Safety and Immunogenicity of Catch-up Vaccination Regimens of V114 (V114-024)

Pneumococcal Infections Clinical Trial

— PNEU-PLAN  

Official title:

A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of Catch-up Vaccination Regimens of V114 in Healthy Infants, Children, and Adolescents (PNEU-PLAN)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03885934
• Other study ID #: V114-024
• Secondary ID: 2018-003706-88
• Status: Completed
• Phase: Phase 3
• Start date: June 25, 2019
• Est. completion date: December 9, 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 purpose of this study is 1) to evaluate the safety and tolerability of V114 with respect to the proportion of participants with adverse events (AEs) and 2) to evaluate the anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) at 30 days following the last dose for each vaccination group. There is no formal hypothesis testing in this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 606
• Est. completion date: December 9, 2020
• Est. primary completion date: December 9, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 7 Months to 17 Years

Eligibility

Inclusion Criteria

• Not be pregnant or breastfeeding

• Not be a woman of childbearing potential

• If of a woman of childbearing potential, agree to follow the contraceptive guidance during the treatment period and for at least 6 weeks after the last dose of study intervention

• 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

• History of invasive pneumococcal disease (IPD)

• Known hypersensitivity to any component of the PCV or any diphtheria toxoid-containing vaccine

• Had a recent febrile illness occurring within 72 hours prior to receipt of study vaccine

• Known or suspected impairment of immunological function

• History of congenital or acquired immunodeficiency

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

• Known or history of functional or anatomic asplenia

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

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

• Is 7 to 23 months of age and has received a dose of a pneumococcal vaccine prior to study entry based on medical record. Participants =2 years of age could have received a PCV at least 8 weeks prior to study entry as follows: a partial regimen of Prevnar™,Synflorix™, or Prevnar 13™ or a full regimen of Prevnar™ or Synflorix™ based on local guidelines. Participants should not have received any dose of a pneumococcal polysaccharide vaccine

• Meets one or more of the following systemic corticosteroid exclusion criteria: has received systemic corticosteroids (equivalent of =2 mg/kg total daily dose of prednisone or =20 mg/day for persons weighing >10 kg) for =14 consecutive days and has not completed this course of treatment at least 30 days prior to the first dose of study vaccine at randomization; has received or is expected to receive systemic corticosteroids exceeding physiologic replacement doses (approximately 5 mg/day prednisone equivalent) within 14 days prior to any dose of study vaccine; or is expected to require systemic corticosteroids within 30 days after any study vaccination during conduct of the study (Note: Topical, ophthalmic and inhaled steroids are permitted)

• Has received other licensed non-live vaccines within 14 days before receipt of study vaccine. Exception: Inactivated influenza vaccine may be administered but must be given at least 7 days before receipt of study vaccine or at least 15 days after receipt of study vaccine

• Has received a licensed live vaccine within 30 days before receipt of study vaccine

• Has received a blood transfusion or blood products, including immunoglobulins, within 6 months before receipt of study vaccine

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

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

Biological:
• V114
V114 15-valent PCV containing 13 serotypes present in Prevnar 13® (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and 2 unique serotypes (22F and 33F) in each 0.5 mL IM administration
• Prevnar 13®
Prevnar 13® 13-valent PCV containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in each 0.5 mL IM administration.

Locations

Country	Name	City	State
Finland	Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0007)	Espoo
Finland	Tampereen yliopisto Etelä-Helsingin rokotetutkimusklinikka ( Site 0005)	Helsinki
Finland	Tampereen yliopisto Ita-Helsingin rokotetutkimusklinikka ( Site 0006)	Helsinki
Finland	Tampereen yliopisto Järvenpään rokotetutkimusklinikka ( Site 0003)	Jarvenpaa
Finland	Tampereen yliopisto Kokkolan rokotetutkimusklinikka ( Site 0009)	Kokkola
Finland	Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0004)	Oulu
Finland	Tampereen yliopisto Porin rokotetutkimusklinikka ( Site 0008)	Pori
Finland	Seinajoki Vaccine Research Center ( Site 0010)	Seinajoki
Finland	Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0001)	Tampere
Finland	Tampereen yliopisto Turun rokotetutkimusklinikka ( Site 0002)	Turku
Malaysia	Sabah Womens & Childrens Hospital ( Site 0902)	Kota Kinabalu
Malaysia	University Malaya Medical Centre ( Site 0901)	Kuala Lumpur
Poland	Centrum Medyczne Pratia Bydgoszcz ( Site 0210)	Bydgoszcz
Poland	Przychodnia Vitamed Gaaj i Cichomski Spolka Jawna ( Site 0212)	Bydgoszcz
Poland	SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0209)	Lomianki
Poland	Spec Zesp Opieki Zdrowotnej nad Matka i Dzieckiem w Poznaniu ( Site 0213)	Poznan
Poland	NZ Lecznictwa Ambulatoryjnego - Michalkowice - Jarosz i Partnerzy ( Site 0211)	Siemianowice Slaskie
Poland	Uniwersytecki Szpital Kliniczny ( Site 0207)	Wroclaw
Russian Federation	MAI Childrens City Clinical Hospital 11 ( Site 0305)	Ekaterinburg
Russian Federation	Central Clinical Hospital of Russian Academy Science ( Site 0317)	Moscow
Russian Federation	Research Institute of Children Infections ( Site 0301)	Saint Petersburg
Russian Federation	Children s City Polyclinic No. 45 of the Nevsky District ( Site 0312)	St.Petersburg
Thailand	Chulalongkorn University ( Site 0601)	Bangkok
Thailand	Siriraj Hospital ( Site 0600)	Bangkok
Thailand	Vaccine Trial Center Faculty of Tropical Medicine ( Site 0603)	Bangkok
Thailand	Srinagarind Hospital ( Site 0602)	Khonkaen

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

Finland,  Malaysia,  Poland,  Russian Federation,  Thailand, 

References & Publications (1)

Banniettis N, Wysocki J, Szenborn L, Phongsamart W, Pitisuttithum P, Ramet M, Richmond P, Shi Y, Dagan R, Good L, Papa M, Lupinacci R, McFetridge R, Tamms G, Churchill C, Musey L, Bickham K; V114-024 PNEU-PLAN study group. A phase III, multicenter, random — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Concentration of Serotype-specific Immunoglobulin G - Schedule A: 7-11 Months	The geometric mean concentration (GMC) of immunoglobulin G (IgG) serotype-specific antibodies to the 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 was determined. Sera from participants was used to measure vaccine-induced anti-pneumococcal polysaccharides (PnPs) serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL) assay. The within-group 95% confidence intervals (CIs) were derived by exponentiating the CIs of the mean of the natural log values based on the t-distribution.	30 days post last vaccination
Primary	GMC of Serotype-specific IgG - Schedule B: 12-23 Months	The GMC of IgG serotype-specific antibodies to the 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 was determined. Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL) assay. The within-group 95% CIs were derived by exponentiating the CIs of the mean of the natural log values based on the t-distribution.	30 days post last vaccination
Primary	GMC of Serotype-specific IgG - Schedule C: 2-17 Years	The GMC of IgG serotype-specific antibodies to the 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 was determined. Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL) assay. The within-group 95% CIs were derived by exponentiating the CIs of the mean of the natural log values based on the t-distribution.	30 days post vaccination
Primary	Percentage of Participants With Solicited Injection-site Adverse Events - Schedule A: 7-11 Months	An adverse event (AE) is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 14 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (redness/erythema, hardness/induration, swelling, and pain) was summarized.	Up to 14 days post any vaccination
Primary	Percentage of Participants With Solicited Injection-site AEs - Schedule B: 12-23 Months	An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 14 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (redness/erythema, hardness/induration, swelling, and pain) was summarized.	Up to 14 days post any vaccination
Primary	Percentage of Participants With Solicited Injection-site AEs - Schedule C: 2-17 Years	An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 14 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (redness/erythema, hardness/induration, swelling, and pain) was summarized.	Up to 14 days post vaccination
Primary	Percentage of Participants With Solicited Systemic AEs - Schedule A: 7-11 Months	An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any VRC-prompted systemic AEs that occurred in the 14 days after any vaccination. For participants 7 months to <3 years of age at enrollment, solicited systemic AEs include irritability, drowsiness/somnolence, appetite lost/decreased appetite, and hives or welts/urticaria. The percentage of participants with a systemic AE was summarized.	Up to 14 days post any vaccination
Primary	Percentage of Participants With Solicited Systemic AEs - Schedule B: 12-23 Months	An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any VRC-prompted systemic AEs that occurred in the 14 days after any vaccination. For participants 7 months to <3 years of age at enrollment, solicited systemic AEs include irritability, drowsiness/somnolence, appetite lost/decreased appetite, and hives or welts/urticaria. The percentage of participants with a systemic AE was summarized.	Up to 14 days post any vaccination
Primary	Percentage of Participants With Solicited Systemic AEs - Schedule C: 2-17 Years	An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any VRC-prompted systemic AEs that occurred in the 14 days after any vaccination. For participants 7 months to <3 years of age at enrollment, solicited systemic AEs include irritability, drowsiness/somnolence, appetite lost/decreased appetite, and hives or welts/urticaria. For participants =3 years of age at enrollment, solicited systemic AEs include muscle pain/ myalgia, joint pain/arthralgia, headache, tiredness/fatigue, and hives or welts/urticaria. The percentage of participants with a systemic AE was summarized.	Up to 14 days post vaccination
Primary	Percentage of Participants With at Least 1 Vaccine-related Serious Adverse Event - Schedule A: 7-11 Months	A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that are reported to be at least possibly related by the investigator to study vaccination will be summarized. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.	Up to ~6 months post final vaccination
Primary	Percentage of Participants With at Least 1 Vaccine-related SAE - Schedule B: 12-23 Months	A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that are reported to be at least possibly related by the investigator to study vaccination will be summarized. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.	Up to ~6 months post final vaccination
Primary	Percentage of Participants With at Least 1 Vaccine-related SAE - Schedule C: 2-17 Years	A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that are reported to be at least possibly related by the investigator to study vaccination will be summarized.	Up to ~6 months post vaccination
Secondary	Percentage of Participants Meeting Serotype-specific IgG Threshold Value of =0.35 µg/mL for Each of the 15 Serotypes - Schedule A: 7-11 Months	Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL assay. The percentage that achieved the IgG threshold value of =0.35 µg/mL was summarized. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.	30 days post final vaccination
Secondary	Percentage of Participants Meeting Serotype-specific IgG Threshold Value of =0.35 µg/mL for Each of the 15 Serotypes - Schedule B: 12-23 Months	Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL assay. The percentage that achieved the IgG threshold value of =0.35 µg/mL was summarized. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan. The analysis population included all randomized participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint.	30 days post final vaccination
Secondary	Percentage of Participants Meeting Serotype-specific IgG Threshold Value of =0.35 µg/mL for Each of the 15 Serotypes - Schedule C: 2-17 Years	Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL assay. The percentage that achieved the IgG threshold value of =0.35 µg/mL was summarized. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.	30 days post vaccination