A Phase 3, Randomized, Modified Double-blind, Active-controlled, Parallel-group, 2-arm Study to Investigate the Safety and Immunogenicity of a 4-dose Regimen of a 21-valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,714
- 试验地点
- 211
- 主要终点
- Seroresponse rate for PCV21 serotypes
研究概览
简要总结
This study is a Phase 3, randomized, modified double-blind study which aims to measure whether PCV21 vaccine (investigational pneumococcal conjugate vaccine) is safe and can help the body to develop germ-fighting agents called "antibodies" (immunogenicity) compared with 20-valent pneumococcal vaccine (Prevnar 20, licensed pneumococcal conjugate vaccine) when they are administered with routine pediatric vaccines in infants aged from approximately 2 months (42 to 89 days).
The study duration per participant will be up to approximately 19 months. The study vaccines (either PCV21 or 20-valent pneumococcal vaccines) will be administered at approximately 2, 4, 6 and 12 to 15 months of age. Routine pediatric vaccines will be given at the same timepoints.
There will be 6 study visits:
-Visit (V)01, V02 separated from V01 by 60 days, V03 separated from V02 by 60 days, V04 separated from V03 by 30 days, V05 at 12 months of age until 15 months of age, V06 separated from V05 by 30 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Modified double-blind
- Blinding for vaccine group assignment: participants and participant's parent(s) / legally acceptable representative(s) (LARs), outcome assessors, Investigators, laboratory personnel, and Sponsor study staff
- No blinding for vaccine group assignment: those preparing and administering the study interventions
入排标准
- 年龄范围
- 42 Days 至 89 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 42 to 89 days on the day of inclusion
- •Participants who are healthy as determined by medical evaluation including medical history and physical examination
- •Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg or born after a gestation period above 28 (> 28 weeks) through 36 weeks with a birth weight ≥ 1.5 kg, and in both cases medically stable as assessed by the investigator
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •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
- •History of microbiologically confirmed Streptococcus pneumoniae infection or disease
- •Any contraindication to the routine pediatric vaccines being administered in the study
- •History of seizure or significant stable or progressive neurological disorders such as infantile spasms, inflammatory nervous system diseases, encephalopathy, cerebral palsy
- •Known systemic hypersensitivity to any of the study interventions components, or history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances
- •Laboratory-confirmed or known thrombocytopenia, as reported by the parent/legally acceptable representative (LAR), contraindicating intramuscular (IM) injection
- •Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM injection
- •Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
- •Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
- •Receipt of any vaccine in the 4 weeks preceding the study intervention administration or planned receipt of any vaccine in the 4 weeks following the study intervention administration, except for US licensed 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, as applicable per local recommendations.
- •Previous vaccination against S. pneumoniae
- •Previous vaccination against the following antigens: diphtheria, tetanus, pertussis, Haemophilus influenzae type b, and poliovirus
- •Receipt of more than 1 dose of hepatitis B vaccine
- •Receipt of immune globulins, blood or blood-derived products since birth
- •Participation at the time of study enrollment (or in the 6 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
- •Note: The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
研究组 & 干预措施
Group 1: PCV21
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of PCV21 at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of PCV21 will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: RotaTeq (Biological)
Group 1: PCV21
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of PCV21 at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of PCV21 will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: Hexaxim Vaccine (Biological)
Group 2: 20vPCV
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of 20vPCV at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of 20vPCV will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: RotaTeq (Biological)
Group 2: 20vPCV
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of 20vPCV at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of 20vPCV will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: Varivax (Biological)
Group 2: 20vPCV
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of 20vPCV at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of 20vPCV will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: Hexaxim Vaccine (Biological)
Group 2: 20vPCV
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of 20vPCV at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of 20vPCV will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: Prevnar 20 vaccine (Biological)
Group 2: 20vPCV
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of 20vPCV at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of 20vPCV will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: M-M-R II vaccine (Biological)
Group 2: 20vPCV
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of 20vPCV at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of 20vPCV will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: Vaxelis vaccine (Biological)
Group 1: PCV21
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of PCV21 at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of PCV21 will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: Vaxelis vaccine (Biological)
Group 1: PCV21
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of PCV21 at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of PCV21 will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: Varivax (Biological)
Group 1: PCV21
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of PCV21 at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of PCV21 will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: PCV21 vaccine (Biological)
Group 1: PCV21
Participants will be administered via intramuscular injection (IM) a 3-dose primary series of PCV21 at approximately 2, 4 and 6 months of age (MoA) co- administered with Vaxelis or Hexaxim (for participants included in South Korea only) and RotaTeq. At toddler age (12 to 15 MoA), a 4th dose of PCV21 will be administered concomitantly with a single dose of M-M-M-R II and Varivax.
干预措施: M-M-R II vaccine (Biological)
结局指标
主要结局
Seroresponse rate for PCV21 serotypes
时间窗: 30 days post-dose 3
Serotype specific IgG concentration ≥ 0.35 µg/mL
IgG concentration for PCV21 serotypes
时间窗: 30 days post-dose 4
Serotype specific IgG GMC post-dose 4
IgG concentration for PCV21 serotypes
时间窗: 30 days post-dose 3
Serotype specific IgG Geometric Mean Concentration (GMC)
次要结局
- Anti- hepatitis B surface antigen (HBsAg) Ab(30 days post-dose 3)
- Anti- polyribosylribitol phosphate (PRP) Ab(30 days post-dose 3)
- Anti-poliovirus types (1, 2, and 3) Ab(30 days post-dose 3)
- Anti-diphtheria Ab concentrations(30 days post-dose 3)
- Anti-tetanus Ab concentrations(30 days post-dose 3)
- Anti-pertussis Ab concentrations (Pertussis toxin (PT) and Filamentous Hemagglutinin (FHA))(30 days post-dose 3)
- Anti-rotavirus serum immunoglobulin A (IgA) Ab concentrations(30 days post-dose 3)
- Anti-varicella Ab concentrations(30 days post-dose 4)
- IgG concentration for the additional serotype 9N(30 days post-dose 3)
- IgG concentration for serotype 3(30 days post-dose 4)
- IgG concentration for additional serotype 9N(30 days post-dose 4)
- Serotype specific OPA titers for all serotypes included in PCV21(Before dose 4 and 30 days post-dose 4)
- Presence of any immediate adverse events (AEs)(Within 30 minutes after each vaccine injection)
- Presence of serious adverse events (SAEs) throughout the study (through 6 months post- last vaccine injection)(Throughout the study (through 6 months post-last vaccine injection), approximately 20 months)
- Serotype 9N specific IgG GMC post-dose 4(30 days post-dose 4)
- Presence of solicited injection site and systemic reactions through 7 days after each vaccine injection(Through 7 days after each vaccine injection)
- Presence of unsolicited (spontaneously reported) injection site reactions and unsolicited systemic AEs through 30 days after each vaccine injection(Through 30 days after each vaccine injection)
- Seroresponse rate for PCV21 serotypes(30 days post-dose 4)
- IgG concentration for PCV21 serotypes(Before dose 4 and 30 days post-dose 4)
- Serotype specific OPA titers ≥ lower limit of quantitation (LLOQ) for all serotypes included in PCV21(Before dose 4 and 30 days post-dose 4)
- IgG concentration for serotype 3(30 days post-dose 3)
- IgG concentration for additional serotype 9N(30 days post-dose 3)
- Serotype specific OPA titers for all serotypes included in PCV21(30 days post-dose 3)
- Serotype specific OPA titers ≥ lower limit of quantitation (LLOQ) for all serotypes included in PCV21(30 days post-dose 3)
- Anti-measles Ab concentrations(30 days post-dose 4)
- Anti-mumps Ab concentrations(30 days post-dose 4)
- Anti-rubella Ab concentrations(30 days post-dose 4)