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

NCT02472535 | Completed Phase 2 DMC

• 1 other identifier: CB8025-21427
• Study Type: interventional
• Target: 13
• Locations: 4 countries
• Sites: 5

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).

Conditions

Homozygous Familial Hypercholesterolemia

Keywords

HoFH

Outcome Measures

Primary Outcomes (1)

• LDL-C

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

  12-Weeks

Secondary Outcomes (10)

• Total Cholesterol (TC)

  12-Weeks

• High-density lipoprotein (HDL) cholesterol [HDL-C]

  12-Weeks

• Very Low-Density Lipoprotein (VLDL)

  12-Weeks

• Non HDL-C

  12-Weeks

• Remnant-like Particle (RLP-C)

  12-Weeks

Other Outcomes (4)

• C reactive protein hs-(CRP)

  12-Weeks

• MBX-8025 Plasma Concentration Levels

  12-Weeks

• Safety Measures: Number of Participants with Adverse Events as a Measure of Safety

  12-Weeks

Study Arms (1)

placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules

EXPERIMENTAL

Other: Run-In Period: Placebo; 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)

Interventions

Run-In Period: Placebo OTHER

2 capsules, once a day for two weeks

placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules

MBX-8025 50 mg (Dose Escalation Period 1) DRUG

1 capsule once a day for 4 weeks (MBX-8025 50 mg capsule)

placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules

MBX-8025 50 mg or 100 mg (Dose Escalation Period 2) DRUG

1 capsule once a day for 4 weeks (MBX-8025 50 mg or 100 mg capsule)

placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules

MBX-8025 50 mg, 100 mg or 200 mg (Dose Escalation Period 3) DRUG

1 or 2 capsules once a day for 4 weeks (MBX-8025 50 mg, 100 mg or two (2) 100 mg capsules)

placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (5)

Ecogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Endocrinologie metabolisme et prevention cardiovasulaire, Institut E3M et IHU cardiometabolique (ICAN), Hôpital Pitié Salpêtrière

Paris, 75 013, France

Location

Radbound UMC

Nijmegen, 6525 GA, Netherlands

Location

Lipidklinikken, Oslo Universitetssykehus

Oslo, N-0373, Norway

Location

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

(2-methyl-4-(5-methyl-2-(4-trifluoromethyl-phenyl)-2H-(1,2,3)triazol-4-ylmethylsulfanyl)phenoxy)acetic acid

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Pol F Boudes, M.D.

  Gilead Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2015
• First Posted: June 16, 2015
• Study Start: April 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: March 9, 2016

Record last verified: 2016-03

Locations

NL (1); CA (2); NO (1); FR (1)