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

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)

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.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Biological: V114; Biological: PNEUMOVAX™23; Biological: Prevnar 13™

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1864
      • Perinatal HIV Research Unit ( Site 0042)
    • Johannesburg, Gauteng, South Africa, 2001
      • Wits Reproductive Health and HIV Institute (WRHI) ( Site 0043)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7505
      • Family Clinic Research With UBUNTU ( Site 0045)
    • Paarl, Western Cape, South Africa, 7626
      • Be Part Yoluntu Centre ( Site 0041)
• Thailand
  • Chiang Mai, Thailand, 50200
    • CM Clinical Trial Unit-CM Clinical Trial Unit ( Site 0061)
  • Khon Kaen
    • Amphoe Mueang, Khon Kaen, Thailand, 40002
      • Faculty of Medicine - Khon Kaen University-Pediatrics ( Site 0063)
  • Krung Thep Maha Nakhon
    • Bangkok, Krung Thep Maha Nakhon, Thailand, 10330
      • Chulalongkorn University-Pediatrics ( Site 0062)
    • Bangkok, Krung Thep Maha Nakhon, Thailand, 10700
      • Faculty of Medicine Siriraj Hospital-Pediatric Infectious Diseases ( Site 0064)
• Ukraine
  • Dnipropetrovska Oblast
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49006
      • Community Instit Dnipropetrovsk Municipal clinical Hospital #21 ( Site 0088)
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49115
      • Dnipropetrovsk Regional Center of Socially Significant Diseases ( Site 0082)
  • Odeska Oblast
    • Odesa, Odeska Oblast, Ukraine, 65014
      • Odesa Regional Center of Socially Significant Diseases ( Site 0083)
  • Vinnytska Oblast
    • Vinnytsia, Vinnytska Oblast, Ukraine, 21000
      • Vinnitsa Reg Cntr for AIDS Prevention-Control-Outpatient clinic dept ( Site 0086)
  • Zaporizka Oblast
    • Zaporizhzhya, Zaporizka Oblast, Ukraine, 69063
      • Zaporizhzhya Regional Clinical Children's Hospital ( Site 0089)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V114; 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; 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.; Other Names: VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine; Biological: PNEUMOVAX™23; 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
Active Comparator: Prevnar 13™; 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: PNEUMOVAX™23; 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; Biological: Prevnar 13™; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Wilck M, Barnabas S, Chokephaibulkit K, Violari A, Kosalaraksa P, Yesypenko S, Chukhalova I, Dagan R, Richmond P, Mikviman E, Morgan L, Feemster K, Lupinacci R, Chiarappa J, Madhi SA, Bickham K, Musey L; V114-030 Study Group. A phase 3 study of safety and immunogenicity of V114, a 15-valent PCV, followed by PPSV23, in children living with HIV. AIDS. 2023 Mar 20. doi: 10.1097/QAD.0000000000003551. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Actual): May 3, 2021
• Study Completion (Actual): May 3, 2021

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Pneumococcal conjugate vaccine (PCV), 15-valent, 22F, 33F
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Pneumococcal Infections; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V114-030 (Other Identifier: Merck); 2019-000341-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No