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)

Pneumococcal Infections Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03480802
• Other study ID #: V114-018
• Secondary ID: V114-0182017-001
• Status: Completed
• Phase: Phase 3
• Start date: July 6, 2018
• Est. completion date: January 17, 2020

Study information

• Verified date: April 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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™.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 302
• Est. completion date: January 17, 2020
• Est. primary completion date: September 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
France	Hopital Gabriel Montpied ( Site 0084)	Clemont Ferrand
France	Hopital Cochin du Paris ( Site 0089)	Paris
France	Hopital Saint Louis ( Site 0094)	Paris Cedex 10
Peru	Investigaciones Medicas en Salud - INMENSA ( Site 0041)	Lima
Peru	Via Libre ( Site 0043)	Lima
South Africa	Chris Hani Baragwanath Hospital ( Site 0122)	Johannesburg	Soweto
South Africa	Be Part Yoluntu Centre ( Site 0123)	Paarl	Western Cape
Thailand	Siriraj Hosp (Prev&Social Med). ( Site 0183)	Bangkok
Thailand	Research Institute for Health. ( Site 0182)	Chiang Mai
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	Triple O Research Institute, P.A. ( Site 0011)	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  France,  Peru,  South Africa,  Thailand, 

References & Publications (1)

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 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 5 days after Vaccination 1 (Up to Day 5)
Primary	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.	Up to 14 days after Vaccination 1 (Up to Day 14)
Primary	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.	Day 1 up to 8 weeks after Vaccination 1 (Up to Week 8)
Primary	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.	Day 30
Primary	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.	Day 30
Secondary	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.	Up to 5 days after Vaccination 2 (Up to Day 61)
Secondary	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.	Up to 14 days after Vaccination 2 (Up to Day 70)
Secondary	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.	From Week 8 up to Month 6
Secondary	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.	Week 12
Secondary	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.	Week 12