Effect of Alirocumab on Lipoprotein(a) (Lp(a)) Metabolism in Subjects with Moderate to High Risk of Heart Disease

• Register: ANZCTR
• Last refreshed on: 28 October 2019
• Main ID: ACTRN12617000401358
• Date of registration: 17/03/2017
• Prospective Registration: No
• Primary sponsor: Linear Clinical Research Ltd.
• Public title: Effect of Alirocumab on Lipoprotein(a) (Lp(a)) Metabolism in Subjects with Moderate to High Risk of Heart Disease
• Scientific title: Mechanism of the Effect of Alirocumab on Lipoprotein(a) Metabolism in Subjects with Inherited Elevation in Lipoprotein(a)
• Date of first enrolment: 11/01/2017
• Target sample size: 21
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12617000401358.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Pharmacodynamics;
• Phase: Phase 2

Countries of recruitment

Australia

Contacts

• Name: Prof Gerald Watts

• Name: Prof Gerald Watts

Key inclusion & exclusion criteria

Inclusion criteria: 1. Caucasian and non-caucasian
2. Aged 18-75 years inclusive, male or female
3. Men and women on maximally tolerated high potency stains with elevated plasma Lp(a) concentrations [equal or more than 0.6 g/L] who have moderate-to-high cardiovascular disease (CVD) risk based on the Australian National Vascular Disease Prevention Alliance (NVDPA) Guidelines for management of absolute cardiovascular disease risk (including documented and/or family history of CVD or CVD risk equivalent including documented history of other clinical atherosclerotic disease(s) i.e. peripheral artery disease, clinically significant carotid artery disease, abdominal aortic aneurysm)
For the purposes of this project, documented CVD includes: documentation of a history of myocardial infarction [MI], coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or alternative revascularization procedure [e.g. atherectomy/stent], coronary artery disease documented by exercise or non-exercise stress test and/or clinically significant carotid artery disease documented by angiography, carotid ultrasonography, or any other accepted cardiac computed imaging technique
4. Participants will be of stable weight and maintaining a guideline recommended heart healthy diet (lower saturated fat, higher complex carbohydrate and lower salt content)
5. Participants will be on concurrent aspirin therapy, 75 mg – 300 mg orally once daily, for at least one week prior to Day 1 and continue for the duration of the study
Exclusion criteria: 1. Cardiovascular events in the past 6-months
2. History of venous thromboembolism and/or pulmonary embolism
3. Low-density lipoprotein cholesterol equal to or less than 1.0 mmol/L
4. Participation in another clinical trial involving a PCSK9 monoclonal antibody
5. Type 1 Diabetes Mellitus
6. Type 2 Diabetes Mellitus
7. Secondary hyperlipidaemia
8. Renal disease (creatinine >130 micro mol/L, including proteinuria, nephrotic syndrome)
9. Hepatic dysfunction (AST or ALT > 5x ULN)
10. Current anaemia or past history of significant anaemia e.g. haemolytic anaemia (Hb must be >125 g/L to be eligible)
11. Haematological disorders
12. Recent history of haemorrhage or donation of blood within the 3 months prior to screening
13. Women who are on hormone replacement therapy
14. Positive laboratory screening result for HIV, Hepatitis B or C
15. Current smoker
16. Psychiatric illness (participants who are stable on treatment for depression or anxiety are eligible)
17. Alcohol excess (>30 g/day)
18. Hypersensitivity or contraindicating co-morbidities to Aspirin
19. Lipid-lowering therapies that are known to have major effects on plasma Lp(a) levels e.g. niacin, high dose fish oils (equal or more than 4 g/day)
20. Active auto-immune or vasculitic disorders
21. Likelihood of not completing the study as per judgement of investigator
22. Of Japanese and South East Asian decent
23. Women who are pregnant and / or not using a highly effective method of contraception
24. People highly dependent on medical care (i.e. unstable clinical status requiring frequent ambulatory or inpatient care)
25. People with a cognitive impairment, an intellectual disability or a mental illness
26. People whose primary language is other than English (LOTE) who will not be able to provide informed consent
27. Known hypersensitivity to monoclonal antibody or any component of the drug product
28. Donated blood within 3 months prior to Day 1



Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cardiovascular Disease (CVD);
Cardiovascular Disease (CVD)

Cardiovascular - Coronary heart disease

Intervention(s)

A 12-week (treatment period) single-arm, open-label, pre- and post-designed pilot study of the effect of Alirocumab (two-weekly subcutaneously injected dose of 150 mg for a total of 6 doses) on plasma Lp(a) concentration and metabolism in 21 patients with inherited high plasma Lp(a). The CVD risk (low or moderate-to-high) of participants will be determined based on the Australian National Vascular Disease Prevention Alliance (NVDPA) Guidelines for management of absolute cardiovascular disease risk.

Primary Outcome(s)

Lp(a) plasma levels will be assessed in patients with moderate-to-high risk of CVD

[Lp(a) levels will be assessed at baseline and at week 18 after intervention commencement

]

Secondary Outcome(s)

Intermediate-density lipoprotein (IDL) will be assessed in plasma[Baseline and at week 18 (visits 14 & 18) after intervention

Clarification:
After intervention, during week 18, participants visit clinic 5 days in a row (visit 14, 15, 16, 17, and 18). This time point occurs after intervention, during week 18 on visit numbers 14 and 18 (not weeks). ]

An assessment of the plasma lipid and lipoprotein profile, including Lp(a) and apo(a), 3 – 8 months after the cessation of the intervention trial has been added.
[Addition of follow-up visit 3 – 8 months after cessation of the intervention trial]

Low-density lipoprotein (LDL) will be assessed in plasma[Baseline and at week 18 (visits 14 & 18) after intervention

Clarification:
After intervention, during week 18, participants visit clinic 5 days in a row (visit 14, 15, 16, 17, and 18). This time point occurs after intervention, during week 18 on visit numbers 14 and 18 (not weeks). ]

Indices of biodiversity of gut microbiota in stool samples will be assessed[Baseline and at week 18 (once only on any visit including 15, 16, 17 or 18) after intervention

Clarification:
This time point can occur anytime during week 18, but after visit 14, So, participant would attend clinic 4 days in a row for study visits 15, 16, 17 and 18 after intervention and participants would bring stool sample on one of these visits (not weeks). ]

ApoB-100 concentrations will be assessed in plasma[Baseline and at week 18 (visits 14 & 18) after intervention

Clarification:
After intervention, during week 18, participants visit clinic 5 days in a row (visit 14, 15, 16, 17, and 18). This time point occurs after intervention, during week 18 on visit numbers 14 and 18 (not weeks). ]

High-density lipoprotein (HDL) will be assessed in plasma[Baseline and at week 18 (visits 14 & 18) after intervention

Clarification:
After intervention, during week 18, participants visit clinic 5 days in a row (visit 14, 15, 16, 17, and 18). This time point occurs after intervention, during week 18 on visit numbers 14 and 18 (not weeks). ]

Very-low density lipoprotein (VLDL) in plasma will be assessed

[Baseline and at week 18 after intervention commencement

]

Secondary ID(s)

LPS14508

Source(s) of Monetary Support

Regeneron Pharmaceuticals Inc

Ethics review

Status: Approved
Approval date:
Contact:

Bellberry Human Research Ethics Comittee

Results

• Results available: Yes
• Date Posted: 21/10/2019
• Date Completed: 08/07/2019