Hypercholesterolemia
Conditions
Brief summary
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.
Interventions
BIOLOGICALAFFITOPE® AT04A+adjuvant
subcutaneous injection
BIOLOGICALAFFITOPE® AT06A+adjuvant
subcutaneous injection
BIOLOGICALAdjuvant without active component
subcutaneous injection
Sponsors
Medical University of Vienna
Affiris AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subjects ≥ 18 years of age at time of study entry. 2. Fasting LDLc at screening. 3. Fasting triglycerides at screening. 4. Body weight \> 50 kg and a body mass index (BMI) between 19 and 35.
Exclusion criteria
1. Treatment/change in treatment with medications known to influence HDLc, LDLc and total cholesterol concentrations 2. Planned life-style changes during the study period like increasing aerobic exercise activity, attempting to lose body weight or changing the smoking status. 3. History of autoimmune diseases. 4. History of malignancy 5. Active or passive vaccination 6. Blood donation 7. History of severe hypersensitivity reactions and anaphylaxis. 8. History of allergic bronchial asthma. 9. Acquired or hereditary immunodeficiency. 10. Prior and/or current treatment with immune modulating drugs: 11. Subject has taken prescription lipid-regulating drugs 12. 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 13. Infection with the human immunodeficiency Virus,Hepatitis B (HBsAg) or Hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurence of any Serious Adverse Event (SAE) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunological activity of AFFITOPE® AT06A: Titer of vaccination-induced antibodies | 21 months | Titer of vaccination-induced antibodies directed towards peptide components of the vaccine, the carrier, and the target proprotein convertase subtilisin/kexin type 9 |
| Mean Levels of Low Density Lipoprotein Cholesterol (LDLc) | 21 months | Change from baseline |
| Mean Levels of High Density Lipoprotein Cholesterol (HDLc) | 21 months | Change from baseline |
| Mean Levels of Very Low Density Lipoprotein (VLDL) | 21 months | Change from baseline |
| Immunological activity of AFFITOPE® AT04A: Titer of vaccination-induced antibodies | 21 months | Titer of vaccination-induced antibodies directed towards peptide components of the vaccine, the carrier, and the target proprotein convertase subtilisin/kexin type 9 |
| Mean Levels of Triglycerides (TG) | 21 months | Change from baseline |
| Mean Levels of PCSK9 | 21 months | Change from baseline |
| Correlation analysis: Relating the strength of antibody responses to Lipid lowering effects | 21 months | Relating the strength of antibody responses to Lipid lowering effects |
| Mean Levels of Total Cholesterol (TC) | 21 months | Change from baseline |
Countries
Austria
Outcome results
None listed