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) (PNEU-WAY)

• ClinicalTrials.gov Identifier: NCT03480802
• Recruitment Status: Completed
• First Posted: March 29, 2018
• Results First Posted: November 25, 2020
• Last Update Posted: May 5, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

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™.

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: 302 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• 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 Adults Infected With HIV (PNEU-WAY)
• Actual Study Start Date: July 6, 2018
• Actual Primary Completion Date: September 16, 2019
• Actual Study Completion Date: January 17, 2020

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 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; Biological: PNEUMOVAX™23; 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
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 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; Biological: PNEUMOVAX™23; 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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With a Solicited Injection-site Adverse Event After Vaccination 1 [ Time Frame: Up to 5 days after Vaccination 1 (Up to Day 5) ]
   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.
2. Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 1 [ Time Frame: Up to 14 days after Vaccination 1 (Up to Day 14) ]
   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.
3. Percentage of Participants With a Vaccine-related Serious Adverse Event After Vaccination 1 [ Time Frame: Day 1 up to 8 weeks after Vaccination 1 (Up to Week 8) ]
   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.
4. Geometric Mean Titer (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) After Vaccination 1 [ Time Frame: Day 30 ]
   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.
5. Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) After Vaccination 1 [ Time Frame: Day 30 ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With a Solicited Injection-site Adverse Event After Vaccination 2 [ Time Frame: Up to 5 days after Vaccination 2 (Up to Day 61) ]
   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% CI were based on the exact binomial method proposed by Clopper and Pearson.
2. Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 2 [ Time Frame: Up to 14 days after Vaccination 2 (Up to Day 70) ]
   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.
3. Percentage of Participants With a Vaccine-related Serious Adverse Event After Vaccination 2 [ Time Frame: From Week 8 up to Month 6 ]
   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.
4. Geometric Mean Titer of Serotype-specific OPA After Vaccination 2 [ Time Frame: Week 12 ]
   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 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 MOPA. The MOPA 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.
5. Geometric Mean Concentration of Serotype-specific IgG After Vaccination 2 [ Time Frame: Week 12 ]
   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 ECL using the 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

United States, Florida

Bliss Healthcare Services ( Site 0010)

Orlando, Florida, United States, 32806

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

West Palm Beach, Florida, United States, 33407

United States, Texas

Saint Hope Foundation, Inc. ( Site 0009)

Houston, Texas, United States, 77060

The Crofoot Research Center, Inc. ( Site 0002)

Houston, Texas, United States, 77098

France

Hopital Gabriel Montpied ( Site 0084)

Clemont Ferrand, France, 63000

Hopital Saint Louis ( Site 0094)

Paris Cedex 10, France, 75475

Hopital Cochin du Paris ( Site 0089)

Paris, France, 75679

Peru

Via Libre ( Site 0043)

Lima, Peru, 15001

Investigaciones Medicas en Salud - INMENSA ( Site 0041)

Lima, Peru, 15046

South Africa

Chris Hani Baragwanath Hospital ( Site 0122)

Johannesburg, Soweto, South Africa, 1862

Be Part Yoluntu Centre ( Site 0123)

Paarl, Western Cape, South Africa, 7626

Thailand

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

Bangkok, Thailand, 10700

Research Institute for Health. ( Site 0182)

Chiang Mai, Thailand, 50200

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] June 1, 2018

More Information

Publications of Results:

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.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03480802
• Other Study ID Numbers: V114-018; V114-018 ( Other Identifier: Merck Protocol Number ); 2017-001909-32 ( EudraCT Number )
• First Posted: March 29, 2018
• Results First Posted: November 25, 2020
• Last Update Posted: May 5, 2022
• Last Verified: April 2022

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:

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

Additional relevant MeSH terms:

Pneumococcal Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs