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

Homozygous Familial Hypercholesterolemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02472535
• Other study ID #: CB8025-21427
• Status: Completed
• Phase: Phase 2
• First received: May 22, 2015
• Last updated: March 8, 2016
• Start date: April 2015
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: CymaBay Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Homozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Other:
• Run-In Period: Placebo
2 capsules, once a day for two weeks

Drug:
• MBX-8025 50 mg (Dose Escalation Period 1)
1 capsule once a day for 4 weeks (MBX-8025 50 mg capsule)
• MBX-8025 50 mg or 100 mg (Dose Escalation Period 2)
1 capsule once a day for 4 weeks (MBX-8025 50 mg or 100 mg capsule)
• MBX-8025 50 mg, 100 mg or 200 mg (Dose Escalation Period 3)
1 or 2 capsules once a day for 4 weeks (MBX-8025 50 mg, 100 mg or two (2) 100 mg capsules)

Locations

Country	Name	City	State
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
France	Endocrinologie metabolisme et prevention cardiovasulaire, Institut E3M et IHU cardiometabolique (ICAN), Hôpital Pitié Salpêtrière	Paris
Netherlands	Radbound UMC	Nijmegen
Norway	Lipidklinikken, Oslo Universitetssykehus	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
CymaBay Therapeutics, Inc.

Countries where clinical trial is conducted

Canada,  France,  Netherlands,  Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	C reactive protein hs-(CRP)	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Other	MBX-8025 Plasma Concentration Levels	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	No
Other	Safety Measures: Number of Participants with Adverse Events as a Measure of Safety	Complete characterization of Adverse Events (AE), Biochemistry and Hematology	12-Weeks	Yes
Other	Proprotein convertase subtilisin/kexin type 9 (PCSK-9)	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	No
Primary	LDL-C	Absolute and percentage (%) reduction in serum LDL-C at any point from baseline through Week 16.	12-Weeks	No
Secondary	Total Cholesterol (TC)	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	High-density lipoprotein (HDL) cholesterol [HDL-C]	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	Very Low-Density Lipoprotein (VLDL)	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	Non HDL-C	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	Remnant-like Particle (RLP-C)	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	Apolipoprotein B (Apo B)	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	Apolipoprotein A-I (Apo A-I)	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	Lipoprotein	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	Serum Triglyceride (TG)	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No
Secondary	Apolipoprotein C-III (Apo CIII)	Absolute and percentage change at any point from baseline through Week 16	12-Weeks	No