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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 302
- Locations
- 26
- Primary Endpoint
- Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 1
Study Overview
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™.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Outcomes
Primary Outcomes
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.
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.
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.
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.
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 Outcomes
- 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)