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

NCT ID: NCT02508896

Last Updated: 2017-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2017-08-31

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.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: EXPERIMENTAL

AFFITOPE® AT04A+adjuvant

Intervention Type: BIOLOGICAL

subcutaneous injection

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

Group Type: EXPERIMENTAL

AFFITOPE® AT06A+adjuvant

Intervention Type: BIOLOGICAL

subcutaneous injection

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

Group Type: PLACEBO_COMPARATOR

Adjuvant without active component

Intervention Type: BIOLOGICAL

subcutaneous injection

Interventions

AFFITOPE® AT04A+adjuvant

subcutaneous injection

Intervention Type: BIOLOGICAL

AFFITOPE® AT06A+adjuvant

subcutaneous injection

Intervention Type: BIOLOGICAL

Adjuvant without active component

subcutaneous injection

Intervention Type: BIOLOGICAL

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: collaborator

Affiris AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Markus Zeitlinger, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, , Austria

Countries

Austria

References

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.

Reference Type: DERIVED

PMID: 33969434 (View on PubMed)

Other Identifiers

2015-001719-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AFFiRiS 012

Identifier Type: -

Identifier Source: org_study_id