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

Affiris

Status and phase: Completed; Phase 1

Conditions: Hypercholesterolemia

Treatments: Biological: AFFITOPE® AT04A+adjuvant; Biological: AFFITOPE® AT06A+adjuvant; Biological: Adjuvant without active component

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02508896

AFFiRiS 012

2015-001719-11 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 72 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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72 participants in 3 patient groups, including a placebo group

AFFITOPE® AT04A+adjuvant

Experimental group

Description:

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

Treatment:

Biological: AFFITOPE® AT04A+adjuvant

AFFITOPE® AT06A+adjuvant

Experimental group

Description:

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

Treatment:

Biological: AFFITOPE® AT06A+adjuvant

Adjuvant without active component

Placebo Comparator group

Description:

3 injections of Placebo once every 4 weeks and 1 boost immunization which will be applied one year after the 3rd immunization

Treatment:

Biological: Adjuvant without active component