Alirocumab in Patients on a Stable Dialysis Regimen

Hypercholesterolemia Clinical Trial

Official title:

A Phase III Trial to Evaluate the Efficacy and Safety of Biweekly Alirocumab in Patients on a Stable Dialysis Regimen: The Alidial Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03480568
• Other study ID #: 018-038
• Status: Recruiting
• Phase: Phase 3
• Start date: May 1, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: January 2020
• Source: Baylor Research Institute
• Contact: Cara East, MD
• Phone: 214-820-2273
• Email: cara.east[@]bswhealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

12-week study of the efficacy and safety of alirocumab in patients maintained stably on hemodialysis or peritoneal dialysis. Measures of cholesterol levels, drug levels, PCSK9 levels, routine chemistry and cell counts, and biomarkers will be obtained at baseline and at weeks 4, 8, 10 and 12 weeks. Safety events will be obtained throughout the study.

Description:

Primary objective: The objective of this trial is to demonstrate the efficacy of alirocumab 150 mg every 2 weeks over 12 weeks on cholesterol levels.

Secondary objective: To assess the safety of treating chronic dialysis patients with alirocumab 150 mg subcutaneously every 2 weeks for 12 weeks.

Secondary objective: To demonstrate the efficacy of alirocumab 150 mg every 2 weeks over 12 weeks on biomarkers.

Exploratory objective: To assess alirocumab drug levels in subjects maintained on hemodialysis and peritoneal dialysis.

Methodology: Open-label, nonrandomized study

Number of patients Ten patients maintained on stable hemodialysis for a minimum of 3 months and ten patients maintained on stable peritoneal dialysis for a minimum of 3 months

Test product: alirocumab 150 mg

Mode of administration: administered subcutaneously

Dosing interval: every 2 weeks

Duration of treatment: 12 weeks

Primary endpoint: Levels of LDL-cholesterol at 12 weeks

Secondary endpoints: Levels of total cholesterol, triglycerides, apoprotein B, Cystatin-C, fibrinogen, hsCRP, IL-6, NGAL, NT-proBNP, soluble CD40 ligand, troponin T, VCAM

Safety criteria: Adverse events, Incidence and intensity of AE, including serious AE (SAE), Withdrawal from study medication due to AE, Clinical relevant new findings or worsening of existing conditions physical examination, Clinically relevant changes in laboratory measurements from baseline

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Male or female patients, ages 18 to 80 years.

2. Written informed consent will be obtained before any study assessment is performed.

3. Diagnosis of end-stage renal disease, maintained on dialysis, without dialysis complications, for at least 3 months.

4. Patients may or may not have a diagnosis of atherosclerotic disease, such as a history of myocardial infarction (MI), cardiac percutaneous coronary intervention (PCI), coronary artery bypass (CABG) surgery, atherosclerotic transient ischemic attack (TIA) or cerebrovascular attack (CVA), or peripheral arterial disease (PAD).

5. A total of 20 patients will be enrolled, 10 patients on hemodialysis and 10 patients on peritoneal dialysis.

Exclusion Criteria:

1. LDL-cholesterol level of < 70 mg/dL.

2. Any contraindication to subcutaneous injections.

3. Patients on statin and/or ezetimibe therapy will have their cholesterol-lowering therapy continued as is without change during the time of the study.

4. History of any allergy or intolerance to the study drug or drugs of the same class.

5. A history of MI, PCI, CABG surgery, TIA, CVA, or PAD events within 3 months of enrollment.

6. History of malignant cancer within the past 3 years, excepting basal cell skin cancer or cervical cancer in situ.

7. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of the drug and for 2 weeks after the last injection of the drug. Highly effective methods of contraception include:

1. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

2. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.

3. Male sterilization (at least 6 months prior to enrollment). For female patients in the study, the vasectomized male partner should be the sole partner for that patient.

4. Use of oral (estrogen and/or progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.

5. In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

6. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before enrollment.

8. Pregnant or lactating women.

9. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or extraction of study drug, at investigator's discretion.

10. History or evidence of drug or alcohol abuse within the last 12 months.

11. Patients considered unsuitable for the study, including patients with psychiatric, behavioral or cognitive disorders, sufficient to interfere with the patient's ability to understand and comply with the protocol instructions or follow-up procedures.

Related Conditions & MeSH terms

• Atherosclerotic Disease
• Hemodialysis
• Hypercholesterolemia
• Peritoneal Dialysis

Intervention

Drug:
• Alirocumab 150 MG/ML [Praluent]
Cholesterol-lowering therapy

Locations

Country	Name	City	State
United States	Baylor Soltero CV Research	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor Research Institute	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (13)

6. KDIGO clinical practice guideline for lipid management in chronic kidney disease. Kidney Int Suppl. 2013;3:259-286.

Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellström B — View Citation

Chapter 2: Pharmacological cholesterol-lowering treatment in adults. Kidney Int Suppl (2011). 2013 Nov;3(3):271-279. — View Citation

Collins AJ, Foley RN, Herzog C, Chavers BM, Gilbertson D, Ishani A, Kasiske BL, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Li Q, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Da — View Citation

Everett BM, Smith RJ, Hiatt WR. Reducing LDL with PCSK9 Inhibitors--The Clinical Benefit of Lipid Drugs. N Engl J Med. 2015 Oct 22;373(17):1588-91. doi: 10.1056/NEJMp1508120. Epub 2015 Oct 7. — View Citation

Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, Chae DW, Chevaile A, Cobbe SM, Grönhagen-Riska C, De Lima JJ, Lins R, Mayer G, McMahon AW, Parving HH, Remuzzi G, Samuelsson O, Sonkodi S, Sci D, Süleymanlar G, Tsakiris D, Tesar V — View Citation

Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Inverse association between lipid levels and mortality in men with chronic kidney disease who are not yet on dialysis: effects of case mix and the malnutrition-inflammation-cachexia syndrome. J Am Soc Nephrol. 20 — View Citation

Krane V, Schmidt KR, Gutjahr-Lengsfeld LJ, Mann JF, März W, Swoboda F, Wanner C; 4D Study Investigators (the German Diabetes and Dialysis Study Investigators). Long-term effects following 4 years of randomized treatment with atorvastatin in patients with — View Citation

März W, Genser B, Drechsler C, Krane V, Grammer TB, Ritz E, Stojakovic T, Scharnagl H, Winkler K, Holme I, Holdaas H, Wanner C; German Diabetes and Dialysis Study Investigators. Atorvastatin and low-density lipoprotein cholesterol in type 2 diabetes melli — View Citation

Rogacev KS, Pinsdorf T, Weingärtner O, Gerhart MK, Welzel E, van Bentum K, Popp J, Menzner A, Fliser D, Lütjohann D, Heine GH. Cholesterol synthesis, cholesterol absorption, and mortality in hemodialysis patients. Clin J Am Soc Nephrol. 2012 Jun;7(6):943- — View Citation

Shoji T. Serum lipids and prevention of atherosclerotic cardiovascular events in hemodialysis patients. Clin Exp Nephrol. 2014 Apr;18(2):257-60. doi: 10.1007/s10157-013-0871-z. Epub 2013 Sep 27. Review. — View Citation

van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey A, de Jong P, Gansevoort RT; Chronic Kidney Disease Prognosis Consortium, van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey AS, de Jong PE, Gansevoort RT, Levey A, El- — View Citation

Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, Ritz E; German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005 Jul 21;353(3):238-48. Erratum in: N Engl — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in PCSK9 levels	Efficacy	Baseline, 4, 8, 10, 12 weeks
Other	Change in alirocumab drug levels	Efficacy	Baseline, 4, 8, 10, 12 weeks
Primary	Change in LDL cholesterol levels	Efficacy	Baseline, 4 ,8, 12 weeks
Secondary	Change in HDL-cholesterol levels	Efficacy	Baseline, 12 weeks
Secondary	Change in apoprotein B levels	Efficacy	Baseline, 4, 8, 12 weeks

External Links

•   1. Kidney disease statistics for the United States. Kidney.niddk.nih.gov.
•   15. PCSK9 gene—genetics home reference. Ghr.nlm.nih.gov/gene/PCSK9.
•   2. Statistics, The Kidney Project. Pharm.ucsf.edu/kidney/need/statistics.