Clinical trial NCT02472535: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Homozygous Familial Hypercholesterolemia
Keywords: HoFH
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-06-16
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: LDL-C
timeFrame: 12-Weeks
Secondary outcomes:
measure: Total Cholesterol (TC)
timeFrame: 12-Weeks
measure: High-density lipoprotein (HDL) cholesterol [HDL-C]
timeFrame: 12-Weeks
measure: Very Low-Density Lipoprotein (VLDL)
timeFrame: 12-Weeks
measure: Non HDL-C
timeFrame: 12-Weeks
measure: Remnant-like Particle (RLP-C)
timeFrame: 12-Weeks
measure: Apolipoprotein B (Apo B)
timeFrame: 12-Weeks
measure: Apolipoprotein A-I (Apo A-I)
timeFrame: 12-Weeks
measure: Lipoprotein
timeFrame: 12-Weeks
measure: Serum Triglyceride (TG)
timeFrame: 12-Weeks
measure: Apolipoprotein C-III (Apo CIII)
timeFrame: 12-Weeks
Other outcomes:
measure: C reactive protein hs-(CRP)
timeFrame: 12-Weeks
measure: MBX-8025 Plasma Concentration Levels
timeFrame: 12-Weeks
measure: Safety Measures: Number of Participants with Adverse Events as a Measure of Safety
timeFrame: 12-Weeks
measure: Proprotein convertase subtilisin/kexin type 9 (PCSK-9)
timeFrame: 12-Weeks
Locations:
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Paris
country: France
facility: Endocrinologie metabolisme et prevention cardiovasulaire, Institut E3M et IHU cardiometabolique (ICAN), Hôpital Pitié Salpêtrière
city: Nijmegen
country: Netherlands
facility: Radbound UMC
city: Oslo
country: Norway
facility: Lipidklinikken, Oslo Universitetssykehus
Study officials:
affiliation: Gilead Sciences
name: Pol F Boudes, M.D.
role: STUDY_CHAIR
References: