Back to resultsA 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)
Primary Purpose
Pneumococcal Infections
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
V114
Prevnar 13™
PNEUMOVAX™23
Sponsored by
About this trial
This is an interventional prevention trial for Pneumococcal Infections focused on measuring Conjugate pneumococcal vaccine, 15-valent, 22F, 33F
Eligibility 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.
Sites / Locations
- Bliss Healthcare Services ( Site 0010)
- Triple O Research Institute, P.A. ( Site 0011)
- Saint Hope Foundation, Inc. ( Site 0009)
- The Crofoot Research Center, Inc. ( Site 0002)
- Hopital Gabriel Montpied ( Site 0084)
- Hopital Saint Louis ( Site 0094)
- Hopital Cochin du Paris ( Site 0089)
- Via Libre ( Site 0043)
- Investigaciones Medicas en Salud - INMENSA ( Site 0041)
- Chris Hani Baragwanath Hospital ( Site 0122)
- Be Part Yoluntu Centre ( Site 0123)
- Siriraj Hosp (Prev&Social Med). ( Site 0183)
- Research Institute for Health. ( Site 0182)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
V114
Prevnar 13™
Arm Description
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)
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)
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
Secondary Outcome Measures
Percentage of Participants With a Solicited Injection-site Adverse Event After Vaccination 2
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.
Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 2
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.
Percentage of Participants With a Vaccine-related Serious Adverse Event After Vaccination 2
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.
Geometric Mean Titer of Serotype-specific OPA After Vaccination 2
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.
Geometric Mean Concentration of Serotype-specific IgG After Vaccination 2
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03480802
Brief Title
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)
Acronym
PNEU-WAY
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
July 6, 2018 (Actual)
Primary Completion Date
September 16, 2019 (Actual)
Study Completion Date
January 17, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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™.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumococcal Infections
Keywords
Conjugate pneumococcal vaccine, 15-valent, 22F, 33F
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
302 (Actual)
8. Arms, Groups, and Interventions
Arm Title
V114
Arm Type
Experimental
Arm Description
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)
Arm Title
Prevnar 13™
Arm Type
Active Comparator
Arm Description
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)
Intervention Type
Biological
Intervention Name(s)
V114
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Prevnar 13™
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
PNEUMOVAX™23
Intervention Description
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
Primary Outcome Measure Information:
Title
Percentage of Participants With a Solicited Injection-site Adverse Event After Vaccination 1
Description
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.
Time Frame
Up to 5 days after Vaccination 1 (Up to Day 5)
Title
Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 1
Description
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.
Time Frame
Up to 14 days after Vaccination 1 (Up to Day 14)
Title
Percentage of Participants With a Vaccine-related Serious Adverse Event After Vaccination 1
Description
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.
Time Frame
Day 1 up to 8 weeks after Vaccination 1 (Up to Week 8)
Title
Geometric Mean Titer (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) After Vaccination 1
Description
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.
Time Frame
Day 30
Title
Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) After Vaccination 1
Description
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.
Time Frame
Day 30
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Solicited Injection-site Adverse Event After Vaccination 2
Description
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.
Time Frame
Up to 5 days after Vaccination 2 (Up to Day 61)
Title
Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 2
Description
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.
Time Frame
Up to 14 days after Vaccination 2 (Up to Day 70)
Title
Percentage of Participants With a Vaccine-related Serious Adverse Event After Vaccination 2
Description
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.
Time Frame
From Week 8 up to Month 6
Title
Geometric Mean Titer of Serotype-specific OPA After Vaccination 2
Description
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.
Time Frame
Week 12
Title
Geometric Mean Concentration of Serotype-specific IgG After Vaccination 2
Description
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.
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Bliss Healthcare Services ( Site 0010)
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Triple O Research Institute, P.A. ( Site 0011)
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Saint Hope Foundation, Inc. ( Site 0009)
City
Houston
State/Province
Texas
ZIP/Postal Code
77060
Country
United States
Facility Name
The Crofoot Research Center, Inc. ( Site 0002)
City
Houston
State/Province
Texas
ZIP/Postal Code
77098
Country
United States
Facility Name
Hopital Gabriel Montpied ( Site 0084)
City
Clemont Ferrand
ZIP/Postal Code
63000
Country
France
Facility Name
Hopital Saint Louis ( Site 0094)
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Hopital Cochin du Paris ( Site 0089)
City
Paris
ZIP/Postal Code
75679
Country
France
Facility Name
Via Libre ( Site 0043)
City
Lima
ZIP/Postal Code
15001
Country
Peru
Facility Name
Investigaciones Medicas en Salud - INMENSA ( Site 0041)
City
Lima
ZIP/Postal Code
15046
Country
Peru
Facility Name
Chris Hani Baragwanath Hospital ( Site 0122)
City
Johannesburg
State/Province
Soweto
ZIP/Postal Code
1862
Country
South Africa
Facility Name
Be Part Yoluntu Centre ( Site 0123)
City
Paarl
State/Province
Western Cape
ZIP/Postal Code
7626
Country
South Africa
Facility Name
Siriraj Hosp (Prev&Social Med). ( Site 0183)
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Research Institute for Health. ( Site 0182)
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
34750291
Citation
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.
Results Reference
result
Learn more about this trial
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)
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