Phase III, Randomized, Single-blind, Placebo-controlled, Multi-center Study to Evaluate Non-interference of Concomitant Administration of Routine Pediatric Vaccines on the Antibody Response of an Investigational Live-attenuated Respiratory Syncytial Virus (RSV) Vaccine in Healthy Infants and Toddlers (CORAL)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2,226
- 试验地点
- 72
- 主要终点
- RSV B serum neutralizing antibody titers at 28 days post dose 2 (D85) Groups 1 and 3
研究概览
简要总结
This study is a Phase III, randomized, single-blind, placebo-controlled, multi-center study to be conducted in healthy infants and toddlers which will be enrolled at approximately 6 months of age (Cohort 1) and approximately 12 months of age (Cohort 2). The primary objective of the study will be to assess non-inferiority of the RSV infant and toddler (RSVt) vaccine antibody response when administered concomitantly with routine pediatric vaccines at 6 months of age (Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus b Conjugate and Hepatitis B Vaccine [Vaxelis® or Pentacel® and Recombivax HB®] Prevnar 20®, and RotaTeq®), and 12 months of age (M-M-R II, VARIVAX, and Prevnar 20 or per local country recommendations) compared to when administered non-concomitantly.
详细描述
The study duration is approximately 9 months for each participant.
- Cohort 1: Visits at 6, 7, and 8 and 9 months of age for both groups with visit at 10 months of age for Group 2 only
- Cohort 2: Visits at 12, 13, 14 and 15 months of age for both groups with visit at 16 months of age for Group 4 only
- Routine pediatric vaccines (authorized auxiliary medicinal products (AxMP) will be administered at 6 months in Cohort 1 and 12 months of age in Cohort 2, as per Advisory Committee on Immunization Practice (ACIP) or local country recommendations.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
- Blinding for vaccine group assignment: participants, parents or legally acceptable representatives (LAR) and laboratory personnel at the Sponsor
- No blinding for study staff who prepare and administer the study interventions, investigators or Sponsor study staff
入排标准
- 年龄范围
- 6 Months 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 6 months for Cohort 1 and 12 months for Cohort 2 on the day of inclusion ("6 months" means from the day of the 6-month birthday to the day before the 7-month birthday and "12 months" means from the day of the 12-month birthday to the day before the 13-month birthday)
- •Participants who are healthy as determined by medical evaluation including medical history and physical examination
- •For Cohort 1: Infant received doses of vaccines containing hepatitis B, diphtheria, tetanus, pertussis, Haemophilus influenzae type B (Hib), and inactivated poliovirus vaccine (IPV) antigens, with Advisory Committee on Immunization Practice (ACIP) recommended vaccines. The last dose(s) of these vaccines must be at least 28 days before the first study visit
- •Infant received the recommended doses of a recommended pneumococcal conjugate vaccine (as per local schedule) at least 28 days before the first study visit.
排除标准
- •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)
- •Known previous infection with diphtheria, tetanus, Hib, measles, mumps, rubella, rotavirus, pneumococcus, polio, hepatitis B virus
- •Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention used in the study or to a product containing any of the same substances
- •Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
- •History of medically diagnosed wheezing
- •Any acute febrile illness in the past 48 hours that according to investigator judgment is significant enough to interfere with successful inoculation on the day of vaccination. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
- •Probable or confirmed ongoing case of viral respiratory infection (including COVID 19, influenza, rhinovirus, etc.) at the time of enrollment. A prospective participant should not be included in the study until the respiratory infection has resolved.
- •Member of a household that contains an immunocompromised individual, including, but not limited to:
- •A person living with human immunodeficiency virus (HIV)
- •A person who has received chemotherapy within the 12 months prior to study enrollment
- •A person who has received (within the past 6 months) or is receiving (at the time of enrollment) immunosuppressant agents
- •A person living with a solid organ or bone marrow transplant
- •Potential close contact with other immunocompromised individual within 30 days after each vaccination as per investigator's discretion
- •History of definitive contraindications to any of the concomitant vaccines that will be administered as part of the study protocol
- •Participant's biological mother with previous receipt or planned administration of an investigational RSV vaccine during pregnancy and/or breastfeeding
- •Receipt of any vaccine in the 4 weeks preceding RSVt vaccine administration or planned receipt of any vaccine outside of study protocol in the 4 weeks following RSVt vaccine administration, except for influenza and/or COVID-19 vaccination, which may be received at least 1 week before or 1 week after RSVt vaccine administration
- •Previous receipt of an investigational RSV vaccine or receiving any anti RSV product (such as ribavirin or RSV immune globulin) at the time of enrollment
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months
- •Receipt of intranasal and intra-ocular medications within 3 days prior to study enrollment
- •Previous receipt of an RSV monoclonal antibody within 6 months prior to the first study vaccine administration or planned receipt for duration of the study
- •For Cohort 1: Prior receipt of routine 6-month pediatric vaccine doses (as per local schedule)
- •For Cohort 2: Prior receipt of routine 12-month pediatric vaccine doses (as per local schedule)
- •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
Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age
干预措施: RSVt vaccine (Biological)
Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age
干预措施: Diphtheria, tetanus, pertussis, poliomyelitis , Haemophilus influenzae type b, and hepatitis B vaccine (Biological)
Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age
干预措施: Diphtheria, tetanus, pertussis, Haemophilus influenzae type b and poliomyelitis vaccine (Biological)
Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age
干预措施: Hepatitis B vaccine (Biological)
Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age
干预措施: Streptococcus pneumoniae vaccine (Biological)
Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age
干预措施: Rotavirus vaccine (Biological)
Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age
干预措施: Placebo (Biological)
Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age
干预措施: RSVt vaccine (Biological)
Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age
干预措施: Diphtheria, tetanus, pertussis, poliomyelitis , Haemophilus influenzae type b, and hepatitis B vaccine (Biological)
Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age
干预措施: Diphtheria, tetanus, pertussis, Haemophilus influenzae type b and poliomyelitis vaccine (Biological)
Cohort 2: Group 4- (RSVt vaccine non-concomitantly at 13 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 13 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered concomitantly at 12 months of age
干预措施: Placebo (Biological)
Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age
干预措施: Hepatitis B vaccine (Biological)
Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age
干预措施: Streptococcus pneumoniae vaccine (Biological)
Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age
干预措施: Rotavirus vaccine (Biological)
Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age
干预措施: Placebo (Biological)
Cohort 2: Group 3- (RSVt vaccine concomitantly at 12 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 12 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered non-concomitantly at 13 months of age
干预措施: RSVt vaccine (Biological)
Cohort 2: Group 3- (RSVt vaccine concomitantly at 12 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 12 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered non-concomitantly at 13 months of age
干预措施: Streptococcus pneumoniae vaccine (Biological)
Cohort 2: Group 3- (RSVt vaccine concomitantly at 12 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 12 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered non-concomitantly at 13 months of age
干预措施: Measles, mumps, and rubella vaccine (Biological)
Cohort 2: Group 3- (RSVt vaccine concomitantly at 12 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 12 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered non-concomitantly at 13 months of age
干预措施: Varicella virus vaccine (Biological)
Cohort 2: Group 3- (RSVt vaccine concomitantly at 12 months)
Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 12 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered non-concomitantly at 13 months of age
干预措施: Placebo (Biological)
Cohort 2: Group 4- (RSVt vaccine non-concomitantly at 13 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 13 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered concomitantly at 12 months of age
干预措施: RSVt vaccine (Biological)
Cohort 2: Group 4- (RSVt vaccine non-concomitantly at 13 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 13 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered concomitantly at 12 months of age
干预措施: Streptococcus pneumoniae vaccine (Biological)
Cohort 2: Group 4- (RSVt vaccine non-concomitantly at 13 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 13 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered concomitantly at 12 months of age
干预措施: Measles, mumps, and rubella vaccine (Biological)
Cohort 2: Group 4- (RSVt vaccine non-concomitantly at 13 months)
Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 13 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered concomitantly at 12 months of age
干预措施: Varicella virus vaccine (Biological)
结局指标
主要结局
RSV B serum neutralizing antibody titers at 28 days post dose 2 (D85) Groups 1 and 3
时间窗: Day 85
Antibody titers at Day 85
RSV A serum neutralizing antibody titers at 28 days post dose 2 (D85) Groups 1 and 3
时间窗: Day 85
Antibody titers at Day 85
RSV A serum neutralizing antibody titers at Day 113 Groups 2 and 4
时间窗: Day 113
Antibody titers at Day 113
RSV B serum neutralizing antibody titers at Day 113 Groups 2 and 4
时间窗: Day 113
Antibody titers at Day 113
次要结局
- Anti- polyribosylribitol phosphate (PRP) Ab concentrations ≥ 0.15 micrograms per milliliter (µg/mL) Cohort 1(28 days after the 6 month routine vaccinations)
- Anti-rubella Ab concentrations ≥ 10 IU/mL Cohort 2(28 days after the 12 month routine vaccinations)
- Anti- hepatitis B surface antigen (HBsAg) Immunoglobulin g (IgG) antibody (A)b concentrations ≥ 10 milli international units per milliliter (mIU/mL) Cohort 1(28 days after the 6 month routine vaccinations)
- Anti-pertussis Ab concentrations pertussis toxin, filamentous hemagglutinin , pertactin, fimbriae (PT, FHA, PRN, FIM) Cohort 1(28 days after the 6 month routine vaccinations)
- Descriptive: Anti-tetanus Ab concentrations (IU/mL) Cohort 1(28 days after the 6 month routine vaccinations)
- Anti-tetanus Ab concentrations ≥ 0.1 IU/mL Cohort 1(28 days after the 6 month routine vaccinations)
- Anti-mumps Ab concentrations ≥ 10 antibody units (AbU/mL) Cohort 2(28 days after the 12 month routine vaccinations)
- Descriptive: Anti-diphtheria Ab concentrations ≥ 0.01 IU/mL Cohort 1(28 days after the 6 month routine vaccinations)
- Anti-poliovirus types (1, 2, and 3) Ab titers ≥ 1:8 Cohort 1(28 days after the 6 month routine vaccinations)
- Anti-pneumococcal Ab concentrations measured by electrochemiluminescence (ECL) for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F Cohort 1(28 days after the 6 month routine vaccinations)
- Anti-measles Ab concentrations ≥ 255 mIU/mL Cohort 2(28 days after the 12 month routine vaccinations)
- Anti-varicella Ab concentrations ≥ 5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units/mL Cohort 2(28 days after the 12 month routine vaccinations)
- Anti-pneumococcal Ab concentrations measured by ECL Cohort 2(28 days after the 12 month routine vaccinations)
- Descriptive: Anti-measles Ab concentrations (mIU/mL) Cohort 2(28 days after the 12 month routine vaccinations)
- Descriptive: Anti-mumps Ab concentrations (AbU/mL) Cohort 2(28 days after the 12 month routine vaccinations)
- RSV B serum neutralizing antibody titers by baseline serostatus 28 days post-dose 2 Cohort 1 and Cohort 2(28 days post-dose 2)
- Presence of serious adverse events (SAEs) throughout the study Cohort 1 and Cohort 2(Throughout the study, approximately 9 months)
- Anti-diphtheria Ab concentrations ≥ 0.1 IU/mL Cohort 1(28 days after the 6 month routine vaccinations)
- Descriptive: Anti-PRP Ab concentrations (µg/mL) Cohort 1(28 days after the 6 month routine vaccinations)
- Descriptive: Anti-diphtheria Ab concentrations (IU/mL) Cohort 1(28 days after the 6 month routine vaccinations)
- Descriptive: Anti-rubella Ab concentrations (IU/mL) Cohort 2(28 days after the 12 month routine vaccinations)
- Presence of solicited administration site reactions within 21 days after each investigational medicinal product (IMP) administration Cohort 1 and Cohort 2(21 days after each IMP administration)
- Presence of unsolicited systemic adverse events (AEs) reported in the 30 minutes after each study intervention administration Cohort 1 and Cohort 2(Within 30 minutes after each study intervention administration)
- Descriptive: Anti-tetanus Ab concentrations ≥ 0.01 IU/mL Cohort 1(28 days after the 6 month routine vaccinations)
- Descriptive: Anti-varicella Ab concentrations (gpELISA units/mL)(28 days after the 12 month routine vaccinations)
- RSV A serum neutralizing antibody titers by baseline serostatus 28 days post-dose 2 1 Cohort 1 and Cohort 2(28 days post-dose 2)
- Descriptive: Anti-HBsAg Ab concentrations (mIU/mL) Cohort 1(28 days after the 6 month routine vaccinations)
- Descriptive: Anti-HBsAg Ab concentrations ≥ 100 mIU/mL Cohort 1(28 days after the 6 month routine vaccinations)
- Descriptive: Anti-poliovirus types (1, 2, and 3) Ab titers Cohort 1(28 days after the 6 month routine vaccinations)
- Presence of solicited systemic reactions within 21 days after each IMP administration Cohort 1 and Cohort 2(21 days after each IMP administration)
- Presence of adverse events of special interest (AESIs) throughout the study Cohort 1 and Cohort 2(Throughout the study, approximately 9 months)
- RSV A serum neutralizing antibody titers by baseline serostatus at Day 1 Cohort 1 and Cohort 2(Day 1)
- RSV B serum neutralizing antibody titers by baseline serostatus at Day 1 Cohort 1 and Cohort 2(Day 1)
- Presence of unsolicited AEs within 28 days after each study intervention administration Cohort 1 and Cohort 2(Within 28 days after each study intervention administration)
- Presence of medically attended adverse events (MAAEs) throughout the study Cohort 1 and Cohort 2(Throughout the study, approximately 9 months)