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)

Merck Sharp & Dohme LLC302 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

302

Conditions

Pneumococcal Infections

Interventions

V114BIOLOGICAL

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

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

PNEUMOVAX™23BIOLOGICAL

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (13)

Bliss Healthcare Services ( Site 0010)

Orlando, Florida, United States

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

West Palm Beach, Florida, United States

Saint Hope Foundation, Inc. ( Site 0009)

Houston, Texas, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: Up to 5 days after Vaccination 2 (Up to Day 61)

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)

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

Time frame: From Week 8 up to Month 6

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.

Time frame: Week 12

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.

Time frame: Week 12