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Study Assessing Safety, Immunogenicity and LDLc -Lowering Activity of 2 PCSK9 Targeting AFFITOPE Vaccines in Healthy Subjects (AFF012)

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ClinicalTrials.gov Identifier: NCT02508896
Recruitment Status : Completed
First Posted : July 27, 2015
Last Update Posted : October 20, 2017
Sponsor:
Collaborator:
Medical University of Vienna
Information provided by (Responsible Party):
Affiris AG

Study Description
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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.


Condition or disease Intervention/treatment Phase
Hypercholesterolemia Biological: AFFITOPE® AT04A+adjuvant Biological: AFFITOPE® AT06A+adjuvant Biological: Adjuvant without active component Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2015
Actual Primary Completion Date : May 2016
Actual Study Completion Date : August 31, 2017

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Arms and Interventions
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Arm Intervention/treatment
Experimental: 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
 Biological: AFFITOPE® AT04A+adjuvant
subcutaneous injection
Experimental: 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
 Biological: AFFITOPE® AT06A+adjuvant
subcutaneous injection
Placebo Comparator: 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
 Biological: Adjuvant without active component
subcutaneous injection


Outcome Measures
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Primary Outcome Measures :
  1. Occurence of any Serious Adverse Event (SAE) [ Time Frame: 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 Outcome Measures :
  1. Immunological activity of AFFITOPE® AT04A: Titer of vaccination-induced antibodies [ Time Frame: 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

  2. Immunological activity of AFFITOPE® AT06A: Titer of vaccination-induced antibodies [ Time Frame: 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

  3. Mean Levels of Low Density Lipoprotein Cholesterol (LDLc) [ Time Frame: 21 months ]
    Change from baseline

  4. Mean Levels of High Density Lipoprotein Cholesterol (HDLc) [ Time Frame: 21 months ]
    Change from baseline

  5. Mean Levels of Very Low Density Lipoprotein (VLDL) [ Time Frame: 21 months ]
    Change from baseline

  6. Mean Levels of Total Cholesterol (TC) [ Time Frame: 21 months ]
    Change from baseline

  7. Mean Levels of Triglycerides (TG) [ Time Frame: 21 months ]
    Change from baseline

  8. Mean Levels of PCSK9 [ Time Frame: 21 months ]
    Change from baseline

  9. Correlation analysis: Relating the strength of antibody responses to Lipid lowering effects [ Time Frame: 21 months ]
    Relating the strength of antibody responses to Lipid lowering effects


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02508896


Locations
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Austria
Medical University of Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Affiris AG
Medical University of Vienna
Investigators
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Principal Investigator: Markus Zeitlinger, MD Medical University of Vienna
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Affiris AG
ClinicalTrials.gov Identifier: NCT02508896    
Other Study ID Numbers: AFFiRiS 012
2015-001719-11 ( EudraCT Number )
First Posted: July 27, 2015    Key Record Dates
Last Update Posted: October 20, 2017
Last Verified: October 2017
Additional relevant MeSH terms:
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Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases