Study to Evaluate the Effects of MBX-8025 in Patients With HoFH

Phase 2

Completed

• Conditions: Homozygous Familial Hypercholesterolemia
• Interventions: Drug: MBX-8025 50 mg (Dose Escalation Period 1); Drug: MBX-8025 50 mg or 100 mg (Dose Escalation Period 2); Drug: MBX-8025 50 mg, 100 mg or 200 mg (Dose Escalation Period 3)

• Registration Number: NCT02472535
• Lead Sponsor: CymaBay Therapeutics, Inc.

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.

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-05-22
• Study First Submitted QC: 2015-06-11
• Study First Posted: 2015-06-16
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-08
• Last Update Posted: 2016-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. 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.
2. 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).
3. 18 years of age or older.
4. 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.
5. Stable lipid lowering diet compatible with a Step I diet of the American Heart Association (AHA).
6. Fasting LDL-C ≥ 4.8 mmol/L (≥ 185.6 mg/dL) during screening.
7. 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

1. Treatment with lomitapide or mipomersen within two months of screening.
2. 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%.
3. Uncontrolled cardiac arrhythmia during the past three months of screening.
4. Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke during the past three months of screening.
5. Planned cardiac surgery, or planned revascularization, in the next four months.
6. Uncontrolled hypertension.
7. Aspartate transaminase (AST) or Alanine transaminase (ALT) ≥ 3 times the Upper Limit of Normal (ULN).
8. Unexplained creatine kinase (CK) ≥ 5 times the upper limit of normal (ULN).
9. For females, pregnancy or breast-feeding.
10. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules	MBX-8025 50 mg (Dose Escalation Period 1)	-
placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules	MBX-8025 50 mg or 100 mg (Dose Escalation Period 2)	-
placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules	MBX-8025 50 mg, 100 mg or 200 mg (Dose Escalation Period 3)	-

Primary Outcome Measures

Name	Time	Method
LDL-C	12-Weeks	Absolute and percentage (%) reduction in serum LDL-C at any point from baseline through Week 16.

Secondary Outcome Measures

Name	Time	Method
Total Cholesterol (TC)	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
High-density lipoprotein (HDL) cholesterol [HDL-C]	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
Remnant-like Particle (RLP-C)	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
Apolipoprotein B (Apo B)	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
Lipoprotein	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
Very Low-Density Lipoprotein (VLDL)	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
Non HDL-C	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
Apolipoprotein C-III (Apo CIII)	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
Apolipoprotein A-I (Apo A-I)	12-Weeks	Absolute and percentage change at any point from baseline through Week 16
Serum Triglyceride (TG)	12-Weeks	Absolute and percentage change at any point from baseline through Week 16

Trial Locations

Locations (5)

Ecogene-21; 🇨🇦 Chicoutimi, Quebec, Canada

Montreal Heart Institute; 🇨🇦 Montreal, Quebec, Canada

Endocrinologie metabolisme et prevention cardiovasulaire, Institut E3M et IHU cardiometabolique (ICAN), Hôpital Pitié Salpêtrière; 🇫🇷 Paris, France

Lipidklinikken, Oslo Universitetssykehus; 🇳🇴 Oslo, Norway

Radbound UMC; 🇳🇱 Nijmegen, Netherlands