Overview

This trial is active, not recruiting.

Condition hypercholesterolemia
Treatments affitope® at04a+adjuvant, affitope® at06a+adjuvant, adjuvant without active component
Phase phase 1
Sponsor Affiris AG
Collaborator Medical University of Vienna
Start date July 2015
End date May 2016
Trial size 72 participants
Trial identifier NCT02508896, 2015-001719-11, AFFiRiS 012

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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking single blind (subject)
Primary purpose treatment
Arm
(Experimental)
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
affitope® at04a+adjuvant
subcutaneous injection
(Experimental)
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
affitope® at06a+adjuvant
subcutaneous injection
(Placebo Comparator)
3 injections of Placebo once every 4 weeks and 1 boost immunization which will be applied one year after the 3rd immunization
adjuvant without active component
subcutaneous injection

Primary Outcomes

Measure
Occurence of any Serious Adverse Event (SAE)
time frame: 21 months

Secondary Outcomes

Measure
Immunological activity of AFFITOPE® AT04A: Titer of vaccination-induced antibodies
time frame: 21 months
Immunological activity of AFFITOPE® AT06A: Titer of vaccination-induced antibodies
time frame: 21 months
Mean Levels of Low Density Lipoprotein Cholesterol (LDLc)
time frame: 21 months
Mean Levels of High Density Lipoprotein Cholesterol (HDLc)
time frame: 21 months
Mean Levels of Very Low Density Lipoprotein (VLDL)
time frame: 21 months
Mean Levels of Total Cholesterol (TC)
time frame: 21 months
Mean Levels of Triglycerides (TG)
time frame: 21 months
Mean Levels of PCSK9
time frame: 21 months
Correlation analysis: Relating the strength of antibody responses to Lipid lowering effects
time frame: 21 months

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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.

Additional Information

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
Principal investigator Markus Zeitlinger, MD
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Affiris AG.