An Open-label Phase 1 Study Assessing the Safety, Immunogenicity and Dose Response of IC84, a New Vaccine Against Clostridium Difficile, in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 3
- 主要终点
- Rate of subjects with solicited systemic AEs (headache, muscle pain, fever, flu-like symptoms, nausea, vomiting, rash, excessive fatigue) within 1 week (Day 0 6) after each vaccination: Severity and duration.
研究概览
简要总结
An open-label Phase 1 Study Assessing the Safety, Immunogenicity and Dose Response of IC84, A new vaccine against Clostridium Difficile (C. difficile), In healthy subjects
详细描述
This is an open-label, partially randomized, dose escalation Phase 1 study which will consist of a part A in healthy adults aged between ≥18 and <65 years and a part B in healthy elderly ≥65 years, the latter age group being the most vulnerable population to suffer from C. difficile infections.
Part A consists of 3 vaccinations on Day0, Day7 and Day21 with the following groups:
Group A: IC84 20 mcg (microgram)with Alum Group B: IC84 75 mcg (microgram)with Alum Group C: IC84 75 mcg (microgram)without Alum Group D: IC84 200 mcg(microgram)with Alum Group E: IC84 200 mcg(microgram)without Alum
Part A was already finished and part B is now ongoing. All information which could be find under the other sections are referring to the information on Part B.
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
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults ≥18 years of age.
- •No clinically relevant pathological findings in any of the investigations at the Screening Visit including subjects with pharmacologically controlled conditions like hypercholesterolemia, hypertension, cardiovascular disease or non insulin-dependent diabetes mellitus. Minor deviations of laboratory values from the normal range may be accepted, if judged by the investigator to have no clinical relevance.
- •In female subjects, either childbearing potential terminated by surgery or 1 year post menopausal, or a negative serum pregnancy test during screening and the willingness not to become pregnant during the entire study period by practicing reliable methods of contraception.
- •Weight: ≥ 45.5 kg and <= 150 kg at Visit 0 (Screening Visit).
- •White blood cells ≥2,500/mm3 and <11,000/mm3 at Visit
- •Platelets within normal limits at Visit
- •Written informed consent obtained from the subject prior to any study related procedures.
排除标准
- •Use of any other investigational or non-registered medicinal product within 30 days prior to IC84 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.
- •Immunodeficiency including status post-organ-transplantation or immuno-suppressive therapy, and a family history of congenital or hereditary immunodeficiency.
- •Infection with the human immunodeficiency virus (HIV, a negative test result within 30 days before screening is acceptable), Hepatitis B virus (HBV, Hepatitis B surface antigen [HBsAg]) or Hepatitis C virus (HCV).
- •History of severe hypersensitivity reactions and anaphylaxis.
- •History of allergic bronchial asthma and severe allergic rhinoconjunctivitis.
- •Known hypersensitivity or allergic reactions to one of the components of the vaccine.
- •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.
- •Clinically significant hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders, which are not adequately controlled by medical treatment within the last 12 weeks before IC84 vaccination at Visit 1 (Day 0) as judged by the site's Principal Investigator.
- •Systemic antibiotic use within four weeks prior to first vaccination and during treatment period (until Day 28).
- •Clinically significant diseases as judged by the investigator.
- •Administration of chronic (defined as longer than 14 days) immunosuppressants or other immune-modifying drugs within 30 days prior to IC84 vaccination at Visit 1 (Day 0) and during the study until Visit 5 (Day 28). (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 IC84 vaccination at Visit 1 (Day 0) and until Visit 5 (Day 28).
- •Intake of NSAID within three days prior to and within three days after all three vaccinations (Day 0, 7 and 21).
- •Acute febrile infections or exacerbation of chronic infection within four weeks prior to first vaccination at Visit 1 and during treatment period (until Day 21).
- •Body temperature > 37°C (oral) immediately prior to each vaccination.
- •Drug addiction within 6 months prior to Visit 0 [including alcohol dependence, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day] indicated by an elevated MCV above normal value at the Screening Visit.
- •Inability or unwillingness to avoid more than the usual intake of alcohol [i.e., not more then 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day] during the 48 hours after vaccination.
- •Pregnancy (positive pregnancy test during screening), lactation or unreliable contraception in female subjects with child-bearing potential ( and unreliable contraception in male subjects.
- •Not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
- •Blood donation within 4 weeks prior to first vaccination.
- •Clinically significant mental disorder not adequately controlled by medical treatment.
- •History of Guillain-Barré-Syndrome (GBS).
- •Any condition which might interfere with study objectives or would limit the subject's ability to complete the study in the opinion of the investigator.
- •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).
研究组 & 干预措施
IC84, 200 µg w/o Alum
200 µg w/o Alum (microgram without Alum)
干预措施: IC84 (Biological)
IC84, 200 µg w/ Alum
200 µg w/ Alum (microgram with Alum)
干预措施: IC84 (Biological)
IC84, 75 µg w/o Alum
75 µg w/o Alum (microgram without Alum)
干预措施: IC84 (Biological)
IC84, 75 µg w/ Alum
75 µg w/ Alum (microgram with Alum)
干预措施: IC84 (Biological)
结局指标
主要结局
Rate of subjects with solicited systemic AEs (headache, muscle pain, fever, flu-like symptoms, nausea, vomiting, rash, excessive fatigue) within 1 week (Day 0 6) after each vaccination: Severity and duration.
时间窗: 6 days after vaccination
Rate of subjects with unsolicited non-serious AEs (including safety laboratory parameters (hematology, serum chemistry, urinalysis) during treatment phase (i.e., until Day 28): Severity and causality.
时间窗: day 28
Rate of subjects with solicited local AEs (Adverse Events) (injection site pain, tenderness, redness, swelling, induration, itching) within 1 week (Day 0-6) after each vaccination: Severity and duration.
时间窗: 6 days after vaccination
Rate of subjects with unsolicited non-serious AEs (including safety laboratory parameters (hematology, serum chemistry, urinalysis)) within 6 months after last vaccination: Severity and causality.
时间窗: day 201
Rate of subjects with any SAE (Serious Adverse Event) possibly, probably or certainly related to the study vaccine at any time during the study
时间窗: day 201
Rate of subjects with any unsolicited or solicited Grade 3 or higher adverse event possibly, probably or certainly related to the study vaccine during treatment phase (i.e. until Day 28)
时间窗: day 201
Rate of subjects with any unsolicited or solicited Grade 3 or higher adverse event possibly, probably or certainly related to the study vaccine at any time during the study
时间窗: day 201
次要结局
- Determination of vaccine-induced C. difficile Toxin A- and Toxin B-neutralizing antibody levels on Day 0, 7, 14, 21, 28, 113 and 201 after the first vaccination using a Toxin Neutralization Assay (TNA)(day 201)
- Determination of vaccine (IC84) specific IgG levels on Day 0, 7, 14, 21, 28, 113 and 201 after the first vaccination using an Enzyme-Linked Immunosorbent Assay (ELISA)(day 201)
- Determination of C. difficile Toxin A- and Toxin B-specific IgG levels on Day 0, 7, 14, 21, 28, 113 and 201 after the first vaccination using an Enzyme-Linked Immunosorbent Assay (ELISA)(day 201)