Homozygous Familial HypercholesterolemiaPhase 3NCT00730236
A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)
A Phase 3 study testing AEGR-733 in people with Homozygous Familial Hypercholesterolemia, run by Aegerion Pharmaceuticals, Inc. at 10 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Homozygous Familial Hypercholesterolemia
- What is being tested?
- AEGR-733
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 10 sitesin 4 countries
- Study dates
- Dec 2007to Oct 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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.
- Current use of corticosteroids or betaine
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
Italy4 sites
Medicina Interna Universitaria
Ferrara
Centro Universitario Dislipidemie
Milan
Dipartimento di Medicina Clinica e Della Patalogie Emergenti
Palermo, Sicily
Dipartimento di Clinica e Terapia Medica
Roma
United States2 sites
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Canada2 sites
Lipid Clinic and University of Montreal Community Genomic Medicine Center
Chicoutimi, Quebec, G7H 5H6
Robarts Research Institute
London, Ontario, N6A 5K8
South Africa2 sites
Cardiology Research
Bloemfontein, 9300
University of Capetown
Cape Town, 7925
About this study
Official title: A Phase III Study of Microsomal Triglyceride Transfer Protein (MTP) Inhibitor AEGR-733 in Patients With Homozygous Familial Hypercholesterolemia on Current Lipid-lowering Therapy
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.
Read the detailed description
Homozygous familial hypercholesterolemia (FH) is a serious life-threatening genetic disease. Total plasma cholesterol levels are generally over 500 mg/dl and markedly premature cardiovascular disease is the major consequence. Untreated, most patients develop atherosclerosis before age 20 and generally do not survive past age 30. The primary goal of therapy involves reducing cholesterol (specifically, LDL cholesterol) and preventing coronary artery disease. Unfortunately, patients with homozygous FH are minimally responsive or unresponsive to available drug therapy and thus there are limited treatment options. The current standard of care is LDL apheresis, a physical method of removing the plasma of LDL cholesterol which can transiently reduce cholesterol by more than 50%. However, there is rapid re-accumulation of LDL cholesterol in plasma, and therefore apheresis has to be repeated frequently (every 1-2 weeks) and requires 2 separate sites for IV access. Although anecdotally this procedure may delay the onset of atherosclerosis, it is laborious, expensive, and not readily available. Furthermore, although it is a procedure that is generally well tolerated, the fact that it needs frequent repetition and IV access can be challenging for many of these young patients. Therefore, there is a tremendous unmet medical need for new medical therapies for this orphan disease.
AEGR-733 is a novel oral therapeutic agent for hypercholesterolemia. Its mechanism involves inhibition of microsomal triglyceride transfer protein, resulting in a reduction of LDL cholesterol. Earlier studies in patients with homozygous FH reveal AEGR-733 is highly effective in lowering LDL cholesterol, yet long term safety and efficacy need to be established.
- Conditions
- Homozygous Familial Hypercholesterolemia
- Being tested
- AEGR-733
- Medical subject headings
- Homozygous Familial Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AEGR-733Drug
Also called lomitapide, BMS-201038
5-80 mg daily by mouth for 1.5 yrs
| Study group | Role | What they receive |
|---|---|---|
| AEGR-733 | Experimental | Not described Receives: Drug: AEGR-733 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Percent change from Baseline in LDL-C
Measured: Baseline and Week 26
Secondary outcomes (11)
Percent Change From Baseline in Total Cholesterol (TC)
Percent change from Baseline in TC
Measured: Baseline and Week 26
Percent Change From Baseline for Apolipoprotein B (Apo B)
Percent change from Baseline for Apo B
Measured: Baseline and Week 26
Percent Change From Baseline in Triglycerides
Percent change from Baseline in triglycerides
Measured: Baseline and Week 26
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)
Percent change from Baseline in HDL-C
Measured: Baseline and Week 26
Percent Change From Baseline in Non-HDL-C
Percent change from Baseline in non-HDL-C
Measured: Baseline and Week 26
Percent Change From Baseline in Apolipoprotein AI (Apo AI)
Percent change from Baseline in Apo AI
Measured: Baseline and Week 26
Absolute Change From Baseline in Hepatic Fat Percent
Absolute change from Baseline in hepatic fat percent
Measured: Baseline and Week 78
Absolute Change From Baseline in Alanine Aminotransferase (ALT)
Absolute change from Baseline in ALT
Measured: Baseline and Week 78
Absolute Change From Baseline in Aspartate Aminotransferase (AST)
Absolute change from Baseline in AST
Measured: Baseline and Week 78
Absolute Change From Baseline in Total Bilirubin
Absolute change from Baseline in total bilirubin
Measured: Baseline and Week 78
Absolute Change From Baseline in Weight
Absolute change from Baseline in weight
Measured: Baseline and Week 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2008 (estimated)
- Study startDec 2007
- Primary completionSep 2010
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Homozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aegerion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- FDA Office of Orphan Products Development
- Responsible party
- Sponsor
- Investigators
- Mark Sumeray, MD, Study director, Aegerion Pharmaceuticals, Inc.Marina Cuchel, MD, PhD, Principal investigator, Univerity of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00730236
- Sponsor's protocol ID
- AEGR-733-005 / UP1002
- Status last verified
- Jan 2013
- First submitted
- 6 Aug 2008
- Last updated
- 20 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 17215532Cuchel 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
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.
PubMed 36520008Averna 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.
PubMed 26723464Stefanutti 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.
PubMed 25897792
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study of Microsomal Triglyceride Transfer Protein (MTP) Inhibitor AEGR-733 in Patients With Homozygous Familial Hypercholesterolemia on Current Lipid-lowering Therapy
- ClinicalTrials.gov ID
- NCT00730236
- Acronym / sponsor ID
- AEGR-733-005 / UP1002
- Conditions
- Homozygous Familial Hypercholesterolemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Aegerion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- FDA Office of Orphan Products Development
- Study start
- Dec 2007
- Primary completion
- Sep 2010 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 8 Aug 2008 (estimated)
- Results
- Posted 22 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Homozygous familial hypercholesterolemia (FH) is a serious life-threatening genetic disease. Total plasma cholesterol levels are generally over 500 mg/dl and markedly premature cardiovascular disease is the major consequence. Untreated, most patients develop atherosclerosis before age 20 and generally do not survive past age 30. The primary goal of therapy involves reducing cholesterol (specifically, LDL cholesterol) and preventing coronary artery disease. Unfortunately, patients with homozygous FH are minimally responsive or unresponsive to available drug therapy and thus there are limited treatment options. The current standard of care is LDL apheresis, a physical method of removing the plasma of LDL cholesterol which can transiently reduce cholesterol by more than 50%. However, there is rapid re-accumulation of LDL cholesterol in plasma, and therefore apheresis has to be repeated frequently (every 1-2 weeks) and requires 2 separate sites for IV access. Although anecdotally this procedure may delay the onset of atherosclerosis, it is laborious, expensive, and not readily available. Furthermore, although it is a procedure that is generally well tolerated, the fact that it needs frequent repetition and IV access can be challenging for many of these young patients. Therefore, there is a tremendous unmet medical need for new medical therapies for this orphan disease.
AEGR-733 is a novel oral therapeutic agent for hypercholesterolemia. Its mechanism involves inhibition of microsomal triglyceride transfer protein, resulting in a reduction of LDL cholesterol. Earlier studies in patients with homozygous FH reveal AEGR-733 is highly effective in lowering LDL cholesterol, yet long term safety and efficacy need to be established.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AEGR-733 | Experimental | Drug: AEGR-733 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AEGR-733Also: lomitapide, BMS-2010385-80 mg daily by mouth for 1.5 yrs | Drug | AEGR-733 |
Primary outcome
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: Baseline and Week 26
Percent change from Baseline in LDL-C
11 secondary outcomes
Percent Change From Baseline in Total Cholesterol (TC)
Time frame: Baseline and Week 26
Percent Change From Baseline for Apolipoprotein B (Apo B)
Time frame: Baseline and Week 26
Percent Change From Baseline in Triglycerides
Time frame: Baseline and Week 26
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)
Time frame: Baseline and Week 26
Percent Change From Baseline in Non-HDL-C
Time frame: Baseline and Week 26
Percent Change From Baseline in Apolipoprotein AI (Apo AI)
Time frame: Baseline and Week 26
Absolute Change From Baseline in Hepatic Fat Percent
Time frame: Baseline and Week 78
Absolute Change From Baseline in Alanine Aminotransferase (ALT)
Time frame: Baseline and Week 78
Absolute Change From Baseline in Aspartate Aminotransferase (AST)
Time frame: Baseline and Week 78
Absolute Change From Baseline in Total Bilirubin
Time frame: Baseline and Week 78
Absolute Change From Baseline in Weight
Time frame: Baseline and Week 78
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17215532Cuchel 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.
- Results publicationCuchel 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
- Derived from this study: PubMed 36520008Larrey 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.
- Derived from this study: PubMed 26723464Averna 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.
- Derived from this study: PubMed 25897792Stefanutti 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Sumeray, MD study director
Aegerion Pharmaceuticals, Inc.
Marina Cuchel, MD, PhD principal investigator
Univerity of Pennsylvania
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AEGR-733 in people with Homozygous Familial Hypercholesterolemia, run by Aegerion Pharmaceuticals, Inc. at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy, United States, Canada, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) (time frame: Baseline and Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00730236, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2018.