NCT02508896

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
72

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jul 2015

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2015

Completed
23 days until next milestone

First Submitted

Initial submission to the registry

July 24, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 27, 2015

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2017

Completed
Last Updated

October 20, 2017

Status Verified

October 1, 2017

Enrollment Period

10 months

First QC Date

July 24, 2015

Last Update Submit

October 19, 2017

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

  • Occurence of any Serious Adverse Event (SAE)

    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

    21 months

Secondary Outcomes (9)

  • Immunological activity of AFFITOPE® AT04A: Titer of vaccination-induced antibodies

    21 months

  • Immunological activity of AFFITOPE® AT06A: Titer of vaccination-induced antibodies

    21 months

  • Mean Levels of Low Density Lipoprotein Cholesterol (LDLc)

    21 months

  • Mean Levels of High Density Lipoprotein Cholesterol (HDLc)

    21 months

  • Mean Levels of Very Low Density Lipoprotein (VLDL)

    21 months

  • +4 more secondary outcomes

Study Arms (3)

AFFITOPE® AT04A+adjuvant

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

Biological: AFFITOPE® AT04A+adjuvant

AFFITOPE® AT06A+adjuvant

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

Biological: AFFITOPE® AT06A+adjuvant

Adjuvant without active component

PLACEBO COMPARATOR

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

Interventions

AFFITOPE® AT04A+adjuvantBIOLOGICAL

subcutaneous injection

AFFITOPE® AT04A+adjuvant
AFFITOPE® AT06A+adjuvantBIOLOGICAL

subcutaneous injection

AFFITOPE® AT06A+adjuvant
Adjuvant without active componentBIOLOGICAL

subcutaneous injection

Adjuvant without active component

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

Location

Related Publications (1)

  • Zeitlinger M, Bauer M, Reindl-Schwaighofer R, Stoekenbroek RM, Lambert G, Berger-Sieczkowski E, Lagler H, Oesterreicher Z, Wulkersdorfer B, Luhrs P, Galabova G, Schwenke C, Mader RM, Medori R, Landlinger C, Kutzelnigg A, Staffler G. A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9. Eur J Clin Pharmacol. 2021 Oct;77(10):1473-1484. doi: 10.1007/s00228-021-03149-2. Epub 2021 May 10.

    PMID: 33969434DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

HyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutic AidsPharmaceutical PreparationsSpecialty Uses of ChemicalsChemical Actions and Uses

Study Officials

  • Markus Zeitlinger, MD

    Medical University of Vienna

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 24, 2015

First Posted

July 27, 2015

Study Start

July 1, 2015

Primary Completion

May 1, 2016

Study Completion

August 31, 2017

Last Updated

October 20, 2017

Record last verified: 2017-10

Locations

AU(1)