Alirocumab in Patients on a Stable Dialysis Regimen

NCT03480568 | Unknown Phase 3 FDA Drug

• 1 other identifier: 018-038
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hemodialysis; Peritoneal Dialysis; Hypercholesterolemia; Atherosclerotic Disease

Keywords

Alirocumab

Outcome Measures

Primary Outcomes (1)

• Change in LDL cholesterol levels

  Efficacy

  Baseline, 4 ,8, 12 weeks

Secondary Outcomes (2)

• Change in HDL-cholesterol levels

  Baseline, 12 weeks

• Change in apoprotein B levels

  Baseline, 4, 8, 12 weeks

Other Outcomes (2)

• Change in PCSK9 levels

  Baseline, 4, 8, 10, 12 weeks

• Change in alirocumab drug levels

  Baseline, 4, 8, 10, 12 weeks

Study Arms (1)

alirocumab

EXPERIMENTAL

Alirocumab 150 mg q 2 weeks for 12 weeks

Drug: Alirocumab 150 MG/ML [Praluent]

Interventions

Alirocumab 150 MG/ML [Praluent] DRUG

Cholesterol-lowering therapy

alirocumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, ages 18 to 80 years.
• Written informed consent will be obtained before any study assessment is performed.
• Diagnosis of end-stage renal disease, maintained on dialysis, without dialysis complications, for at least 3 months.
• 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).
• A total of 20 patients will be enrolled, 10 patients on hemodialysis and 10 patients on peritoneal dialysis.

You may not qualify if:

• LDL-cholesterol level of \< 70 mg/dL.
• Any contraindication to subcutaneous injections.
• Patients on statin and/or ezetimibe therapy will have their cholesterol-lowering therapy continued as is without change during the time of the study.
• History of any allergy or intolerance to the study drug or drugs of the same class.
• A history of MI, PCI, CABG surgery, TIA, CVA, or PAD events within 3 months of enrollment.
• History of malignant cancer within the past 3 years, excepting basal cell skin cancer or cervical cancer in situ.
• 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:
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Pregnant or lactating women.
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or extraction of study drug, at investigator's discretion.

Sponsors & Collaborators

• Baylor Research Institute: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Baylor Soltero CV Research

Dallas, Texas, 75226, United States

RECRUITING

Related Publications (14)

• 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, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers PW, Agodoa L. Excerpts from the US Renal Data System 2009 Annual Data Report. Am J Kidney Dis. 2010 Jan;55(1 Suppl 1):S1-420, A6-7. doi: 10.1053/j.ajkd.2009.10.009. No abstract available.

  PMID: 20082919 RESULT

• 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-Nahas M, Eckardt KU, Kasiske BL, Ninomiya T, Chalmers J, Macmahon S, Tonelli M, Hemmelgarn B, Sacks F, Curhan G, Collins AJ, Li S, Chen SC, Hawaii Cohort KP, Lee BJ, Ishani A, Neaton J, Svendsen K, Mann JF, Yusuf S, Teo KK, Gao P, Nelson RG, Knowler WC, Bilo HJ, Joosten H, Kleefstra N, Groenier KH, Auguste P, Veldhuis K, Wang Y, Camarata L, Thomas B, Manley T. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int. 2011 Jun;79(12):1341-52. doi: 10.1038/ki.2010.536. Epub 2011 Feb 9.

  PMID: 21307840 RESULT

• Rogacev KS, Pinsdorf T, Weingartner O, Gerhart MK, Welzel E, van Bentum K, Popp J, Menzner A, Fliser D, Lutjohann D, Heine GH. Cholesterol synthesis, cholesterol absorption, and mortality in hemodialysis patients. Clin J Am Soc Nephrol. 2012 Jun;7(6):943-8. doi: 10.2215/CJN.05170511. Epub 2012 Mar 29.

  PMID: 22461539 RESULT

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

  RESULT

• Chapter 2: Pharmacological cholesterol-lowering treatment in adults. Kidney Int Suppl (2011). 2013 Nov;3(3):271-279. doi: 10.1038/kisup.2013.34. No abstract available.

  PMID: 25019001 RESULT

• 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. 2007 Jan;18(1):304-11. doi: 10.1681/ASN.2006060674. Epub 2006 Dec 13.

  PMID: 17167114 RESULT

• 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.

  PMID: 24072417 RESULT

• Wanner C, Krane V, Marz 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. doi: 10.1056/NEJMoa043545.

  PMID: 16034009 RESULT

• Marz 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 mellitus patients on hemodialysis. Clin J Am Soc Nephrol. 2011 Jun;6(6):1316-25. doi: 10.2215/CJN.09121010. Epub 2011 Apr 14.

  PMID: 21493741 RESULT

• Krane V, Schmidt KR, Gutjahr-Lengsfeld LJ, Mann JF, Marz 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 type 2 diabetes mellitus on hemodialysis. Kidney Int. 2016 Jun;89(6):1380-7. doi: 10.1016/j.kint.2015.12.033. Epub 2016 Feb 17.

  PMID: 26924051 RESULT

• Fellstrom BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, Chae DW, Chevaile A, Cobbe SM, Gronhagen-Riska C, De Lima JJ, Lins R, Mayer G, McMahon AW, Parving HH, Remuzzi G, Samuelsson O, Sonkodi S, Sci D, Suleymanlar G, Tsakiris D, Tesar V, Todorov V, Wiecek A, Wuthrich RP, Gottlow M, Johnsson E, Zannad F; AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009 Apr 2;360(14):1395-407. doi: 10.1056/NEJMoa0810177. Epub 2009 Mar 30.

  PMID: 19332456 RESULT

• 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, Fellstrom B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Gronhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R; SHARP Investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92. doi: 10.1016/S0140-6736(11)60739-3. Epub 2011 Jun 12.

  PMID: 21663949 RESULT

• 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. No abstract available.

  PMID: 26444323 RESULT

• East C, Bass K, Mehta A, Rahimighazikalayed G, Zurawski S, Bottiglieri T. Alirocumab and Lipid Levels, Inflammatory Biomarkers, Metabolomics, and Safety in Patients Receiving Maintenance Dialysis: The ALIrocumab in DIALysis Study (A Phase 3 Trial to Evaluate the Efficacy and Safety of Biweekly Alirocumab in Patients on a Stable Dialysis Regimen). Kidney Med. 2022 May 20;4(7):100483. doi: 10.1016/j.xkme.2022.100483. eCollection 2022 Jul.

  PMID: 35801187 DERIVED

Related Links

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

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Cara East, MD

  Baylor Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cara East, MD

CONTACT

214-820-2273; cara.east@bswhealth.org

Merielle Boatman

CONTACT

214-820-2273; merielle.boatman@bswhealth.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, nonrandomized study

Study Record Dates

• First Submitted: March 1, 2018
• First Posted: March 29, 2018
• Study Start: May 1, 2018
• Primary Completion: August 31, 2020
• Study Completion: December 31, 2020
• Last Updated: February 12, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: within 6 weeks of request

Locations

US (1)