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

March 8, 2016 updated by: CymaBay Therapeutics, Inc.

A 12-week, Open-label, Dose-escalating, Phase 2 Study to Evaluate the Effects of MBX-8025 in Patients With Homozygous Familial Hypercholesterolemia (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

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

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 7K9
        • Ecogene-21
      • Montreal, Quebec, Canada, H1T 1C8
        • Montreal Heart Institute
      • Paris, France, 75 013
        • Endocrinologie metabolisme et prevention cardiovasulaire, Institut E3M et IHU cardiometabolique (ICAN), Hôpital Pitié Salpêtrière
      • Nijmegen, Netherlands, 6525 GA
        • Radbound UMC
      • Oslo, Norway, N-0373
        • Lipidklinikken, Oslo Universitetssykehus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Experimental: placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules
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
Absolute and percentage (%) reduction in serum LDL-C at any point from baseline through Week 16.
12-Weeks

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
C reactive protein hs-(CRP)
Time Frame: 12-Weeks
Absolute and percentage change at any point from baseline through Week 16
12-Weeks
MBX-8025 Plasma Concentration Levels
Time Frame: 12-Weeks
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.
12-Weeks
Safety Measures: Number of Participants with Adverse Events as a Measure of Safety
Time Frame: 12-Weeks
Complete characterization of Adverse Events (AE), Biochemistry and Hematology
12-Weeks
Proprotein convertase subtilisin/kexin type 9 (PCSK-9)
Time Frame: 12-Weeks
Absolute and percentage change at any point from baseline through Week 16 for the following: Proprotein convertase subtilisin/kexin type 9 (PCSK-9)
12-Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Pol F Boudes, M.D., CymaBay Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Actual)

February 1, 2016

Study Completion (Actual)

February 1, 2016

Study Registration Dates

First Submitted

May 22, 2015

First Submitted That Met QC Criteria

June 11, 2015

First Posted (Estimate)

June 16, 2015

Study Record Updates

Last Update Posted (Estimate)

March 9, 2016

Last Update Submitted That Met QC Criteria

March 8, 2016

Last Verified

March 1, 2016

More Information

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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