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Trial record 1 of 1 for:    nct02508896
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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

Tracking Information
First Submitted Date  ICMJE July 24, 2015
First Posted Date  ICMJE July 27, 2015
Last Update Posted Date October 20, 2017
Study Start Date  ICMJE July 2015
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2016)
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
Original Primary Outcome Measures  ICMJE
 (submitted: July 24, 2015)
Occurence of any Serious Adverse Event (SAE) [ Time Frame: 12 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2016)
  • 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
  • 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
  • Mean Levels of Low Density Lipoprotein Cholesterol (LDLc) [ Time Frame: 21 months ]
    Change from baseline
  • Mean Levels of High Density Lipoprotein Cholesterol (HDLc) [ Time Frame: 21 months ]
    Change from baseline
  • Mean Levels of Very Low Density Lipoprotein (VLDL) [ Time Frame: 21 months ]
    Change from baseline
  • Mean Levels of Total Cholesterol (TC) [ Time Frame: 21 months ]
    Change from baseline
  • Mean Levels of Triglycerides (TG) [ Time Frame: 21 months ]
    Change from baseline
  • Mean Levels of PCSK9 [ Time Frame: 21 months ]
    Change from baseline
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2015)
  • Immunological activity of AFFITOPE® AT04A: Titer of vaccination-induced antibodies [ Time Frame: 12 months ]
    Titer of vaccination-induced antibodies directed towards peptide components of the vaccine, the carrier, and the target proprotein convertase subtilisin/kexin type 9
  • Immunological activity of AFFITOPE® AT06A: Titer of vaccination-induced antibodies [ Time Frame: 12 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) [ Time Frame: 12 months ]
    Change from baseline
  • Mean Levels of High Density Lipoprotein Cholesterol (HDLc) [ Time Frame: 12 months ]
    Change from baseline
  • Mean Levels of Very Low Density Lipoprotein (VLDL) [ Time Frame: 12 months ]
    Change from baseline
  • Mean Levels of Total Cholesterol (TC) [ Time Frame: 12 months ]
    Change from baseline
  • Mean Levels of Triglycerides (TG) [ Time Frame: 12 months ]
    Change from baseline
  • Mean Levels of PCSK9 [ Time Frame: 12 months ]
    Change from baseline
  • Correlation analysis: Relating the strength of antibody responses to Lipid lowering effects [ Time Frame: 12 months ]
    Relating the strength of antibody responses to Lipid lowering effects
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Assessing Safety, Immunogenicity and LDLc -Lowering Activity of 2 PCSK9 Targeting AFFITOPE Vaccines in Healthy Subjects
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Hypercholesterolemia
Intervention  ICMJE
  • Biological: AFFITOPE® AT04A+adjuvant
    subcutaneous injection
  • Biological: AFFITOPE® AT06A+adjuvant
    subcutaneous injection
  • Biological: Adjuvant without active component
    subcutaneous injection
Study Arms  ICMJE
  • 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
    Intervention: Biological: AFFITOPE® AT04A+adjuvant
  • 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
    Intervention: Biological: AFFITOPE® AT06A+adjuvant
  • 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
    Intervention: Biological: Adjuvant without active component
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 24, 2015)
72
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 31, 2017
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02508896
Other Study ID Numbers  ICMJE AFFiRiS 012
2015-001719-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Affiris AG
Study Sponsor  ICMJE Affiris AG
Collaborators  ICMJE Medical University of Vienna
Investigators  ICMJE
Principal Investigator: Markus Zeitlinger, MD Medical University of Vienna
PRS Account Affiris AG
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP