A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by PNEUMOVAX™23 in Adults Infected With Human Immunodeficiency Virus (HIV) (V114-018)

NCT03480802 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V114-0182017-001909-32
• Study Type: interventional
• Target: 302
• Locations: 5 countries
• Sites: 13

Brief Summary

This study is designed to 1) describe the safety, tolerability, and immunogenicity of V114 and Prevnar 13™ in pneumococcal vaccine-naïve adults infected with HIV and to 2) describe the safety, tolerability, and immunogenicity of PNEUMOVAX™23 when administered 8 weeks after receipt of either V114 or Prevnar 13™.

Conditions

Pneumococcal Infections

Keywords

Conjugate pneumococcal vaccine, 15-valent, 22F, 33F

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With a Solicited Injection-site Adverse Event After Vaccination 1

  An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs consist of redness/erythema, swelling, and tenderness/pain. The 95% confidence interval (CI) were based on the exact binomial method proposed by Clopper and Pearson.

  Up to 5 days after Vaccination 1 (Up to Day 5)

• Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 1

  An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs consist of muscle pain (myalgia), joint pain (arthralgia), headache, and tiredness (fatigue). The 95% CI were based on the exact binomial method proposed by Clopper and Pearson.

  Up to 14 days after Vaccination 1 (Up to Day 14)

• Percentage of Participants With a Vaccine-related Serious Adverse Event After Vaccination 1

  A serious adverse event (SAE) is an AE that 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. Relatedness of an SAE to the study vaccine is determined by the investigator. The 95% CI were based on the exact binomial method proposed by Clopper and Pearson.

  Day 1 up to 8 weeks after Vaccination 1 (Up to Week 8)

• Geometric Mean Titer (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) After Vaccination 1

  Opsonization of pneumococci for phagocytosis is an important mechanism by which antibodies to polysaccharides protect against disease in vivo. Sera from participants was used to measure geometric mean titer (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 two serotypes (22F and 33F) which are unique to V114, using the Multiplexed Opsonophagocytic Assay (MOPA). This assay reads the reciprocal of the highest dilution (1/dil) that gives ≥50% bacterial killing, as determined by comparison to assay background controls. The 95% CIs were derived by exponentiating the CIs of the mean of the natural log values based on the t-distribution.

  Day 30

• Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) After Vaccination 1

  The geometric mean concentration of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by multiplex electrochemiluminescence (ECL) using the pneumococcal electrochemiluminescence (PnECL) v2.0 assay, based on the Meso-Scale Discovery technology, which employs disposable multi-spot microtiter plates. The 95% CIs were derived by exponentiating the CIs of the mean of the natural log values based on the t-distribution.

  Day 30

Secondary Outcomes (5)

• Percentage of Participants With a Solicited Injection-site Adverse Event After Vaccination 2

  Up to 5 days after Vaccination 2 (Up to Day 61)

• Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 2

  Up to 14 days after Vaccination 2 (Up to Day 70)

• Percentage of Participants With a Vaccine-related Serious Adverse Event After Vaccination 2

  From Week 8 up to Month 6

• Geometric Mean Titer of Serotype-specific OPA After Vaccination 2

  Week 12

• Geometric Mean Concentration of Serotype-specific IgG After Vaccination 2

  Week 12

Study Arms (2)

V114

EXPERIMENTAL

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; Biological: PNEUMOVAX™23

Prevnar 13™

ACTIVE COMPARATOR

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™; Biological: PNEUMOVAX™23

Interventions

V114 BIOLOGICAL

15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and Merck Aluminum Phosphate Adjuvant (125 mcg) in each 0.5 mL dose

V114

Prevnar 13™ BIOLOGICAL

13-valent pneumococcal conjugate vaccine with 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

Prevnar 13™

PNEUMOVAX™23 BIOLOGICAL

23-valent pneumococcal polysaccharide vaccine with serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F (25 mcg each) in each 0.5 mL dose

Prevnar 13™; V114

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female infected with human immunodeficiency virus (HIV) and Cluster of Differentiation 4+ (CD4+) cell count ≥50 cells/µL and plasma HIV ribonucleic acid (RNA) \<50,000 copies/mL
• Receiving combination anti-retroviral therapy (ART) for at least 6 weeks before enrollment with no intention of changing therapy for 3 months after randomization
• 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 study vaccine.

You may not qualify if:

• History of opportunistic infections within 12 months before the first study vaccination
• History of non-infectious acquired immune deficiency syndrome-related illness such as Kaposi's sarcoma, wasting syndrome, or HIV-associated nephropathy
• History of invasive pneumococcal disease
• Known hypersensitivity to any vaccine component
• Known or suspected congenital immunodeficiency, functional or anatomic asplenia, or history of autoimmune disease
• Coagulation disorder contraindicating intramuscular vaccination
• History of malignancy ≤5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• Female participant: positive urine or serum pregnancy test
• Prior administration of any pneumococcal vaccine
• Received systemic corticosteroids for ≥14 consecutive days and have not completed within 30 days of enrollment
• Received immunosuppressive therapy
• 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 recent history of drug or alcohol abuse or dependence.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (13)

Bliss Healthcare Services ( Site 0010)

Orlando, Florida, 32806, United States

Location

Triple O Research Institute, P.A. ( Site 0011)

West Palm Beach, Florida, 33407, United States

Location

Saint Hope Foundation, Inc. ( Site 0009)

Houston, Texas, 77060, United States

Location

The Crofoot Research Center, Inc. ( Site 0002)

Houston, Texas, 77098, United States

Location

Hopital Gabriel Montpied ( Site 0084)

Clemont Ferrand, 63000, France

Location

Hopital Saint Louis ( Site 0094)

Paris, 75475, France

Location

Hopital Cochin du Paris ( Site 0089)

Paris, 75679, France

Location

Via Libre ( Site 0043)

Lima, 15001, Peru

Location

Investigaciones Medicas en Salud - INMENSA ( Site 0041)

Lima, 15046, Peru

Location

Chris Hani Baragwanath Hospital ( Site 0122)

Johannesburg, Soweto, 1862, South Africa

Location

Be Part Yoluntu Centre ( Site 0123)

Paarl, Western Cape, 7626, South Africa

Location

Siriraj Hosp (Prev&Social Med). ( Site 0183)

Bangkok, 10700, Thailand

Location

Research Institute for Health. ( Site 0182)

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• Mohapi L, Pinedo Y, Osiyemi O, Supparatpinyo K, Ratanasuwan W, Molina JM, Dagan R, Tamms G, Sterling T, Zhang Y, Pedley A, Hartzel J, Kan Y, Hurtado K, Musey L, Simon JK, Buchwald UK; V114-018 (PNEU-WAY) study group. Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in adults living with HIV. AIDS. 2022 Mar 1;36(3):373-382. doi: 10.1097/QAD.0000000000003126.

  PMID: 34750291 RESULT

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2018
• First Posted: March 29, 2018
• Study Start: July 6, 2018
• Primary Completion: September 16, 2019
• Study Completion: January 17, 2020
• Last Updated: May 5, 2022
• Results First Posted: November 25, 2020

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

ZA (2); PE (2); TH (2); US (4); FR (3)