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)
- Conditions
- Pneumococcal Infections
- Interventions
- Biological: Prevnar 13™Biological: V114Biological: PNEUMOVAX™23
- Registration Number
- NCT03480802
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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™.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 302
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prevnar 13™ 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) V114 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) V114 PNEUMOVAX™23 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) Prevnar 13™ PNEUMOVAX™23 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)
- Primary Outcome Measures
Name Time Method Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 1 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 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 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 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 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
Name Time Method Percentage of Participants With a Solicited Injection-site Adverse Event After Vaccination 2 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.
Percentage of Participants With a Solicited Systemic Adverse Event After Vaccination 2 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.
Percentage of Participants With a Vaccine-related Serious Adverse Event After Vaccination 2 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.
Geometric Mean Titer of Serotype-specific OPA After Vaccination 2 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.
Geometric Mean Concentration of Serotype-specific IgG After Vaccination 2 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.
Trial Locations
- Locations (13)
Investigaciones Medicas en Salud - INMENSA ( Site 0041)
🇵🇪Lima, Peru
Hopital Gabriel Montpied ( Site 0084)
🇫🇷Clemont Ferrand, France
Triple O Research Institute, P.A. ( Site 0011)
🇺🇸West Palm Beach, Florida, United States
Saint Hope Foundation, Inc. ( Site 0009)
🇺🇸Houston, Texas, United States
The Crofoot Research Center, Inc. ( Site 0002)
🇺🇸Houston, Texas, United States
Bliss Healthcare Services ( Site 0010)
🇺🇸Orlando, Florida, United States
Hopital Saint Louis ( Site 0094)
🇫🇷Paris Cedex 10, France
Hopital Cochin du Paris ( Site 0089)
🇫🇷Paris, France
Via Libre ( Site 0043)
🇵🇪Lima, Peru
Siriraj Hosp (Prev&Social Med). ( Site 0183)
🇹🇭Bangkok, Thailand
Chris Hani Baragwanath Hospital ( Site 0122)
🇿🇦Johannesburg, Soweto, South Africa
Research Institute for Health. ( Site 0182)
🇹🇭Chiang Mai, Thailand
Be Part Yoluntu Centre ( Site 0123)
🇿🇦Paarl, Western Cape, South Africa