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

• ClinicalTrials.gov Identifier: NCT03921424
• Recruitment Status: Completed
• First Posted: April 19, 2019
• Results First Posted: December 9, 2021
• Last Update Posted: December 9, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pneumococcal Infections	Biological: V114; Biological: Prevnar 13™; Biological: PNEUMOVAX™23	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 407 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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)
• Actual Study Start Date: November 5, 2019
• Actual Primary Completion Date: May 3, 2021
• Actual Study Completion Date: May 3, 2021

Arms and Interventions

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: 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.; 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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With a Solicited Injection-Site Adverse Event Following Vaccination With V114 or Prevnar 13™ [ Time Frame: Through 14 Days after Vaccination 1 (Up to Day 14) ]
   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.
2. Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With V114 or Prevnar 13™ [ Time Frame: Through 14 Days after Vaccination 1 (Up to Day 14) ]
   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.
3. 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 [ Time Frame: Through 6 Months after Vaccination 1 (Up to Day 194) ]
   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.
4. Anti-PnPs Serotype-specific IgG Geometric Mean Concentrations (GMCs) at 30 Days Following Vaccination With V114 or Prevnar 13™ [ Time Frame: Day 30 ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With a Solicited Injection-Site Adverse Event Following Vaccination With PNEUMOVAX™23 [ Time Frame: Through 14 Days after Vaccination 2 (Up to Day 84) ]
   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.
2. Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23 [ Time Frame: Through 14 Days after Vaccination 2 (Up to Day 84) ]
   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.
3. Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) at 30 Days Following Vaccination With V114 or Prevnar 13™ [ Time Frame: Day 30 ]
   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.
4. Anti-PnPs Serotype-specific OPA GMTs at 30 Days Following Vaccination With PNEUMOVAX™23 (Week 12) [ Time Frame: 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.
5. Anti-PnPs Serotype-specific IgG GMCs at 30 Days Following Vaccination With PNEUMOVAX™23 (Week 12) [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

South Africa

Perinatal HIV Research Unit ( Site 0042)

Johannesburg, Gauteng, South Africa, 1864

Wits Reproductive Health and HIV Institute (WRHI) ( Site 0043)

Johannesburg, Gauteng, South Africa, 2001

Family Clinic Research With UBUNTU ( Site 0045)

Cape Town, Western Cape, South Africa, 7505

Be Part Yoluntu Centre ( Site 0041)

Paarl, Western Cape, South Africa, 7626

Thailand

Faculty of Medicine - Khon Kaen University-Pediatrics ( Site 0063)

Amphoe Mueang, Khon Kaen, Thailand, 40002

Chulalongkorn University-Pediatrics ( Site 0062)

Bangkok, Krung Thep Maha Nakhon, Thailand, 10330

Faculty of Medicine Siriraj Hospital-Pediatric Infectious Diseases ( Site 0064)

Bangkok, Krung Thep Maha Nakhon, Thailand, 10700

CM Clinical Trial Unit-CM Clinical Trial Unit ( Site 0061)

Chiang Mai, Thailand, 50200

Ukraine

Community Instit Dnipropetrovsk Municipal clinical Hospital #21 ( Site 0088)

Dnipro, Dnipropetrovska Oblast, Ukraine, 49006

Dnipropetrovsk Regional Center of Socially Significant Diseases ( Site 0082)

Dnipro, Dnipropetrovska Oblast, Ukraine, 49115

Odesa Regional Center of Socially Significant Diseases ( Site 0083)

Odesa, Odeska Oblast, Ukraine, 65014

Vinnitsa Reg Cntr for AIDS Prevention-Control-Outpatient clinic dept ( Site 0086)

Vinnytsia, Vinnytska Oblast, Ukraine, 21000

Zaporizhzhya Regional Clinical Children's Hospital ( Site 0089)

Zaporizhzhya, Zaporizka Oblast, Ukraine, 69063

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:

Study Protocol and Statistical Analysis Plan  [PDF] March 27, 2019

More Information

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03921424
• Other Study ID Numbers: V114-030; V114-030 ( Other Identifier: Merck ); 2019-000341-12 ( EudraCT Number )
• First Posted: April 19, 2019
• Results First Posted: December 9, 2021
• Last Update Posted: December 9, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme LLC:

Pneumococcal conjugate vaccine (PCV), 15-valent, 22F, 33F

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome; HIV Infections; Pneumococcal Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs