A randomized, phase 1, single-centre, observer-blind, active-controlled, 3-arm study to evaluate the safety, tolerability, and immunogenicity of a single administration of TETRALITE, a novel adjuvanted influenza vaccine, in healthy participants aged 18 to 50 years.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of a single administration of TETRALITE(3 microgram VaxiFlu-4™+0.5mg or 1mg adjuvant)versus15 microgram VaxiFlu 4™ without adjuvant in healthy participants(18-50years).
研究概览
简要总结
This is a Phase 1, randomized, controlled, observer-blinded clinical trial designed to evaluate the safety, tolerability, and immunogenicity of an investigational adjuvanted influenza vaccine, TETRALITE, in healthy adult volunteers in India.
The study will be conducted in healthy male and female adults aged 18 to 50 years who meet all eligibility criteria and provide written informed consent. Individuals with significant acute or chronic medical conditions, immunosuppressive disorders, or recent receipt of influenza vaccination within the protocol-defined exclusion period will be excluded.
Eligible participants will be randomized to one of three study arms:
• Intervention Arm 1: A single intramuscular injection of TETRALITE consisting of one-fifth dose of a licensed tetravalent inactivated split virion influenza vaccine (VaxiFlu-4™) combined with 0.5 mg of the novel adjuvant LVA.
• Intervention Arm 2: A single intramuscular injection of TETRALITE consisting of one-fifth dose of VaxiFlu-4™ combined with 1 mg of the novel adjuvant LVA.
• Comparator Arm: A single intramuscular injection of the full licensed dose of VaxiFlu-4™ (15 micrograms of hemagglutinin per strain) without adjuvant.
Randomization will be performed by an independent statistician using a computer-generated randomization sequence. Allocation concealment will be ensured using Sequentially Numbered, Opaque, Sealed Envelopes (SNOSE). The study will be observer-blinded; participants and outcome assessors will remain blinded to treatment allocation, while designated unblinded personnel will be responsible for vaccine preparation and administration.
The primary objectives of the study are to evaluate the safety and tolerability of a single dose of TETRALITE compared with the licensed influenza vaccine. Safety assessments will include monitoring of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events.
Secondary objectives include assessment of immunogenicity. Immune responses will be evaluated by measuring hemagglutination inhibition (HI) and microneutralization (MN) antibody titres against vaccine strains.
Following vaccination, participants will be observed on-site for a minimum of 60 minutes for immediate adverse events. Scheduled follow-up visits will occur on Day 8, Day 29, and Day 181 post-vaccination for safety assessments and collection of blood samples for immunogenicity analysis, as specified in the study protocol.
The total duration of individual participation in the study will be approximately six months. This Phase 1 study is intended to generate preliminary safety, tolerability, and immunogenicity data to support further clinical development of LVA-adjuvanted influenza vaccines and to inform the design of subsequent studies, including evaluation in older adults who represent the primary target population for influenza vaccination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 50.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Written and signed informed consent obtained before any study-related activities.
- •2.Aged 18 to 50 years (inclusive), at the time of signing the Informed Consent Form (ICF) 3.Participants who are considered to be in good general health as determined by a medical evaluation including medical history, Physical Examination (PE), and laboratory tests within 21 days prior to enrolment.
- •4.Participants with a Body Mass Index (BMI) within the range of 18.5 to 35 kg/m2 inclusive at screening.
- •5.No serologic markers of past or ongoing Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Human Immunodeficiency Virus (HIV) infection.
- •6.Women who are not pregnant or breastfeeding, and one of the following conditions applies: • Women of non-childbearing potential (WONCBP): Non-childbearing potential is defined as surgically sterilized (e.g. hysterectomy, bilateral oophorectomy, or tubal ligation/salpingectomy) or postmenopausal (defined as having no menstrual bleeding for at least 12 months) without an alternative medical cause prior to study.
- •(OR) • Women of Childbearing Potential (WOCBP) and using a highly effective contraceptive method (with a failure rate of less than 1 % per year),from at least one month prior to study vaccination and for 3 months post vaccination.
- •The investigator should evaluate the potential for contraceptive method failure (e.g. noncompliance, recently initiated) in relation to study vaccination.
- •Highly effective contraception is defined as stabilized on oral birth control for at least one month before study participation, intrauterine device/system, implant, injection, transdermal patch, vasectomized partner, or sexual abstinence (excluding periodic abstinence).
- •The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
- •The participant should commit her abstinence for at least one month prior to study vaccination and for 3 months’ post vaccination.
- •If the participant will not maintain abstinence and changes her status, the participant must first commit to another highly effective method of contraception, which should be discussed with the investigator prior to terminating sexual abstinence as a contraceptive method.
- •7.WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test before vaccination on day of randomization (Day 1).
- •The investigator is responsible for reviewing medical history and menstrual history to decrease the risk of inclusion of a woman with early undetected pregnancy.
排除标准
- •1.History of lab-confirmed influenza infection, excluding COVID-19, 12 months prior to the day of study vaccination.
- •2.Past history or current immune-mediated and/or autoimmune diseases as indicated by the investigator.
- •3.History of serious reactions to vaccines as determined by the investigator.
- •4.Clinical conditions which are a contraindication for IM administration, as judged by the investigator.
- •5.History of confirmed hypersensitivity, allergy, and/or anaphylaxis to eggs, squalene-based adjuvants, or other components of the study vaccine (neomycin, formaldehyde or octoxinol-9).
- •6.Uncontrolled medical illness (unstable for the past 3 months) as indicated by the investigator.
- •7.Past or current history of any neurological disorder,e.g. Guillain-Barré syndrome and seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years.
- •8.History of asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen.
- •9.Malignancy that is active, or treated for which there is not reasonable assurance of sustained cure, or that is likely to recur during the period of the study.
- •10.Asthma that is unstable or requires emergent care,hospitalization or intubation during the past two years or that is expected to require the use of oral or intravenous corticosteroids.
- •11.History of hereditary angioedema, acquired angioedema and/or idiopathic forms of angioedema.
- •12.History of idiopathic urticaria within the past year.
- •13.History of heavy smoking, drug/alcohol abuse/addiction or psychiatric condition which in the investigator’s opinion.
- •14.A rash, dermatological condition, or tattoos that would, in the opinion of the investigator, interfere with injection local reaction rating.
- •15.Receipt of a seasonal or pandemic influenza vaccination 6 months before administration of the study vaccine or planning to receive the influenza vaccination during the study period.
- •16.Receipt of an investigational pandemic influenza vaccine 6 months before administration of study vaccine or planning to receive such a product during the study period.
- •17.Receipt of a live attenuated vaccine, or subunit or inactivated vaccines 28 days prior to administration of the study vaccine, other than seasonal or pandemic influenza vaccination, excluding COVID-19 vaccine.
- •18.Receipt of a COVID-19 vaccine 7 days before administration of study vaccine.
- •19.Planning to receive any vaccine (other than influenza) during the first 28 days following the administration of the study vaccine.
- •20.Currently participating in another clinical study, or planning to participate in another study during the study period, or administration of any investigational drug or medical device in the 4 weeks prior to study vaccination.
- •22.Use of drugs that can affect immune response such as systemic corticosteroids (excluding topical preparations and inhaled preparations) or immunosuppressive drugs in the 30 days before study vaccination and/or in the first 28 days following study vaccination, with the exception that a short course of corticosteroids less than or equal to 10 days duration or a single injection for a self-limited condition at least 2 weeks prior to enrolment will not exclude study participation.
- •23.Current intake of drugs that increase bleeding risk, e.g. anticoagulant medication.
- •24.Current anti-tuberculosis prophylaxis or therapy.
- •25.Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and/or planning a medical procedure under full anaesthesia on the day of study vaccination and/or in the first 14 days following study vaccination with the exception of a medical indication.
- •26.WOCBP who are pregnant, breastfeeding or planning to become pregnant during the study.
- •27.Participants with a history of any medical conditions that, in the opinion of the investigator, might interfere with the results of the study.
- •29.Intake of antipyretics and/or analgesic medications within 24 hours prior to study vaccination.
结局指标
主要结局
To evaluate the safety and tolerability of a single administration of TETRALITE(3 microgram VaxiFlu-4™+0.5mg or 1mg adjuvant)versus15 microgram VaxiFlu 4™ without adjuvant in healthy participants(18-50years).
时间窗: 1.Occurrence of solicited local and systemic adverse events (AEs) for 7 days after vaccination. | 2.Occurrence of unsolicited AEs for 28 days after vaccination. | 3.Occurrence of serious adverse events (SAEs), potential immune-mediated disorders (pIMDs), and adverse events of special interest (AESIs) for 180 days after vaccination. | 4.Occurrence of clinically abnormal haematology and serum biochemistry laboratory values at 7 days, 28 days, and 180 days after vaccination versus baseline (Day1, pre-vaccination).
次要结局
- To evaluate humoral immune responses from a single administration of TETRALITE (3 microgram VaxiFlu-4™ + 1mg adjuvant) versus VaxiFlu-4™ without adjuvant (3 microgram and 15 microgram) in healthy participants (18-50 years).(Immunogenicity of TETRALITE will be determined by:)
- To evaluate the T cell immune responses from a single administration of TETRALITE (3 microgram VaxiFlu-4™ + 0.5 mg or 1mg adjuvant) versus 15 microgram VaxiFlu-4™ without adjuvant in healthy participants (18-50 years).(1. T cell-mediated immune response in PBMCs at 7 days, 28 days, and 180 days after vaccination versus baseline (Day 1, pre-vaccination) confirmed by the presence of influenza-specific CD4 plus and CD8 plus T cells producing at least CD40L, IL-2, Interferon gamma and/or TNF alpha, measured by flow cytometry (intracellular cytokine staining).)
- To further evaluate the humoral response from a single administration of TETRALITE (3 microgram VaxiFlu-4™ + 0.5 mg or 1mg adjuvant) versus 15 microgram VaxiFlu-4™ without adjuvant in healthy participants (18-50 years).(Additional assays may include but are not limited to cross-reactive antibodies.)
- To identify participants who have been infected with influenza virus during the study.(The measurement of anti-nucleoprotein (NP) Immunoglobulin G (IgG) concentration in serum samples at baseline (Day 1, pre-vaccination), 28 days, and 180 days after vaccination.)
研究者
Dr Ganesan Karthikeyan
BRIC - Translational Health Science and Technology Institute (THSTI)