Study of a Pneumococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Toddlers and Infants

Diphtheria Immunisation Clinical Trial

Official title:

Safety and Immunogenicity of a Pneumococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Toddlers and Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04398706
• Other study ID #: PSK00008
• Secondary ID: U1111-1238-1638P
• Status: Completed
• Phase: Phase 2
• Start date: May 22, 2020
• Est. completion date: August 10, 2023

Study information

• Verified date: November 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary objectives:

• To assess the safety profile of each SP0202 formulation and Prevnar 13 in toddlers and infants (after each and any injection).

• To assess the immune response (serotype specific IgG concentration) of the SP0202 formulations and Prevnar 13 1 month after the administration of one dose in toddlers (Groups 1-4)

• To assess the immune response (serotype specific IgG concentration) of the SP0202 formulations and Prevnar 13 1 month after the administration of 3 doses in infants (Groups 5-8)

• To assess the immune response (serotype specific IgG concentration) of the SP0202 formulations and Prevnar 13 1 month after administration of a 4-dose schedule in infants (Groups 5-8)

Secondary objectives:

• To assess the immune response (serotype specific OPA titer) of the SP0202 formulations and Prevnar 13 1 month after the administration of one dose in toddlers (Groups 1-4)

• To assess the immune response (serotype specific OPA titer) of the SP0202 formulations and Prevnar 13 1 month after the administration of 3 doses in a subset of infants (Groups 5-8)

• To assess the immune response (serotype specific OPA titer) of the SP0202 formulations and Prevnar 13 1 month after administration of a 4-dose schedule in a subset of infants (Groups 5-8)

• In toddlers: to describe the Ab responses against Pentacel antigens before and 1 month following injection of Pentacel

• In infants: to describe the Ab responses against antigens of the routine pediatric vaccines (Pentacel, RotaTeq, ENGERIX-B, M-M-RII, and VARIVAX) when administered concomitantly with either SP0202 or Prevnar 13 (at pre-Dose 1 (as applicable) for RotaTeq, Diphteria, Tetanus and Pertussis antigens; at PD3 for ENGERIX-B, RotaTeq, and Pentacel; at PD4 for M-M-RII and VARIVAX])

Description:

For toddlers, the duration of each participant's participation in the study will be approximately 6 months for subjects enrolled in Groups 1, 2, 3, and 4.

For infants, the duration of each participant's participation in the study will be approximately 16 to 19 months for subjects enrolled in Groups 5, 6, 7, and 8.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 853
• Est. completion date: August 10, 2023
• Est. primary completion date: August 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 42 Days to 15 Months

Eligibility

Inclusion criteria :

Toddlers and infants:

• Participant and parent/guardian are able to attend all scheduled visits and to comply with all study procedures

• Born at full term of pregnancy (= 37 weeks) and/or with a birth weight = 5.5 lbs or 2.5 kg

Specifically for toddlers:

• Aged 12 to 15 months on the day of the first study visit

• Participant has received 3 doses of Prevnar 13 and 3 doses of diphteria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b antigens in infancy

Specifically for infants:

• Aged 42 to 89 days on the day of the first study visit

Exclusion criteria:

Toddlers and infants

• Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure

• Family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated

• Blood dyscrasias, leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems

• Active tuberculosis

• History of S. pneumoniae infection or disease, confirmed either serologically or microbiologically

• History of any neurologic disorder, including any seizures and progressive neurologic disorders

• History of Guillain-Barré syndrome

• Known systemic hypersensitivity to any of the vaccine components or to latex, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances

• Verbal report of thrombocytopenia contraindicating intramuscular vaccination in the Investigator's opinion

• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion

• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw

• Chronic illness (including, but not limited to, cardiac disorders, congenital heart disease, chronic lung disease, renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and know congenital or genetic diseases) that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion

• Any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives

• In an emergency setting, or hospitalized involuntarily

• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature = 38.0 C / = 100.4 F). A prospective participant should not be included in the study until the condition has resolved or until 3 days after the febrile event has resolved

• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study Specifically for toddlers

• Receipt of any vaccine in the 4 weeks preceding the study vaccination or planned receipt of any vaccine from enrollment through the last blood sampling Visit (Visit 2), except for influenza vaccination, which may be received at least 2 weeks before or 2 weeks after any study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines

• Receipt of immune globulins, blood or blood-derived products in the past 3 months

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)

• History of diphtheria, tetanus, pertussis, poliomyelitis, and/or H. influenzae type b infection or disease Specifically for infants

• Receipt of any vaccine in the 4 weeks preceding the study vaccination or planned receipt of any vaccine from enrollment through the last blood sampling Visit (Visit 6), except for influenza vaccination or COVID-19 vaccination, which may be received at least 2 weeks before or 2 weeks after any study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines, and COVID-19 vaccines as applicable per local recommendations

• Receipt of immune globulins, blood or blood-derived products since birth.

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) since birth

• Previous vaccination against S. pneumoniae

• Previous vaccination against the following antigens: diphteria, tetanus, pertussis, H. influenzae type b, poliovirus, rotavirus, measles, mumps, rubella, and varicella

• Receipt of more than 1 previous dose of hepatitis B vaccine

• History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, measles, mumps, rubella, varicella, H. influenzae type b, and/or rotavirus infection or disease

• History of intussusception

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Diphtheria
• Diphtheria Immunisation
• Haemophilus Influenzae Type b Immunisation
• Hepatitis B
• Hepatitis B Immunisation
• Measles Immunisation
• Mumps Immunisation
• Pertussis Immunisation
• Pneumococcal Immunisation
• Polio Immunisation
• Rubella
• Rubella Immunisation
• Tetanus Immunisation
• Varicella Immunisation

Intervention

Biological:
• Pneumococcal Conjugate Vaccine formulation 1
Pharmaceutical form:liquid Route of administration: intramuscular
• Pneumococcal Conjugate Vaccine formulation 2
Pharmaceutical form:liquid Route of administration: intramuscular
• Pneumococcal Conjugate Vaccine formulation 3
Pharmaceutical form:liquid Route of administration: intramuscular
• Varicella Virus Vaccine Live
Pharmaceutical form:liquid Route of administration: subcutaneous
• Measles, Mumps, and Rubella Virus Vaccine Live
Pharmaceutical form:liquid Route of administration: subcutaneous
• Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]
Pharmaceutical form:liquid Route of administration: intramuscular
• Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate)
Pharmaceutical form:liquid Route of administration: intramuscular
• Rotavirus Vaccine, Live, Oral, Pentavalent
Pharmaceutical form:liquid Route of administration: oral
• Hepatitis B Vaccine* [Recombinant] *as applicable
Pharmaceutical form:liquid Route of administration: intramuscular

Locations

Country	Name	City	State
Canada	Investigational Site Number : 1240001	Halifax	Nova Scotia
Canada	Investigational Site Number : 1240006	Hamilton	Ontario
Canada	Investigational Site Number : 1240002	Vancouver	British Columbia
Honduras	Investigational Site Number : 3400002	Municipio Del Distrito Central
Honduras	Investigational Site Number : 3400001	San Pedro Sula
Puerto Rico	Investigational Site Number : 6300002	Bayamón
Puerto Rico	Investigational Site Number : 6300004	Guayama
Puerto Rico	Investigational Site Number : 6300001	San Juan
United States	Javara Albany Site Number : 8400140	Albany	Georgia
United States	Javara Annapolis Site Number : 8400137	Annapolis	Maryland
United States	Meridian Clinical Research, LLC Site Number : 8400112	Baton Rouge	Louisiana
United States	Southland Clinical Research Center Site Number : 8400040	Bellflower	California
United States	Bingham Memorial Hospital Site Number : 8400067	Blackfoot	Idaho
United States	Qualmedica Research, LLC Site Number : 8400084	Bowling Green	Kentucky
United States	Atrium Health Site Number : 8400124	Charlotte	North Carolina
United States	Cheraw Pediatrics Site Number : 8400017	Cheraw	South Carolina
United States	Javara Chevy Chase Site Number : 8400138	Chevy Chase	Maryland
United States	Pediatric Associates of Mt. Carmel Site Number : 8400005	Cincinnati	Ohio
United States	Centricity Research Talbotton - DBA IACT Health Research at Talbotton Site Number : 8400062	Columbus	Georgia
United States	Benchmark Research Site Number : 8400012	Covington	Louisiana
United States	Javara Dallas Site Number : 8400135	Dallas	Texas
United States	International Research Partners, LLC Site Number : 8400077	Doral	Florida
United States	Pininos Pediatric Services Site Number : 8400121	El Paso	Texas
United States	Javara Fayetteville Site Number : 8400139	Fayetteville	Georgia
United States	North Texas Clinical Trials Site Number : 8400015	Fort Worth	Texas
United States	Meridian Clinical Research Site Number : 8400102	Grand Island	Nebraska
United States	Tribe Clinical Research Site Number : 8400025	Greenville	South Carolina
United States	Homestead Medical Clinic, P.A. Site Number : 8400032	Homestead	Florida
United States	Houston Clinical Research Associates Site Number : 8400023	Houston	Texas
United States	Joint Clinical Trials Huntington Park Site Number : 8400030	Huntington Park	California
United States	Matrix Clinical Research Huntington Park Site Number : 8400058	Huntington Park	California
United States	Hutchinson Clinic Site Number : 8400074	Hutchinson	Kansas
United States	Leavitt Clinical Research Site Number : 8400127	Idaho Falls	Idaho
United States	The Children's Clinic Of Jonesboro PA Site Number : 8400143	Jonesboro	Arkansas
United States	Children's Mercy Hospital Site Number : 8400008	Kansas City	Missouri
United States	Velocity Clinical Research Lafayette Site Number : 8400132	Lafayette	Louisiana
United States	FMC Science, LLC Site Number : 8400086	Lampasas	Texas
United States	Michael W. Simon, MD, PSC Site Number : 8400002	Lexington	Kentucky
United States	Lincoln Pediatric Group Site Number : 8400125	Lincoln	Nebraska
United States	DCOL Center for Clinical Research Site Number : 8400107	Longview	Texas
United States	Matrix Clinical Research Site Number : 8400059	Los Angeles	California
United States	Biopharma Informatic Site Number : 8400066	McAllen	Texas
United States	Amber Clinical Research, LLC Site Number : 8400019	Miami	Florida
United States	Dade Research Center Site Number : 8400122	Miami	Florida
United States	Miami Clinical Research Site Number : 8400020	Miami	Florida
United States	Boeson Research Site Number : 8400004	Missoula	Montana
United States	Pediatric Infectious Diseases Research Site Number : 8400104	Omaha	Nebraska
United States	Orange County Research Institute Site Number : 8400060	Ontario	California
United States	Benchmark Research San Antonio Site Number : 8400129	San Antonio	Texas
United States	Sun Research Institute Site Number : 8400011	San Antonio	Texas
United States	Tekton Research Site Number : 8400076	San Antonio	Texas
United States	California Research Foundation Site Number : 8400052	San Diego	California
United States	Dumog Research Site Number : 8400134	Smyrna	Georgia
United States	MultiCare Institute for Research & Innovation Site Number : 8400024	Spokane	Washington
United States	Jedidiah Clinical Research Site Number : 8400049	Tampa	Florida
United States	Meridian Clinical Research Washington DC Site Number : 8400119	Washington	District of Columbia
United States	Ardmore Medical Research Site Number : 8400043	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

United States,  Canada,  Honduras,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants reporting immediate adverse events (AEs)	Unsolicited (spontaneously reported) systemic AEs after each and any injection of a SP0202 formulation or Prevnar 13	Within 30 minutes post-vaccination
Primary	Number of participants reporting solicited injection site and systemic reactions	Solicited injection site reactions: tenderness, erythema, swelling Solicited systematic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost and irritability	Up to Day 7 post-vaccination
Primary	Number of participants reporting unsolicited (spontaneously reported) AEs	Unsolicited AEs (events not solicited) after each and any injection of a SP0202 formulation or Prevnar 13	Within 30 days after vaccination
Primary	Number of participants reporting serious adverse events (SAEs) and adverse events of special interest (AESIs)	SAEs and AESIs are collected throughout the study period	From Day 0 to Day 480
Primary	Geometric Mean Concentrations (GMCs) of antibodies against all pneumococcal serotypes included in the SP0202 formulations in toddlers	Ab concentrations for each pneumococcal serotype included in the SP0202 formulations are measured	Day 30
Primary	GMCR of antibodies against all pneumococcal serotypes included in the SP0202 formulations in toddlers	Ab concentrations for each pneumococcal serotype included in the SP0202 formulations are measured The calculated ratio is (post-/pre-vaccination)	Day 30
Primary	Number of infants with serotype-specific IgG concentration above predefined thresholds for each pneumococcal serotype included in the SP0202 formulations	Ab concentrations for each pneumococcal serotype included in the SP0202 formulations are measured The following threshold values will be considered: = 0.35 µg/mL	Day 150
Primary	GMCs of antibodies against all pneumococcal serotypes included in the SP0202 formulations in infants	Ab concentrations for each pneumococcal serotype included in the SP0202 formulations are measured	Day 330
Primary	GMCR of antibodies against all pneumococcal serotypes included in the SP0202 formulations in infants* *as applicable	Ab concentrations for each pneumococcal serotype included in the SP0202 formulations are measured The calculated ratio is (post- dose 3/pre-dose 1)*; *as applicable	Day 150* *as applicable
Primary	GMCR of antibodies against all pneumococcal serotypes included in the SP0202 formulations in infants	Ab concentrations for each pneumococcal serotype included in the SP0202 formulations are measured The calculated ratio is (post- dose 4/pre-dose 4)	Day 330
Secondary	Geometric mean (GM) of serotype specific opsonophagocytic (OPA) titers for all pneumococcal serotypes included in the SP0202 formulations in toddlers	Serotype specific OPA titers for each pneumococcal serotype included in the SP0202 formulations are determined	Day 30
Secondary	Number of toddlers with serotype-specific OPA titers above predefined thresholds for each pneumococcal serotype included in the SP0202 formulations	Serotype specific OPA titers for each pneumococcal serotype included in the SP0202 formulations are determined The following threshold values will be considered: = lower limit of quantitation (LLOQ)	Day 30
Secondary	GM of serotype specific OPA titers ratio for each pneumococcal serotype included in the SP0202 formulations in toddlers	Serotype specific OPA titers for each pneumococcal serotype included in the SP0202 formulations are determined The calculated ratio is (post-/pre-vaccination)	Day 30
Secondary	GM of serotype specific OPA titers for all pneumococcal serotypes included in the SP0202 formulations in infants	Serotype specific OPA titers for each pneumococcal serotype included in the SP0202 formulations are determined	Day 150; Day 300; Day 330
Secondary	Number of infants with serotype specific OPA titers above predefined thresholds for each pneumococcal serotype included in the SP0202 formulations	Serotype specific OPA titers for each pneumococcal serotype included in the SP0202 formulations are determined The following threshold values will be considered: = LLOQ	Day 0; Day 150; Day 300; Day 330
Secondary	GM of serotype specific OPA titers ratio for each pneumococcal serotype included in the SP0202 formulations in infants	Serotype specific OPA titers for each pneumococcal serotype included in the SP0202 formulations are determined The calculated ratio is (post- dose 4/pre-dose 4)	Day 300; Day 330
Secondary	GM concentrations/titers of antibodies against antigens in DTaP-IPV// Hib vaccine when co- administered with SP0202 or Prevnar 13 in toddlers	The following components are assessed : Anti-pertussis (PT, FHA, PRN, FIM) Ab; Anti-PRP Ab; Anti-diphtheria toxoid Ab; Anti-tetanus toxoid Ab; Anti-poliovirus (types 1, 2, and 3) Ab	Day 0
Secondary	GM concentrations/titers of antibodies against antigens in DTaP-IPV// Hib vaccine when DTaP - IPV// Hib vaccine is co- administered with SP0202 or Prevnar 13 in toddlers	The following components are assessed: Anti-PRP Ab; Anti-poliovirus (types 1, 2, 3) Ab; Anti-pertussis (PT, FHA, PRN, FIM) Ab and vaccine response; Anti-diphtheria toxoid Ab; Anti-tetanus toxoid Ab	Day 30
Secondary	Number of toddlers with concentrations/titers of antibodies above predefined thresholds	The following components are assessed, with predefined thresholds for each: Anti-PRP Ab; Anti-poliovirus (types 1, 2, 3) Ab; Anti-pertussis (PT, FHA, PRN, FIM) Ab; Anti-diphtheria toxoid Ab; Anti-tetanus toxoid Ab	Day 30
Secondary	GM concentrations/titers of antibodies against antigens in licensed vaccines when co- administered with SP0202 or Prevnar 13 in infants* *as applicable	The following components are assessed*: Anti-rotavirus serum immunoglobulin (Ig) A Ab; Anti-pertussis (PT, FHA, PRN, and FIM) Ab; Anti-diphtheria toxoid Ab; Anti-tetanus toxoid Ab *as applicable	Day 0* *as applicable
Secondary	GM concentrations/titers of antibodies against antigens in concomitant licensed vaccines when co- administered with SP0202 or Prevnar 13 in infants	The following components are assessed: IgG Abs against hepatitis B surface antigen; Anti-PRP Ab; Anti-poliovirus (types 1, 2, 3) Ab; Anti-rotavirus serum IgA Ab; Anti-pertussis (PT, FHA, PRN, FIM) Ab; Anti-diphtheria toxoid Ab; Anti-tetanus toxoid Ab	Day 150
Secondary	Number of infants with concentrations/titers of antibodies above predefined thresholds	The following components are assessed, with predefined thresholds for each: IgG Abs against hepatitis B surface antigen; Anti-PRP Ab; Anti-poliovirus (types 1, 2, 3) Ab; Anti-rotavirus serum IgA Ab; Anti-pertussis (PT, FHA, PRN, FIM) Ab; Anti-diphtheria toxoid Ab; Anti-tetanus toxoid Ab	Day 150
Secondary	GM concentrations/titers of antibodies against antigens in concomitant licensed vaccines when co- administered with SP0202 or Prevnar 13 in infants	The following components are assessed: Anti-measles Ab; Anti-mumps Ab; Anti-rubella Ab; Anti-varicella Ab	Between Day 330 and Day 420
Secondary	Number of participants with concentrations/titers of antibodies above predefined thresholds	The following components are assessed, with predefined thresholds for each: Anti-measles Ab; Anti-mumps Ab; Anti-rubella Ab; Anti-varicella Ab	Between Day 330 and Day 420