A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)

NCT00730236 | Completed Phase 3 Results DMC

• 1 other identifier: AEGR-733-005 / UP1002
• Study Type: interventional
• Target: 29
• Locations: 4 countries
• Sites: 10

Brief Summary

The goal of this trial is to study the effects of AEGR-733 on LDL cholesterol, other lipids as well as measures of safety over the long-term.

Conditions

Homozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)

  Percent change from Baseline in LDL-C

  Baseline and Week 26

Secondary Outcomes (11)

• Percent Change From Baseline in Total Cholesterol (TC)

  Baseline and Week 26

• Percent Change From Baseline for Apolipoprotein B (Apo B)

  Baseline and Week 26

• Percent Change From Baseline in Triglycerides

  Baseline and Week 26

• Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)

  Baseline and Week 26

• Percent Change From Baseline in Non-HDL-C

  Baseline and Week 26

Study Arms (1)

AEGR-733

EXPERIMENTAL

Drug: AEGR-733

Interventions

AEGR-733 DRUG

5-80 mg daily by mouth for 1.5 yrs

Also known as: lomitapide, BMS-201038

AEGR-733

Eligibility Criteria

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

You may qualify if:

• Males and females at least 18 years of age
• Diagnosis of functional homozygous FH by at least one (a-c) of the following clinical criteria:
• documented functional mutation(s) in both LDL receptor alleles or alleles known to affect LDL receptor functionality OR
• skin fibroblast LDL receptor activity less than 20% normal OR
• untreated TC greater than 500 mg/dL AND TG less then 300 mg/dL AND both parents have documented TC greater than 250 mg/dL
• Concurrent lipid lowering medication/apheresis must be stable for at least 6 weeks before the baseline visit and must remain stable for the first 26 weeks.
• Body weight at least 40 kg and less than 136 kg
• Negative screening pregnancy test if female of child-bearing potential (females of child-bearing potential and all males must be following a medically accepted form of contraception)
• Subjects must be willing to comply with all study-related procedures

You may not qualify if:

• Uncontrolled hypertension
• History of chronic renal insufficiency
• History of biopsy proven cirrhosis or abnormal LFTs at screening (AST or ALT greater than 2 x upper limit of normal and/or Total Bilirubin greater than or equal to 1.5 mg/dl unless patient has unconjugated hyperbilirubinemia due to Gilbert's syndrome)
• Chronic hepatitis B or chronic hepatitis C
• Any major surgical procedure occurring less than 3 months prior to the screening visit
• Cardiac insufficiency defined by the NYHA classification as functional Class III or Class IV
• Previous organ transplantation
• History of a non-skin malignancy within the previous 3 years
• Male subjects reporting more than 2 drinks per day or females reporting more than 1 drink per day (1 drink= 12 oz beer, 1 oz hard liquor, 5 oz wine).
• Participation in an investigational drug study within 6 weeks prior to the screening visit
• Known significant gastrointestinal bowel disease or malabsorption such as inflammatory bowel disease or chronic pancreatitis requiring use of daily pancreatic enzymes.
• Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.
• Certain prohibited medications known to be potentially hepatotoxic, especially those that can induce microvesicular or macrovesicular steatosis. These include but are not limited to: accutane, amiodarone, heavy acetaminophen use (4g/day greater than 3 x q week), methotrexate, tetracyclines,and tamoxifen
• Documented diagnosis of any of the following pulmonary conditions: Asthma, Chronic Obstructive Pulmonary Disease (COPD), Idiopathic pulmonary fibrosis
• Documented diagnosis of any of the following liver diseases: Nonalcoholic Steatohepatitis, Alcoholic liver disease, Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, hemochromatosis, alpha 1 anti-trypsin deficiency.

Sponsors & Collaborators

• Aegerion Pharmaceuticals, Inc.: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (10)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Robarts Research Institute

London, Ontario, N6A 5K8, Canada

Location

Lipid Clinic and University of Montreal Community Genomic Medicine Center

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Dipartimento di Medicina Clinica e Della Patalogie Emergenti

Palermo, Sicily, Italy

Location

Medicina Interna Universitaria

Ferrara, Italy

Location

Centro Universitario Dislipidemie

Milan, Italy

Location

Dipartimento di Clinica e Terapia Medica

Roma, Italy

Location

Cardiology Research

Bloemfontein, 9300, South Africa

Location

University of Capetown

Cape Town, 7925, South Africa

Location

Related Publications (5)

• Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007 Jan 11;356(2):148-56. doi: 10.1056/NEJMoa061189.

  PMID: 17215532 BACKGROUND

• Cuchel M, Meagher E, Marais AD, et.al. Abstract 1077: A phase III study of microsomal triglyceride transfer protein inhibitor lomitapide (AEGR-733) in patients with homozygous familial hypercholesterolemia: interim results at 6 months. Circulation, Nov 2009; 120: S441

  RESULT

• Larrey D, D'Erasmo L, O'Brien S, Arca M; Italian Working Group on Lomitapide. Long-term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia. Liver Int. 2023 Feb;43(2):413-423. doi: 10.1111/liv.15497. Epub 2022 Dec 30.

  PMID: 36520008 DERIVED

• Averna M, Cefalu AB, Stefanutti C, Di Giacomo S, Sirtori CR, Vigna G. Individual analysis of patients with HoFH participating in a phase 3 trial with lomitapide: The Italian cohort. Nutr Metab Cardiovasc Dis. 2016 Jan;26(1):36-44. doi: 10.1016/j.numecd.2015.11.001. Epub 2015 Nov 11.

  PMID: 26723464 DERIVED

• Stefanutti C, Blom DJ, Averna MR, Meagher EA, Theron Hd, Marais AD, Hegele RA, Sirtori CR, Shah PK, Gaudet D, Vigna GB, Sachais BS, Di Giacomo S, du Plessis AM, Bloedon LT, Balser J, Rader DJ, Cuchel M; Phase 3 HoFH Lomitapide Study Investigators. The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - a post-hoc analysis of a Phase 3, single-arm, open-label trial. Atherosclerosis. 2015 Jun;240(2):408-14. doi: 10.1016/j.atherosclerosis.2015.03.014. Epub 2015 Mar 14.

  PMID: 25897792 DERIVED

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

BMS201038

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Mark Sumeray, MD, Chief Medical Officer
• Organization: Aegerion Pharmaceuticals

msumeray@aegerion.com

617-500-7867

Study Officials

• Mark Sumeray, MD

  Aegerion Pharmaceuticals, Inc.

  STUDY DIRECTOR

• Marina Cuchel, MD, PhD

  Univerity of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 6, 2008
• First Posted: August 8, 2008
• Study Start: December 1, 2007
• Primary Completion: September 1, 2010
• Study Completion: October 1, 2011
• Last Updated: March 20, 2018
• Results First Posted: February 22, 2013

Record last verified: 2013-01

Locations

US (2); ZA (2); CA (2); IT (4)