A 12-week, open-label , all subjects will first receive 2 weeks of placebo drug and then active medication in a dose escalating manner: each patient will first receive 50 mg, after evaluation the option exists to increase the dose to to 100 mg and after another evaluation to 200 mg active study drug, phase 2 study to evaluate the effects of MBX-8025 in patients with Homozygous Familial Hypercholesterolemia (HoFH)

• Register: EUCTR
• Last refreshed on: 3 October 2016
• Main ID: EUCTR2014-004856-68-NO
• Date of registration: 26/01/2015
• Prospective Registration: Yes
• Primary sponsor: CymaBay Therapeutics, Inc.
• Public title: A 12-week, open-label , all subjects will first receive 2 weeks of placebo drug and then active medication in a dose escalating manner: each patient will first receive 50 mg, after evaluation the option exists to increase the dose to to 100 mg and after another evaluation to 200 mg active study drug, phase 2 study to evaluate the effects of MBX-8025 in patients with Homozygous Familial Hypercholesterolemia (HoFH)
• Scientific 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)
• Date of first enrolment: 29/04/2015
• Target sample size: 8
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004856-68
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Netherlands, Norway

Contacts

• Name: Pol Boudes
• Affiliation: CymaBay Therapeutics, Inc.

• Name: Pol Boudes
• Affiliation: CymaBay Therapeutics, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusions:
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 mutants alleles at the LDL-Receptor gene locus).
3. 18 years of age or older.
4. Existing lipid lowering therapies (statins, cholesterol absorption inhibitors, bile acid sequestrants, nicotinic acid and their combinations, 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 AHA.
6. Fasting LDL-C = 4.8 mmol/L (= 185.6 mg/dL) during screening.
7. For females 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. For male subjects, use of appropriate contraception (e.g., condoms) so their female partners of reproductive potential do not become pregnant during the study and for at least two weeks after the last dose.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
Exclusions:
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 prior to Screening Visit.
5. Planned cardiac surgery, or planned revascularization, in the next four months.
6. Uncontrolled hypertension.
7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 3 times the upper limit of normal (ULN).
8. Unexplained creatine kinase (CK) = 5 times the 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Homozygous Familial Hypercholesterolemia

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: MBX-8025
Product Code: MBX-8025
Pharmaceutical Form: Capsule
INN or Proposed INN: MBX-8025
CAS Number: 928821-40-3
Current Sponsor code: MBX-8025
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 50-100
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To evaluate the effects of MBX-8025 on other lipid parameters
To evaluate the safety and tolerability of MBX-8025 in patients with HoFH.
To evaluate steady-state trough plasma levels of MBX-8025 and its metabolites, M1, M2 and M3
Exploratory:
To evaluate the effects of MBX-8025 on proprotein convertase subtilisin/kexin type 9 (PCSK9) and high sensitivity C reactive protein (hs-CRP).

Main Objective: Primary:
To evaluate the effect of MBX-8025 on Low Density Lipoprotein Cholesterol (LDL-C).

Primary end point(s): The effect of MBX-8025 on Serum LDL-C.

Timepoint(s) of evaluation of this end point: All visits after first drug administration: visit 4-10

Secondary Outcome(s)

Secondary end point(s): The effect of MBX-8025 on other lipid parameters, safety and tolerability and PK of MBX-8025 and it's metabolites.

Timepoint(s) of evaluation of this end point: All visits after first drug administration: visit 4-10

Secondary ID(s)

CB8025-21427

Source(s) of Monetary Support

CymaBay Therapeutics, Inc