Immunogenicity and Safety of Rabies Vaccine (Serum-free Vero Cell) in a Simulated Post-exposure Prophylaxis Regimen

Официальное название

Immunogenicity and Safety of a Rabies Vaccine (Serum-free Vero Cell), Freeze-dried in Comparison With Verorab®, in a Simulated Post-exposure Prophylaxis Regimen in Healthy Populations Aged ≥1 Years: A Randomized, Double-Blind, Active-controlled Phase Ⅲ Clinical Trial

Обзор

To demonstrate the immunogenicity of Sinovac rabies vaccine is non-inferior to the active-controlled rabies vaccine (Verorab®) after post-exposure prophylaxis (PEP) vaccination, and to confirm its satisfying safety profile in the pediatric and adult population in a PEP schedule

Подробное описание

This is a Phase Ⅲ, randomized, double-blind, active-controlled study. A total of 390 healthy participants aged ≥1 years old will be enrolled. All participants will be randomized at a 2:1 ratio to receive Sinovac rabies vaccine (Trial group) or Sanofi Pasteur Verorab® (Control group), in an Essen schedule of 5 doses at Day 0, Day 3, Day 7, Day 14, Day 28 through intramuscular route (IM) as a simulated rabies PEP.

Blood samples for immunogenicity assessment will be collected at Day 0, Day 14, Day 28, and Day 42. For safety assessment, the solicited local and systemic adverse events (AEs) within 7 days after each-dose vaccination (If the vaccination interval is less than 7 days, the actual interval shall prevail), as well as unsolicited AEs from the first-dose vaccination until 28 days after the last-dose vaccination will be actively monitored. Serious adverse events (SAEs) will also be collected during the whole study period.

Вмешательства

• Биопрепарат Rabies vaccine
  Receiving five doses of rabies vaccine manufactured by Sinovac using the "Essen" PEP schedule
• Биопрепарат Verorab®
  Receiving five doses of marketed rabies vaccine manufactured by Sanofi using the "Essen" PEP schedule

Первичные конечные точки

• Proportion of participants achieving a rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/mL [Срок оценки: Day 14 and Day 28 after the first dose vaccination]

Вторичные конечные точки (3)

• Geometric mean concentrations (GMCs) of RVNA titers [Срок оценки: Day 14, Day 28 and Day 42 after the first dose vaccination]
• Proportion of participants achieving a RVNA titer ≥0.5 IU/mL [Срок оценки: Day 42 after the first dose vaccination]
• Incidence of adverse reactions [Срок оценки: Up to 28 days after the last-dose vaccination]

Критерии участия

Критерии включения

• Populations aged ≥1 years old;
• Participants and/or participants' parents/legal guardians are able to understand and sign the informed consent form (ICF) voluntarily;
• Participants are able to comply with the study procedures based on the investigator's assessment;
• In a stable health status (defined as a stable preexisting disease status during the past 3 months, i.e., no change in treatment or hospitalization due to exacerbation of preexisting diseases);
• Participants were tested negative for HIV, Syphilis, Hepatitis B, Hepatitis C infection at the screening of this study (the test result should be provided);
• Female participants aged ≥15 years old with childbearing potential were tested negative for urine pregnancy test pre-vaccination, and also need to have effective contraceptive measures in the previous 2 weeks pre-vaccination.
• Participants of childbearing potential and their partners are willing to take effective contraceptive measures and have no sperm or ovum donation plan from the time of signing ICF to 28 days after the last dose of vaccination;
• Participants should provide verifiable identifications, and contact or be contacted with the investigators during the study period

Критерии исключения

• Fever on vaccination day, with axillary temperature >37.0°C (aged ≥5 years old) or >37.3°C (aged 1\~4 years old) pre-vaccination;
• Previous vaccination against rabies (in pre- or post-exposure regimen) with either trial vaccines or licensed vaccines;
• Previous administration with rabies immunoglobulins or monoclonal antibodies;
• Bite by, or exposure to a potentially rabid animal in the previous 12 months with category Ⅱ or Ⅲ exposures;
• Female participants who are currently lactating or pregnant;
• Known serious allergy to vaccines or vaccine ingredients, such as severe urticaria, anaphylactic shock, allergic laryngeal edema, allergic purpura, or known other serious adverse reactions to vaccine;
• With severe congenital malformations or developmental disorders, genetic defects, severe malnutrition;
• With autoimmune diseases, immunodeficiency diseases (including but not limited to systemic lupus erythematosus, ankylosing spondylitis, autoimmune thyroid diseases, asplenia, functional asplenia, and HIV infection);
• With poor controlled chronic illnesses or history of severe diseases, including but not limited to cardiovascular diseases, hematological disorders, liver and kidney diseases, digestive system disorders, respiratory diseases, malignancies, a history of major organ transplantation, drug-uncontrolled hypertension (only for participants aged ≥18 years old: with systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg), or any other disease or medical condition that the investigator believes could interfere with the trial results;
• With current or past history of severe neurological diseases (epilepsy, convulsions or seizures \[excluding history of febrile seizures\]) or psychiatric disorders, or presence of a family history of psychiatric disorders;
• With coagulation disorders (eg. factor deficiency, platelet disorders), or history of bleeding, hematoma, or bruising following intramuscular injections or venipuncture;
• Receipt of ≥14 days of immunosuppressive or other immunomodulatory therapy (prednisone ≥2mg/kg/day, or its equivalent), cytotoxic therapy within 180 days prior to screening, or plans for such treatment in this study;
• With long-term alcohol abuse \[>14 drinks per week (1 drink =14 g 100% alcohol =360 mL beer, or 150 mL wine, or 45 mL distilled liquor/liquor)\] or substance abuse (repeated and heavy use of narcotic drugs, psychotropic drugs, volatile organic solvents, etc.)
• Receipt of blood products or immunoglobulins within 180 days prior to screening, or plans to receive these treatments in the study;
• Receipt of other investigational drugs/vaccines within 30 days prior to screening, or plans to receive such drugs or vaccines during the study period;
• Currently participating in other vaccine or drug clinical trials, or plan to participate in other clinical trials during the study;
• Receipt of live-attenuated vaccines within 14 days prior to screening, or subunit or inactivated vaccines within 7 days prior to screening;
• Presence of skin injuries, inflammation, ulcers, rashes, scars, or other conditions at the intended vaccination site that may interfere with drug administration or observation of local reactions;
• Acute onset of various acute diseases or chronic diseases within the past 7 days, or known or suspected active infections;
• Any other factors considered by the investigator to make the participant unsuitable for participation in the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Пакистан · 1 центр

• Al-Shifa Trust Eye Hospital — Rawalpindi

Идентификаторы

NCT: NCT07055893 · PRO-PVRV-sf-3002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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