- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02472535
Study to Evaluate the Effects of MBX-8025 in Patients With HoFH
A 12-week, Open-label, Dose-escalating, Phase 2 Study to Evaluate the Effects of MBX-8025 in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
Study Overview
Status
Conditions
Detailed Description
Open-label, single arm, non-controlled, dose ascending (50 mg/day, 100 mg/day and 200 mg/day) with three consecutive dose escalation periods.
After signing an informed consent subject will enter a screening period and a run-in stabilization period. At the end of run-in period patients will enter treatment phase. MBX-8025 in ascending doses (50 mg, 100 mg, and 200 mg) will be given within three consecutive 4 weeks periods, for a total of 12 weeks. At the end of treatment, subjects will enter a follow-up period.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Quebec
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Chicoutimi, Quebec, Canada, G7H 7K9
- Ecogene-21
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Montreal, Quebec, Canada, H1T 1C8
- Montreal Heart Institute
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Paris, France, 75 013
- Endocrinologie metabolisme et prevention cardiovasulaire, Institut E3M et IHU cardiometabolique (ICAN), Hôpital Pitié Salpêtrière
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Nijmegen, Netherlands, 6525 GA
- Radbound UMC
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Oslo, Norway, N-0373
- Lipidklinikken, Oslo Universitetssykehus
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
- Male or female with HoFH confirmed by genotype (two mutant alleles at the LDL-Receptor (LDL-R) gene locus or double heterozygotes LDL-R/Apo-B).
- 18 years of age or older.
- Existing lipid lowering therapies (statins, cholesterol absorption inhibitors, bile acid sequestrants, nicotinic acid and their combinations, low-density lipoprotein (LDL) LDL-C apheresis) on a stable regimen for at least four weeks before screening visit.
- Stable lipid lowering diet compatible with a Step I diet of the American Heart Association (AHA).
- Fasting LDL-C ≥ 4.8 mmol/L (≥ 185.6 mg/dL) during screening.
- For females or males of reproductive potential, use of at least one barrier contraceptive and a second effective birth control method during the study and for at least two weeks after the last dose.
Exclusion Criteria:
- Treatment with lomitapide or mipomersen within two months of screening.
- Heart Failure (HF) with New York Heart Association (NYHA) class III and class IV or a Left ventricular ejection fraction (LVEF) of less than 30%.
- Uncontrolled cardiac arrhythmia during the past three months of screening.
- Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke during the past three months of screening.
- Planned cardiac surgery, or planned revascularization, in the next four months.
- Uncontrolled hypertension.
- Aspartate transaminase (AST) or Alanine transaminase (ALT) ≥ 3 times the Upper Limit of Normal (ULN).
- Unexplained creatine kinase (CK) ≥ 5 times the upper limit of normal (ULN).
- For females, pregnancy or breast-feeding.
- Any other condition(s) that would compromise the safety of the patient or compromise the quality of the clinical study as judged by the Investigator and/or Medical Monitor.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules
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2 capsules, once a day for two weeks
1 capsule once a day for 4 weeks (MBX-8025 50 mg capsule) 1 capsule once a day for 4 weeks (MBX-8025 50 mg or 100 mg capsule) 1 or 2 capsules once a day for 4 weeks (MBX-8025 50 mg, 100 mg or two (2) 100 mg capsules) |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
LDL-C
Time Frame: 12-Weeks
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Absolute and percentage (%) reduction in serum LDL-C at any point from baseline through Week 16.
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12-Weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total Cholesterol (TC)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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High-density lipoprotein (HDL) cholesterol [HDL-C]
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Very Low-Density Lipoprotein (VLDL)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Non HDL-C
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Remnant-like Particle (RLP-C)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Apolipoprotein B (Apo B)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Apolipoprotein A-I (Apo A-I)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Lipoprotein
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Serum Triglyceride (TG)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Apolipoprotein C-III (Apo CIII)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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C reactive protein hs-(CRP)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16
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12-Weeks
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MBX-8025 Plasma Concentration Levels
Time Frame: 12-Weeks
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Blood samples for the plasma concentration determination of MBX-8025 and its metabolites (M1, M2 and M3) collected pre-dose at the following visits: 4, 5, 6, 7, 8 and 9.
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12-Weeks
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Safety Measures: Number of Participants with Adverse Events as a Measure of Safety
Time Frame: 12-Weeks
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Complete characterization of Adverse Events (AE), Biochemistry and Hematology
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12-Weeks
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Proprotein convertase subtilisin/kexin type 9 (PCSK-9)
Time Frame: 12-Weeks
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Absolute and percentage change at any point from baseline through Week 16 for the following: Proprotein convertase subtilisin/kexin type 9 (PCSK-9)
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12-Weeks
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Pol F Boudes, M.D., CymaBay Therapeutics, Inc.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CB8025-21427
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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