Dose Confirmation, Immunogenicity and Safety Study of the Clostridium Difficile Vaccine Candidate VLA84 in Healthy Adults Aged 50 Years and Older. Randomized, Controlled, Observer Blind Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 500
- 试验地点
- 17
- 主要终点
- Seroconversion Rate (SCR) on Day 56
研究概览
简要总结
Phase 2, randomized, observer-blind, placebo-controlled, multi-centric study including 4 parallel study groups.
500 Subjects (thereof, 250 aged 50 - 64 years and 250 aged 65 years and older) will be randomized in a (3:3:3:1) ratio to receive either VLA84 75 µg w/o (without) Alum, VLA84 200 µg w/o Alum, VLA84 200 µg w/ (with) Alum (150 subjects each), or placebo (50 subjects), as i.m. (intramuscular) vaccinations into alternating arms, on Days 0, 7 and 28
详细描述
This is a randomized, controlled, observer-blind Phase 2 study which aims to confirm the optimal dose and formulation of VLA84 in healthy adults aged ≥ 50 years of age. The study will be enrolled in two age strata, subjects aged 50 - 64 years and subjects aged 65 years and older, in a 1:1 ratio.
500 subjects (thereof, 250 aged 50 - 64 years and 250 aged 65 years and older) will be randomized in a 3:3:3:1 ratio to receive either VLA84 75 µg w/o Alum, VLA84 200 µg w/o Alum, VLA84 200 µg w/ Alum (150 subjects each), or placebo (50 subjects). Vaccinations consist of two i.m. injections administered in close proximity to each other in the deltoid region at Day 0, 7 and 28, starting with the non-dominant arm and alternating arms between the vaccination days.
The study will investigate the immunogenicity and safety of VLA84 up to six months after the last vaccination, i.e. 210 days per subject. The study includes eight outpatient visits on days 0, 7, 14, 28, 35, 56, 120 and 210. Serum will be collected to assess humoral immunity at days 0, 7, 14, 28, 35, 56, 120 and 210.
The study is OBSERVER blind. This means only pre-defined study staff will be unblinded, e.g., staff responsible for IMP accountability, preparation and administration, monitor responsible IMP accountability, or safety staff in case of safety reasons. All other persons involved in study conduct will remain blinded.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects aged ≥50 years of good general health, including subjects with pharmacologically controlled conditions like hypercholesterolemia, hypertension, or type 2 diabetes mellitus.
- •Informed consent form has been signed and dated
排除标准
- •Subjects with any confirmed or suspected prior Clostridium difficile infection episode
- •Previous vaccination against Clostridium difficile with any (investigational) vaccine or receipt of (investigational) monoclonal antibodies against Clostridium difficile toxins
- •Use of any other investigational or non-registered medicinal product within 30 days prior to VLA84 vaccination at Visit 1 (Day 0) and throughout the entire study period.
- •Active or passive vaccination four weeks before first vaccination at Visit 1 and during the entire study period, except for influenza (seasonal or pandemic) and pneumococcal vaccines which may be administered outside a 7-days interval before and after any trial vaccination
- •Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile)
- •Known thrombocytopenia, bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion or until Visit 4 (Day28), contraindicating i.m. vaccination as judged by the investigator
- •Clinically relevant renal, hepatic, cardiac, pulmonary or central nervous disorders, as judged by the investigator. Subjects with hypercholesterolemia, hypertension, or type 2 diabetes mellitus requiring medication are allowed if disease is adequately controlled
- •Receipt of blood or blood-derived products in the past 3 months or anticipation of such products during the study period
- •Known congenital, hereditary or acquired immunodeficiency, including known infection with human immunodeficiency virus (HIV), administration of chronic (defined as longer than 14 days) immunosuppressants or other immune-modifying drugs within 30 days prior to VLA84 vaccination at Visit 1 (Day 0) and during the study until Visit 5 (Day 35). For corticosteroids this means prednisone or equivalent ≥ 0.05 mg/kg/day; topical and inhaled steroids are allowed. Periodic steroid injections, e.g., intra-articular, are not allowed within 30 days prior to first VLA84 vaccination at Visit 1 (Day 0) and until Visit 5 (Day 35)
- •History of autoimmune disease, including Type I Diabetes mellitus. Subjects with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded
- •Any malignancy in the past 5 years. If treatment for cancer was successfully completed more than 5 years ago and the malignancy is considered to be cured, the subject may be enrolled
- •Known hypersensitivity or allergic reactions to one of the components of the vaccine
- •Inability or unwillingness to provide informed consent
- •Persons who are committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities)
- •Persons who are in a dependent relationship with the sponsor, an investigator or other study team members, or the study center. Dependent relationships include close relatives and household members (i.e., children, partner/spouse, siblings, parents) as well as employees of the investigator or study center personnel
结局指标
主要结局
Seroconversion Rate (SCR) on Day 56
时间窗: Day 56
Seroconversion Rate (SCR), defined as percentage of subjects achieving a ≥4-fold increase in antibody titer from Day 0, for IgG against both Toxin A and Toxin B on Day 56;
次要结局
- GMT for Toxin A Neutralizing Antibodies(Days 0, 35, 56, 120 and 210)
- SCR for IgG Against Toxin A, Against Toxin B and Against Both Toxin A and Toxin B Stratified by Age Group(Days 14, 28, 35, 56, 120 and 210)
- GMT for IgG Against Toxin A and Against Toxin B Stratified by Age Group(Days 0, 14, 28, 35, 56, 120, 210)
- Responder Rate (RR) for Toxin B Neutralizing Antibodies(Days 35, 56, 120 and 210)
- Rates of Study Participants With at Least One Solicited Local and Systemic AE(within 7 Days after each vaccination)
- Geometric Mean Titer (GMT) for IgG Against Toxin B(Days 0, 14, 28, 35, 56, 120 and 210)
- GMT for Toxin B Neutralizing Antibodies(Days 0, 35, 56, 120 and 210)
- Rate of Study Participants With at Least One Unsolicited AEs (Adverse Event)(Day 56 and Day 210)
- SCR for IgG (Immunoglobulin G) Against Both Toxin A and Toxin B(Days 14, 28, 35, 120 and 210)
- Seroconversion Rate (SCR) for IgG Against Toxin A(14, 28, 35, 56, 120 and 210)
- Seroconversion Rate (SCR) for IgG Against Toxin B(Days 14, 28, 35, 56, 120 and 210)
- Geometric Mean Titer (GMT) for IgG Against Toxin A(Days 0, 14, 28, 35, 56, 120 and 210)
- Responder Rate (RR) for Neutralizing Antibodies Against Toxin A, Against Toxin B and Against Both Toxin A and Toxin B Stratified by Age Group(Days 35, 56, 120 and 210)
- Rate of Study Participants With at Least One SAE (Serious Adverse Event)(Day 56 and Day 210)
- Rates of Study Participants With at Least One SAE, Related SAE, Unsolicited AE and Related Unsolicited AE Stratified by Age Group(Day 56 and Day 210)
- Rates of Study Participants With at Least One Solicited Local and Systemic AE Within 7 Days After Each and Any Vaccination Stratified by Age Group(within 7 Days after each vaccination)
- GMTs for Toxin A Neutralizing Antibodies and for Toxin B Neutralizing Antibodies Stratified by Age Group(Days 0, 35, 56, 120 and 210)
- Responder Rate (RR) for Neutralizing Antibodies Against Both Toxin A and Toxin B(Days 35, 56, 120, 210)
- Rate of Study Participants With at Least One Related SAE(Day 56 and Day 210)
- Rate of Study Participants With at Least One Related Unsolicited AE(Day 56 and Day 210)
- Responder Rate (RR) for Toxin A Neutralizing Antibodies(Days 35, 56, 120 and 210)