Clinical trial NCT04992260: Efficacy, Immunogenicity and Safety of COVID-19 Vaccine , Inactivated in Children and Adolescents
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled Phase Ⅲ Clinical Trial to Evaluate the Efficacy, Immunogenicity and Safety of COVID-19 Vaccine(Vero Cell) ,Inactivated in Children and Adolescents Aged 6 Months to 17 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Sinovac Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-08-05
Enrollment: 11349
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a global multi-center , case-driven, randomized, double-blinded, and placebo-controlled phase Ⅲ clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research \& Development Co., Ltd. The purpose of this study is to evaluate the efficacy of two dose of CoronaVac® against RT-PCR confirmed symptomatic COVID-19 cases in participants aged 6 months to 17 years.

Detailed description: This study is a global multi-center , case-driven, randomized, double-blinded, and placebo-controlled phase Ⅲ clinical trial in participants aged 6 months to 17 years.The purpose of this study is to evaluate the efficacy of two dose of CoronaVac® against RT-PCR confirmed symptomatic COVID-19 cases in participants aged 6 months to 17 years.The experimental vaccine and placebo were both manufactured by Sinovac Research \& Development Co., Ltd. A total of 14,000 healthy participants aged 6 months to 17 years will be enrolled, and randomly assigned into 2 groups at a ratio of 1:1 to receive 2 doses of experimental vaccine (600SU) or placebo with an interval of 28 days.

Eligibility criteria: Inclusion Criteria:

* Healthy children and adolescents aged 6 months to 17 years;
* The participants and/or their guardians are able to understand and sign the informed consent voluntarily (in accordance with the local regulations);
* Able to comply with study procedures based on the assessment of the Investigator;
* Female participants of childbearing potential (post-menarche girls or in accordance with the local standard of care) may be enrolled in the study if the participant fulfills all the following criteria:

  * Has a negative pregnancy test on the day of the first dose (Day 0).
  * Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 0).
  * Has agreed to continue adequate contraception through 3 months following the second dose (Day 28).
  * Is not currently breastfeeding.
* Must be willing to provide verifiable identification (in accordance with the local regulations), has means to be contacted and to contact the investigator during the study.

Exclusion Criteria:

* History of confirmed infection of SARS CoV-2 prior to randomization;
* Close contact with a confirmed COVID-19 within 14 days prior to randomization;
* Prior administration of an investigational coronavirus vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID-19;
* Allergy to vaccines or vaccine/placebo ingredients, and serious adverse reactions to vaccines, such as urticaria, dyspnea, angioneuroedema;
* Personal or first-grade relative (siblings) history of multisystem inflammatory disease in children (MIS-C);
* Significant chronic illnesses that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion (may include, but are not limited to cardiovascular disease, liver or kidney disorders, respiratory illnesses)
* Significant chronic central nervous system diseases or neuromuscular disorders, psychosis or severe cognitive behavioral disorder, in the opinion of the investigator, including epilepsy, autism spectrum disorder, intellectual disabilities (excluding Down Syndrome);
* Acute central nervous system diseases such as encephalitis/myelitis, acute disseminating encephalomyelitis, and related disorders;
* History of autoimmune and/or haematological diseases (including but not limited to systemic lupus erythematosus, thyroidectomy, autoimmune thyroid disease, any form of malignant tumor, asplenia, functional asplenia, or splenectomy resulting from any condition); well controlled type I diabetes mellitus is allowed;
* History of bleeding disorders (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture;
* Immunosuppressive therapy (systemic corticoid therapy, e.g. prednisone ≥2 mg/Kg/d or ≥20 mg/day for \>14 days), cytotoxic therapy (antineoplastic chemotherapy, radiation therapy), (excluding topical or aerosol corticosteroid therapy) in the past 6 months;
* Receipt of blood products or immunoglobulins in the past 3 months;
* Receipt of other investigational drugs in the past 30 days;
* Receipt of attenuated live vaccines in the past 14 days;
* Receipt of inactivated or subunit vaccines in the past 7 days;
* Acute exacerbation or presentation of stable chronic diseases (including but not limited to asthma, migraine, gastrointestinal disorder, etc;
* Acute febrile illness with oral temperature \>37.7°C or axillary temperature \>37.5°C on the day of vaccination (refer to section 7.1 Delay/Discontinuation of Study Vaccination); enrollment could be considered if the fever is absent for 72 hours;
* Any confirmed or suspected human immunodeficiency virus (HIV) infection;
* Children in care or under a court order;
* According to the investigator's judgment, the subject has any other factors that might interfere with the results of the clinical trial or pose additional risk to the subject due to participation in the study.

Primary outcomes:
measure: Efficacy index-incidence of RT-PCR confirmed symptomatic COVID-19 cases with onset
timeFrame: 14 days after the second dose
Secondary outcomes:
measure: Efficacy index-incidence of RT-PCR confirmed symptomatic COVID-19 cases with onset
timeFrame: 14 days after the first dose
measure: Efficacy index-incidence of RT-PCR confirmed, symptomatic COVID-19 cases with onset in SARS-CoV-2 uninfected participants
timeFrame: 14 days after the second dose
measure: Efficacy index-incidence of hospitalization/severe/death caused by COVID-19 with onset
timeFrame: 14 days after the second dose
measure: Safety index-occurrence, intensity, duration, and relationship of solicited local and systemic AEs and of unsolicited AEs
timeFrame: During 7 days following each dose vaccination and during 28 days post-vaccination
measure: Safety index-occurrence and relationship of SAEs
timeFrame: From first dose to 12 months after the last dose
measure: Safety index-occurrence and relationship of AESI
timeFrame: From first dose to 12 months after the last dose
measure: Immunogenicity index(subgroup)-SARS-CoV-2 neutralizing antibody titers
timeFrame: From first dose to 12 months after the last dose
measure: Immunogenicity index(subgroup)-Anti-SARS-CoV-2 S
timeFrame: From first dose to 12 months after the last dose
Other outcomes:
Locations:
city: Puerto Montt
country: Chile
facility: Hospital de Puerto Montt
state: Los Lagos
city: Valdivia
country: Chile
facility: Clínica Alemana Valdivia
state: Los Ríos
city: Antofagasta
country: Chile
facility: Hospital Universidad Clinico de Antofagasta
state: Metropolitana
city: Independencia
country: Chile
facility: Hospital Roberto del Río
state: Metropolitana
city: Las Condes
country: Chile
facility: Clínica San Carlos de Apoquindo
state: Metropolitana
city: Las Condes
country: Chile
facility: Clínica Universidad de los Andes
state: Metropolitana
city: Macul
country: Chile
facility: San Joaquín
state: Metropolitana
city: Puente Alto
country: Chile
facility: Hospital Sótero del Río
state: Metropolitana
city: San Miguel
country: Chile
facility: Hospital Ezequial Gonzalez
state: Metropolitana
city: Santiago
country: Chile
facility: Marcoleta
state: Metropolitana
city: Vitacura
country: Chile
facility: Clínica Alemana
state: Metropolitana
city: Viña del Mar
country: Chile
facility: Hospital Gustavo Fricke
state: Valparaíso
city: Kota
country: Malaysia
facility: Hospital Wanita dan Kanak-Kanak Sabah
state: Kinabalu Sabah
city: Cheras
country: Malaysia
facility: Klinik Kesihatan Cheras Baru
state: Kuala Lumpur
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
state: Perak
city: Seberang Jaya
country: Malaysia
facility: Hospital Seberang Jaya
state: Pulau Pinang
city: Miri
country: Malaysia
facility: Hospital Miri
state: Sarawak
city: Sibu
country: Malaysia
facility: Hospital Sibu
state: Sarawak
city: Bandar
country: Malaysia
facility: Hospital Pengajar UiTM Puncak Alam
state: Selangor
city: Pelabuhan Klang
country: Malaysia
facility: Klinik Kesihatan Pandamaran
state: Selangor
city: Sungai Buloh
country: Malaysia
facility: Hospital Sungai Buloh
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Manila
country: Philippines
facility: National Children's Hospital
city: Manila
country: Philippines
facility: Philippine Children's Medical Center
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Manila
country: Philippines
facility: University of Philippines, National Institute of Health
city: Muntinlupa
country: Philippines
facility: Asian Hospital and Medical Center
city: Ga-Rankuwa
country: South Africa
facility: Mecru Clinical Research Unit
state: Gauteng
city: Bellville
country: South Africa
facility: Mecru Clinical Research Unit
city: Bellville
country: South Africa
facility: Tiervlei Trial Centre
city: Benoni,
country: South Africa
facility: Worthwhile Clinical Trials
city: Boksburg
country: South Africa
facility: Reimed Reicherpark
city: Johannesburg
country: South Africa
facility: Newtown Clinical Research Centre
city: Madibeng
country: South Africa
facility: Madibeng Centre for Research
city: Paarl
country: South Africa
facility: Be Part Research
city: Pretoria
country: South Africa
facility: Global Clinical Trials
city: Sandton
country: South Africa
facility: Sandton Medical Research Centre
city: Soweto
country: South Africa
facility: Soweto Clinical Trials Center
Study officials:
affiliation: Facultad de Medicina, Pontlficla Universidad Católica de Chile
name: Zeng Gang, Doctor
role: STUDY_DIRECTOR
References:
citation: Soto JA, Melo-Gonzalez F, Gutierrez-Vera C, Schultz BM, Berrios-Rojas RV, Rivera-Perez D, Pina-Iturbe A, Hoppe-Elsholz G, Duarte LF, Vazquez Y, Moreno-Tapia D, Rios M, Palacios PA, Garcia-Betancourt R, Santibanez A, Pacheco GA, Mendez C, Andrade CA, Silva PH, Diethelm-Varela B, Astudillo P, Calvo M, Cardenas A, Gonzalez M, Goldsack M, Gutierrez V, Potin M, Schilling A, Tapia LI, Twele L, Villena R, Grifoni A, Sette A, Weiskopf D, Fasce RA, Fernandez J, Mora J, Ramirez E, Gaete-Argel A, Acevedo ML, Valiente-Echeverria F, Soto-Rifo R, Retamal-Diaz A, Munoz-Jofre N; PedCoronaVac03CL Study Group,; Meng X, Xin Q, Alarcon-Bustamante E, Gonzalez-Aramundiz JV, Le Corre N, Alvarez-Figueroa MJ, Gonzalez PA, Abarca K, Perret C, Carreno LJ, Bueno SM, Kalergis AM. Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children. mBio. 2022 Dec 20;13(6):e0131122. doi: 10.1128/mbio.01311-22. Epub 2022 Nov 16.