Back to resultsStudy to Evaluate the Effects of MBX-8025 in Patients With HoFH
Primary Purpose
Homozygous Familial Hypercholesterolemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Run-In Period: Placebo
MBX-8025 50 mg (Dose Escalation Period 1)
MBX-8025 50 mg or 100 mg (Dose Escalation Period 2)
MBX-8025 50 mg, 100 mg or 200 mg (Dose Escalation Period 3)
Sponsored by
About this trial
This is an interventional treatment trial for Homozygous Familial Hypercholesterolemia focused on measuring HoFH
Eligibility Criteria
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.
Sites / Locations
- Ecogene-21
- Montreal Heart Institute
- Endocrinologie metabolisme et prevention cardiovasulaire, Institut E3M et IHU cardiometabolique (ICAN), Hôpital Pitié Salpêtrière
- Radbound UMC
- Lipidklinikken, Oslo Universitetssykehus
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules
Arm Description
Outcomes
Primary Outcome Measures
LDL-C
Absolute and percentage (%) reduction in serum LDL-C at any point from baseline through Week 16.
Secondary Outcome Measures
Total Cholesterol (TC)
Absolute and percentage change at any point from baseline through Week 16
High-density lipoprotein (HDL) cholesterol [HDL-C]
Absolute and percentage change at any point from baseline through Week 16
Very Low-Density Lipoprotein (VLDL)
Absolute and percentage change at any point from baseline through Week 16
Non HDL-C
Absolute and percentage change at any point from baseline through Week 16
Remnant-like Particle (RLP-C)
Absolute and percentage change at any point from baseline through Week 16
Apolipoprotein B (Apo B)
Absolute and percentage change at any point from baseline through Week 16
Apolipoprotein A-I (Apo A-I)
Absolute and percentage change at any point from baseline through Week 16
Lipoprotein
Absolute and percentage change at any point from baseline through Week 16
Serum Triglyceride (TG)
Absolute and percentage change at any point from baseline through Week 16
Apolipoprotein C-III (Apo CIII)
Absolute and percentage change at any point from baseline through Week 16
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02472535
Brief Title
Study to Evaluate the Effects of MBX-8025 in Patients With HoFH
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CymaBay Therapeutics, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A 12-week, open-label, dose-escalating, phase 2 study to evaluate the effects of MBX-8025 in patients with Homozygous Familial Hypercholesterolemia (HoFH).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Homozygous Familial Hypercholesterolemia
Keywords
HoFH
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
Run-In Period: Placebo
Intervention Description
2 capsules, once a day for two weeks
Intervention Type
Drug
Intervention Name(s)
MBX-8025 50 mg (Dose Escalation Period 1)
Intervention Description
1 capsule once a day for 4 weeks
(MBX-8025 50 mg capsule)
Intervention Type
Drug
Intervention Name(s)
MBX-8025 50 mg or 100 mg (Dose Escalation Period 2)
Intervention Description
1 capsule once a day for 4 weeks
(MBX-8025 50 mg or 100 mg capsule)
Intervention Type
Drug
Intervention Name(s)
MBX-8025 50 mg, 100 mg or 200 mg (Dose Escalation Period 3)
Intervention Description
1 or 2 capsules once a day for 4 weeks
(MBX-8025 50 mg, 100 mg or two (2) 100 mg capsules)
Primary Outcome Measure Information:
Title
LDL-C
Description
Absolute and percentage (%) reduction in serum LDL-C at any point from baseline through Week 16.
Time Frame
12-Weeks
Secondary Outcome Measure Information:
Title
Total Cholesterol (TC)
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
High-density lipoprotein (HDL) cholesterol [HDL-C]
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
Very Low-Density Lipoprotein (VLDL)
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
Non HDL-C
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
Remnant-like Particle (RLP-C)
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
Apolipoprotein B (Apo B)
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
Apolipoprotein A-I (Apo A-I)
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
Lipoprotein
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
Serum Triglyceride (TG)
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
Apolipoprotein C-III (Apo CIII)
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Other Pre-specified Outcome Measures:
Title
C reactive protein hs-(CRP)
Description
Absolute and percentage change at any point from baseline through Week 16
Time Frame
12-Weeks
Title
MBX-8025 Plasma Concentration Levels
Description
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.
Time Frame
12-Weeks
Title
Safety Measures: Number of Participants with Adverse Events as a Measure of Safety
Description
Complete characterization of Adverse Events (AE), Biochemistry and Hematology
Time Frame
12-Weeks
Title
Proprotein convertase subtilisin/kexin type 9 (PCSK-9)
Description
Absolute and percentage change at any point from baseline through Week 16 for the following: Proprotein convertase subtilisin/kexin type 9 (PCSK-9)
Time Frame
12-Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pol F Boudes, M.D.
Organizational Affiliation
CymaBay Therapeutics, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Ecogene-21
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
Montreal Heart Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 1C8
Country
Canada
Facility Name
Endocrinologie metabolisme et prevention cardiovasulaire, Institut E3M et IHU cardiometabolique (ICAN), Hôpital Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75 013
Country
France
Facility Name
Radbound UMC
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Lipidklinikken, Oslo Universitetssykehus
City
Oslo
ZIP/Postal Code
N-0373
Country
Norway
12. IPD Sharing Statement
Learn more about this trial
Study to Evaluate the Effects of MBX-8025 in Patients With HoFH
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