A Single-blind Phase 1 Study Assessing the Safety, Immunogenicity and Low Density Lipoprotein Cholesterol (LDLc)-Lowering Activity of 2 Different Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Targeting AFFITOPE® Vaccines in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Affiris AG
- 入组人数
- 72
- 试验地点
- 2
- 主要终点
- Occurence of any Serious Adverse Event (SAE)
研究概览
简要总结
Study AFF012 is a single blind, single-center, randomized, placebo-controlled, parallel group, phase I clinical trial of repeated administration by subcutaneous injection of a single dose of one of two different proprotein convertase subtilisin/kexin type 9 targeting AFFITOPE® vaccines or Placebo. This study will assess Safety, Immunogenicity and low density lipoprotein cholesterol-lowering activity of the two vaccines.
72 healthy subjects are divided into three test groups (2 treatment groups, 1 placebo group), each consisting of 24 subjects. The subjects are randomized to receive either of two AFFITOPEs® (AT04A or AT06A, adsorbed to 1 mg aluminium oxyhydroxide) or placebo (1 mg aluminium oxyhydroxide).
The study consists of 3 parts, part A, encompassing Visit 1 to Visit 8, covering 3 priming immunizations at a dose of 15μg at days 0, 28 and 56 and the immediate observation period extending to day 140; the prolonged observation period: part B, encompassing Visit 9 and Visit 10 at days 273 and 365; and part C consisting of 7 visits (V11 to V17). Study participants having received 3 priming vaccinations and having completed part B will receive in part C one boost immunization at a dose of 75μg, which will be applied one year after the 3rd immunization (day 420). Probands will proceed directly from part A to part B and to part C. Continuation of parts B and C will be considered based on the part A results, primarily the immunological results. The following scenarios apply (provided that there is no safety issue). None of the two treatment groups exhibits a vaccine-specific antibody response over the placebo group at Visit 8 - this will lead to termination of the trial. One of the two groups fails to exhibit a vaccine-specific antibody response over the placebo group at Visit 8 - this will lead to its discontinuation; the other treatment group and the placebo group will be continued.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects ≥ 18 years of age at time of study entry.
- •Fasting LDLc at screening.
- •Fasting triglycerides at screening.
- •Body weight > 50 kg and a body mass index (BMI) between 19 and 35.
排除标准
- •Treatment/change in treatment with medications known to influence HDLc, LDLc and total cholesterol concentrations
- •Planned life-style changes during the study period like increasing aerobic exercise activity, attempting to lose body weight or changing the smoking status.
- •History of autoimmune diseases.
- •History of malignancy
- •Active or passive vaccination
- •Blood donation
- •History of severe hypersensitivity reactions and anaphylaxis.
- •History of allergic bronchial asthma.
- •Acquired or hereditary immunodeficiency.
- •Prior and/or current treatment with immune modulating drugs:
- •Subject has taken prescription lipid-regulating drugs
- •Treatment prior to screening with the following drugs: vitamin A derivatives and retinol derivatives for dermatologic treatment or any other drug known to influence cholesterol Levels
- •Infection with the human immunodeficiency Virus,Hepatitis B (HBsAg) or Hepatitis C.
研究组 & 干预措施
AFFITOPE® AT04A+adjuvant
3 injections of 15µg AFFITOPE® AT04A+adjuvant once every 4 weeks and 1 boost immunization at a dose of 75μg, which will be applied one year after the 3rd immunization
干预措施: AFFITOPE® AT04A+adjuvant (Biological)
AFFITOPE® AT06A+adjuvant
3 injections of 15µg AFFITOPE® AT06A+adjuvant once every 4 weeks and 1 boost immunization at a dose of 75μg, which will be applied one year after the 3rd immunization
干预措施: AFFITOPE® AT06A+adjuvant (Biological)
Adjuvant without active component
3 injections of Placebo once every 4 weeks and 1 boost immunization which will be applied one year after the 3rd immunization
干预措施: Adjuvant without active component (Biological)
结局指标
主要结局
Occurence of any Serious Adverse Event (SAE)
时间窗: 21 months
Evaluation of SAE being unlikely, possibly, probably or definitely related to the study vaccines Occurence of any Grade 3 or higher adverse Event (AE) Occurence of solicited local AEs Occurence of solicited systemic AEs Occurence of unsolicited non-serious AEs
次要结局
- Mean Levels of High Density Lipoprotein Cholesterol (HDLc)(21 months)
- Immunological activity of AFFITOPE® AT06A: Titer of vaccination-induced antibodies(21 months)
- Mean Levels of Total Cholesterol (TC)(21 months)
- Mean Levels of Triglycerides (TG)(21 months)
- Immunological activity of AFFITOPE® AT04A: Titer of vaccination-induced antibodies(21 months)
- Mean Levels of Very Low Density Lipoprotein (VLDL)(21 months)
- Mean Levels of PCSK9(21 months)
- Mean Levels of Low Density Lipoprotein Cholesterol (LDLc)(21 months)
- Correlation analysis: Relating the strength of antibody responses to Lipid lowering effects(21 months)