A Phase IV Double Blind Randomised Controlled Trial (DBRCT) to Investigate the Effect of PCV-13 and PPV-23 on Pneumococcal Colonisation Using the Experimental Human Pneumococcal Challenge (EHPC) Model in Healthy Adults
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 516
- 试验地点
- 1
- 主要终点
- The rate of experimental pneumococcal colonisation with SPN3 determined by the presence of pneumococcus in nasal wash (NW) by classical culture or molecular methods
研究概览
简要总结
To determine the effect of PCV-13 and PPV-23 vaccination versus control on experimental pneumococcal colonisation of 2 clades of serotypes 3 and 6B at 1 month and 6 months post vaccination respectively, using the EHPC model.
详细描述
Streptococcus pneumoniae (SPN) is the leading cause of morbidity and mortality worldwide, causing community acquired pneumonia (CAP), bacterial meningitis and bacteremia. Pneumococcal infections cause over 1 million pneumonia deaths per year in children in the developing world and is a major burden of otitis media globally.
The LSTM Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of measuring pneumococcal colonization of bacteria, understanding the effect of pneumococcal colonization on acquired immunity, and allows vaccines to be tested in adults to understand their effect on colonization in a manner which is cost-effective and uses much smaller numbers of participants compared to large phase III clinical trials.
Participants: Healthy adults aged 18-50 years of age (inclusive) will be recruited. A recruitment target of up to 516 participants with an approximate screen failure/dropout rate of 20% will ensure 410 participants complete Part A and 246 complete Part A & B of the trial.
Methods: Double blind randomized controlled trial (DBRCT) to investigate the effect of PCV-13 and PPV-23 vaccination on pneumococcal colonisation using the EHPC model in healthy adults. Participants will be randomised to 5 arms for Part A of the study that:
- to receive PCV-13 vaccine IM and inoculation a month later with SPN3 clade 1a;
- to receive PCV-13 vaccine IM and inoculation a month later with SPN3 clade 2;
- to receive PPV-23 vaccine IM and inoculation a month later with SPN3 clade 1a;
- to receive 0.9% saline for injection IM and inoculation a month later with SPN3 clade 1a or
- to receive 0.9% saline for injection IM and inoculation a month later with SPN3 clade 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants will remain blinded until the completion of the last participant, last study visit (Day 23: 7-month challenge). As the appearance of the vaccines are different, physical blindfolds may be worn by the participant to maintain blinding. This method of blinding has been used by our team previously and the time wearing the blindfold is kept to an absolute minimum for participant comfort. Un-blinded clinical team members will prepare and administer the vaccines/placebo to the participants in a blinded manner, shielding the vaccine formula, syringe and box from the participant when it is administered. The vaccine will be checked and prepared in a separate room to the participant and in a separate location to the blinded team. The participant will be seated in the vaccination room, the un-blinded clinical members will enter the vaccination room immediately prior to administration. Local SOPs will be followed to ensure appropriate participant team blinding.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults aged 18-50 years (inclusive)
- •Fluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement
- •Capacity to provide written informed consent
- •Females of childbearing potential with a negative urine pregnancy test at screening and willing to practice adequate birth control measures during the study.
排除标准
- •Be currently involved in another study unless observational or non-interventional. Exceptions are the EHPC bronchoscopy study and COVID-19 observational and interventional trials. The exceptions will be applied at the discretion of the Chief Investigator to ensure no harm comes to the participants (e.g. excessive blood sampling)
- •Be a participant in a previous EHPC trial within the last 3 years (at the discretion of the study team).
- •Vaccination (self-reported or confirmed from GP questionnaire [GPQ] or medical summary if deemed necessary at clinician discretion): Have had any previous pneumococcal vaccination (including in a research study).
- •Have allergy to penicillin or amoxicillin.
- •Have previous anaphylaxis or severe adverse reaction to any component/excipient of the vaccines or to any vaccine.
- •Health history (self-reported by the participant or confirmed in GPQ or medical summary if deemed necessary at clinician discretion): Ill health including but not limited to:
- •Asplenia or dysfunction of the spleen.
- •Chronic respiratory disease (e.g. asthma [on medication], COPD, emphysema, bronchiectasis).
- •Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) [controlled stable hypertension may be included].
- •Chronic kidney disease (e.g. nephrotic syndrome, kidney transplant, on dialysis).
- •Chronic liver disease (e.g. cirrhosis, biliary atresia, hepatitis).
- •Chronic neurological conditions
- •Connective tissue disease
- •Diabetes mellitus (including diet controlled).
- •Immunosuppression or history of receiving immunosuppressive therapy.
- •Individuals with cochlear implants.
- •Individuals with major cerebrospinal fluid leaks (e.g. following trauma, major skull surgery, or requiring CSF shunt).
- •Recurrent otitis media.
- •Have any uncontrolled medical/surgical conditions (such as but not restricted to mental health conditions, epilepsy, narcolepsy or chronic pain) at the discretion of the study doctor.
- •Major pneumococcal illness requiring hospitalisation within the last 10 years
- •Other conditions considered by the clinical team as a concern for participant safety or integrity of the study.
- •Taking medication:
- •That may affect the immune system e.g. steroids, inflammation altering (e.g. nasal steroids, Roaccutane) or disease-modifying anti-rheumatoid drugs.
- •Long-term use of antibiotics (see also section 6.3 Temporary exclusion criteria).
- •Nitroglycerin
- •That affects blood clotting (any oral/injectable anticoagulants [except aspirin]).
- •Female participants who are pregnant, lactating or intending on becoming pregnant during the study.
- •Direct caring role or close contact with individuals at higher risk of infection (during the challenge period)
- •Children under 5 years age.
- •Chronic ill health or immunosuppressed adults.
- •People that are part of the extremely vulnerable group as defined by Public Health England (PHE)
- •Current or ex-smoker (regular cigarettes/cigars/e-cigarette/vaping/smoking of recreational drugs) in the last 6 months.
- •Previous significant smoking history (more than 20 cigarettes per day for 20 years or the equivalent [>20 pack years]).
- •History or current drug or alcohol abuse (frequently drinking alcohol): men and women should not regularly drink >3 units/day and >2 units/day respectively) at discretion of the clinician.
- •Significant mental health problems (uncontrolled condition or previous admission in a psychiatric unit, at the discretion of the clinician) that would impair the participant's ability to participate in the study
- •Overseas travel planned: Overseas travel during the follow-up period Part A or Part B.
- •Participants who meet STOP criteria at the time of screening, as detailed in Table
- •Any other issue which, in the opinion of the study staff, may
- •Put the participant or their contacts at risk because of participation in the study,
- •Adversely affect the interpretation of the study results, or
- •Impair the participant's ability to participate in the study.
结局指标
主要结局
The rate of experimental pneumococcal colonisation with SPN3 determined by the presence of pneumococcus in nasal wash (NW) by classical culture or molecular methods
时间窗: any time point during 23 days following experimental human pneumococcal challenge (EHPC) 1 month after vaccination in the PCV-13, PPV-23 and control groups.
The rate of experimental pneumococcal colonisation with SPN3 determined by the presence of pneumococcus in nasal wash (NW) by classical culture or molecular methods at any time point during 23 days following experimental human pneumococcal challenge (EHPC) 1 month after vaccination in the PCV-13, PPV-23 and control groups.
次要结局
未报告次要终点