A Study to Evaluate the Interchangeability of V114 and Prevnar 13™ in Healthy Infants (V114-027/PNEU-DIRECTION)

Pneumococcal Infections Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Interchangeability of V114 and Prevnar 13™ With Respect to Safety, Tolerability, and Immunogenicity in Healthy Infants (PNEU-DIRECTION)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03620162
• Other study ID #: V114-027
• Secondary ID: V114-0272018-001
• Status: Completed
• Phase: Phase 3
• Start date: October 18, 2018
• Est. completion date: December 14, 2020

Study information

• Verified date: January 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to evaluate the safety, tolerability, and immunogenicity of the Pneumococcal Conjugate Vaccines (PCVs) V114 and Prevnar 13™ in healthy infants switched from Prevnar 13™ to V114 during the four-dose PCV immunization schedule.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 900
• Est. completion date: December 14, 2020
• Est. primary completion date: December 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 42 Days to 90 Days

Eligibility

Inclusion Criteria:

• Is Healthy, based on clinical judgment of the investigator

• Has a legally acceptable representative who understands the study procedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent.

Exclusion Criteria:

• Has a history of invasive pneumococcal disease (positive blood culture, positive cerebrospinal fluid culture, or other sterile site) or known history of other culture positive pneumococcal disease

• Has a known hypersensitivity to any component of the pneumococcal conjugate vaccine (PCV), any component of the licensed pediatric vaccines to be administered concomitantly in the study, or any diphtheria toxoid-containing vaccine

• Has any contraindication to the concomitant study vaccines being administered in the study

• Has a known or suspected impairment of immunological function

• Has a history of congenital or acquired immunodeficiency

• Has or his/her mother has a documented human immunodeficiency virus (HIV) infection

• Has or his/her mother has a documented hepatitis B surface antigen - positive test

• Has known or history of functional or anatomic asplenia

• Has failure to thrive based on the clinical judgment of the investigator

• Has a known coagulation disorder contraindicating intramuscular vaccination

• Has a history of autoimmune disease (including but not limited to systemic lupus erythematosus, antiphospholipid syndrome, Behcet's disease, autoimmune thyroid disease, polymyositis and dermatomyositis, scleroderma, type 1 diabetes mellitus, or other autoimmune disorders)

• Has a known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders

• Has received a dose of any pneumococcal vaccine prior to study entry

• Has received >1 dose of monovalent hepatitis B vaccine or hepatitis B based combination vaccine prior to study entry

• Has received a dose of rotavirus vaccine prior to study entry

• Has received a blood transfusion or blood products, including immunoglobulins

• Has participated in another clinical study of an investigational product before the beginning or anytime during the duration of the current clinical study

• Has any other reason that, in the opinion of the investigator, may interfere with the evaluation required by the study

• Has an immediate family member (e.g., parent/legal guardian or sibling) who is investigational site or Sponsor staff directly involved with this study.

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

Biological:
• Prevnar 13™
Prevnar 13™ contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each) and 6B (4.4 mcg) in each 0.5 mL dose given via IM injection.
• V114
V114 contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), and serotype 6B (4 mcg) in each 0.5 mL dose given via IM injection.
• RotaTeq™
RotaTeq™ live, pentavalent Rotavirus vaccine given as background treatment via oral solution.
• Pentacel™
Pentacel™ Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine, given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.
• RECOMBIVAX HB™
RECOMBIVAX HB™ Hepatitis B Vaccine (Recombinant), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.
• HIBERIX™
HIBERIX™ Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.
• M-M-R™ II
M-M-R™ II (Measles, Mumps, and Rubella Virus Vaccine Live), given as background treatment via subcutaneous (SC) injection in the opposite limb to V114 and Prevnar 13™ administration.
• VARIVAX™
VARIVAX™ Varicella Virus Vaccine Live, given as background treatment via SC injection in the opposite limb to V114 and Prevnar 13™ administration.

Locations

Country	Name	City	State
Puerto Rico	Cooperativa de Facultad Medica Sanacoop ( Site 0057)	Bayamon
Puerto Rico	Clinical Research of Puerto Rico ( Site 0050)	Guayama
Puerto Rico	CAIMED Center - Ponce School of Medicine ( Site 0053)	Ponce
Puerto Rico	San Juan Hospital ( Site 0056)	San Juan
Puerto Rico	University of Puerto Rico ( Site 0051)	San Juan
Thailand	Chulalongkorn University ( Site 0092)	Bangkok
Thailand	Siriaj Hospital ( Site 0091)	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital ( Site 0090)	Chiang Mai
Thailand	Srinagarind Hospital. Khon Kaen University ( Site 0093)	Muang	Khon Kaen
Turkey	Hacettepe University Faculty of Medicine ( Site 0070)	Ankara
Turkey	Eskisehir Osmangazi University Faculty of Medicine ( Site 0071)	Eskisehir
Turkey	Ege University Medical Faculty Hospital ( Site 0072)	Izmir
United States	Kentucky Pediatric/Adult Research Inc ( Site 0011)	Bardstown	Kentucky
United States	Alabama Clinical Therapeutics ( Site 0015)	Birmingham	Alabama
United States	Coastal Pediatric Research ( Site 0006)	Charleston	South Carolina
United States	Davita Medical Group ( Site 0012)	Colorado Springs	Colorado
United States	Southeastern Pediatric Associates, P.A. ( Site 0002)	Dothan	Alabama
United States	Pediatric Associates of Fall River ( Site 0021)	Fall River	Massachusetts
United States	Ventavia Research Group LLC ( Site 0017)	Fort Worth	Texas
United States	University of Texas Medical Branch ( Site 0023)	Galveston	Texas
United States	Parkside Pediatric ( Site 0007)	Greenville	South Carolina
United States	Children's Clinic of Jonesboro, PA ( Site 0022)	Jonesboro	Arkansas
United States	Holston Medical Group ( Site 0018)	Kingsport	Tennessee
United States	Midwest Children's Health Research Institute, LLC ( Site 0001)	Lincoln	Nebraska
United States	Midwest Children's Health Research Institute, LLC ( Site 0003)	Lincoln	Nebraska
United States	Midwest Children's Health Research Institute, LLC ( Site 0004)	Lincoln	Nebraska
United States	Midwest Children's Health Research Institute, LLC ( Site 0024)	Lincoln	Nebraska
United States	Summerwood Pediatrics ( Site 0009)	Liverpool	New York
United States	Suncoast Research Associates, LLC ( Site 0035)	Miami	Florida
United States	Wasatch Pediatrics-Cottonwood Office ( Site 0014)	Murray	Utah
United States	University of Rochester Medical Center ( Site 0029)	Rochester	New York
United States	Multicare ( Site 0019)	Spokane	Washington
United States	Piedmont Healthcare, PA ( Site 0025)	Statesville	North Carolina
United States	SUNY Upstate Medical University ( Site 0008)	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Puerto Rico,  Thailand,  Turkey, 

References & Publications (1)

Bili A, Dobson S, Quinones J, Phongsamart W, Oberdorfer P, Kosalaraksa P, Dagan R, Richmond P, Wilck M, Vallejos W, Nunn C, McFetridge R, Tamms G, Fu R, Lupinacci R, Musey L, Banniettis N, Bickham K; V114-027 PNEU-DIRECTION study group. A phase 3, multice — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Solicited Injection-site Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, the percentage of participants with solicited injection-site AEs was assessed for up to ~14 days after each vaccination. The solicited injection-site AEs assessed were erythema/redness, induration/hard lump, tenderness/pain and swelling.	Up to ~14 days after each vaccination
Primary	Percentage of Participants With a Solicited Systemic AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, the percentage of participants with solicited systemic AEs was assessed for up to ~14 days after each vaccination. The solicited systemic AEs assessed were appetite lost/decreased appetite, irritability, drowsiness/somnolence and hives or welts/urticaria.	Up to ~14 days after each vaccination
Primary	Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE)	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgement. Relatedness of an SAE to the study vaccine was determined by the investigator. Per protocol, the percentage of participants with vaccine-related SAEs was assessed through 6 months following Vaccination 4.	Up to ~6 months after Vaccination 4 (up to ~19 months)
Primary	Geometric Mean Concentration (GMC) of Anti-Pneumococcal Polysaccharide (PnP) Immunoglobulin G (IgG) For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4	The GMC of anti-PnP serotype-specific IgG for 13 shared serotypes contained in V114 and Prevnar 13™ (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) was assessed using a pneumococcal electrochemiluminescence (PnECL) assay. Per protocol, 13 IgG serotypes in Groups 2, 3, 4 (experimental arms) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4 as a pre-specified primary outcome analysis; 13 IgG serotypes in Group 5 (experimental arm) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4, as a separate protocol-specified secondary outcome analysis and reported later in the record.	30 Days after Vaccination 4 (Months 11-14)
Secondary	Group 5 Versus Group 1 + Group 2: Percentage of Participants With Anti-Hepatitis B Surface Antigen (HBsAg) =10 mIU/mL at 30 Days Post Vaccination 3	The concentration of anti-HBsAg was assessed using an enhanced chemiluminescence assay. The protocol-specified analysis of the percentage of participants with anti-HBsAg =10 mIU/mL at 30 days post vaccination 3 was conducted in participants combined across vaccine dosing schedules (Group 1 + Group 2) as well as in participants separated across vaccine dosing schedules (Group 1, Group 2). Per protocol, participants with anti-HBsAg =10 mIU/mL in Group 5 were compared to Group 1 + Group 2 at 30 days post Vaccination 3, as a pre-specified secondary outcome analysis. Analysis of participants with anti-HBsAg =10 mIU/mL was not planned to be reported in Group 3 and Group 4, per protocol.	30 Days after Vaccination 3 (Month 5)
Secondary	Group 5 Versus Group 1 + Group 2: Geometric Mean Titer (GMT) of Anti-Rotavirus Immunoglobulin A (IgA) at 30 Days Post Vaccination 3	The GMT of anti-rotavirus IgA was assessed using a serum IgA enzyme linked immunosorbent assay. The protocol specified analysis of anti-rotavirus IgA GMT at 30 days post vaccination 3 was conducted in participants combined across vaccine dosing schedules (Group 1 + Group 2) as well as in participants separated across vaccine dosing schedules (Group 1, Group 2). Per protocol, GMT of anti-rotavirus IgA in Group 5 was compared to Group 1 + Group 2 at 30 days post Vaccination 3, as a pre-specified secondary outcome analysis. Anti-rotavirus IgA GMT analysis was not planned to be reported in Group 3 and Group 4, per protocol.	30 Days after Vaccination 3 (Month 5)
Secondary	GMC of Anti-PnP IgG for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3	The concentration of anti-PnP serotype-specific IgG for 15 serotypes contained in V114 (13 serotypes shared with Prevnar 13™ [1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F] and 2 unique serotypes [22F, 33F]) was assessed using a PnECL assay. Per protocol, GMC of 15 IgG serotypes was assessed at 30 days post Vaccination 3.	30 Days after Vaccination 3 (Month 5)
Secondary	Percentage of Participants With Anti-PnP IgG Concentration =0.35 µg/mL for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3	The concentration of anti-PnP serotype-specific IgG for 15 serotypes contained in V114 (13 serotypes shared with Prevnar 13™ [1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F] and 2 unique serotypes [22F, 33F]) was assessed using a PnECL assay. Per protocol, percentage of participants with anti-PnP IgG concentrations =0.35 µg/mL was assessed at 30 days post Vaccination 3.	30 Days after Vaccination 3 (Month 5)
Secondary	Group 5 Versus Group 1: GMC of Anti-PnP IgG For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4	The GMC of anti-PnP serotype-specific IgG for 13 shared serotypes contained in V114 and Prevnar 13™ (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) was assessed using a PnECL assay. Per protocol, GMC of 13 IgG serotypes was analysed by vaccine dosing schedules (Groups 1, 5). Per protocol, 13 IgG serotypes in Group 5 (experimental arm) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4 as a pre-specified secondary outcome analysis; 13 IgG serotypes in Groups 2, 3, 4 (experimental arms) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4, as a separate protocol-specified primary outcome analysis and reported earlier in the record.	30 Days after Vaccination 4 (Months 11-14)