 114 days | 
| Percentage of participants with a >=4-fold rise in OPA responses from baseline (Day 1) to postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Percentage of participants with a >=4-fold rise in OPA responses from baseline (Day 1) to postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Baseline and up to 114 days | 
| Percentage of participants with a >=4-fold rise in IgG responses from baseline (Day 1) to postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Percentage of participants with a >=4-fold rise in IgG responses from baseline (Day 1) to postvaccination in Part A for 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116 | Baseline and up to 114 days | 
| Percentage of participants with solicited injection-site AEs from Day 1 of Part B through Day 5 postvaccination in Part B | Percentage of participants with solicited injection-site AEs from Day 1 of Part B through Day 5 postvaccination in Part B | Up to 5 days after vaccination in Part B | 
| Percentage of participants with solicited systemic AEs from Day 1 of Part B through Day 5 postvaccination in Part B | Percentage of participants with solicited systemic AEs from Day 1 of Part B through Day 5 postvaccination in Part B | Up to 5 days after vaccination in Part B | 
| Percentage of participants with vaccine-related SAEs from Day 1 of Part B through the duration of participation in Part B | Percentage of participants with vaccine-related SAEs from Day 1 of Part B through the duration of participation in Part B | Up to 44 days after vaccination in Part B |