Phase 3 Study Overview

Juxtapid was studied in a phase 3 clinical trial involving 29 patients aged 18 and older with HoFH.

Objective
Evaluate the safety and effectiveness of Juxtapid as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available.

Design
Phase 3 multinational, single-arm, open-label study of Juxtapid.

Methods
A diagnosis of HoFH was defined by the presence of at least one of the following clinical criteria: (1) documented functional mutation(s) in both LDL receptor alleles or alleles known to affect LDL receptor functionality, or (2) skin fibroblast LDL receptor activity <20% normal, or (3) untreated TC >500 mg/dL and TG <300 mg/dL and both parents with documented untreated TC >250 mg/dL.

78 Week Study with 3 Time Periods:


During the Minimum 6-week Run-in period:

  • Background lipid-lowering therapies (LLTs) including apheresis were stabilized.
  • Patients were instructed to initiate and maintain a low-fat diet supplying <20% energy from fat.
  • Patients were instructed to take dietary supplements that provided approximately 400 IU vitamin E, 210 mg ALA, 200 mg linoleic acid, 110 mg EPA, and 80 mg DHA per day.

From Week 0 to Week 26 (Efficacy Phase):

  • Juxtapid was initiated at 5 mg daily and titrated to daily doses of 10 mg, 20 mg, 40 mg, and 60 mg at Weeks 2, 6, 10, and 14, respectively, based on tolerability and acceptable levels of transaminases.
  • Patients were instructed to maintain a low-fat diet and take daily vitamin E and essential fatty acids at levels described above throughout the study.
  • Dose of concomitant LLTs were to remain unchanged.

From Week 26 to Week 78 (Safety Phase):

  • Patients continued on maximum tolerated dose of Juxtapid established during the efficacy phase.
  • Changes in concomitant LLTs were allowed unless dose alteration rules were met.
  • An extension study was available for patients who successfully completed the phase 3 study

Key Efficacy End Points

  • Percent reduction in LDL-C at Week 26
  • Percent reduction in LDL-C in patients completing the efficacy period (26 weeks) 
  • Percent change from baseline in other lipids and lipoproteins

Study Population
At the start of the study, all patients were receiving lipid-lowering therapies. As shown in the table below, 27 (93%) were receiving statins, 76% were receiving ezetimibe, 10% were receiving nicotinic acid, 3% each were receiving a bile acid sequestrant and fibrate, and 18 (62%) were receiving apheresis.

The baseline demographics and characteristics of the enrolled patients are illustrated in the tables below.

Baseline Demographics and Characteristics

Characteristics of patients with HoFH (homozygous FH) in the Juxtapid phase 3 trial
 

Baseline LDL-C Levels
Subjects in the study exhibited a wide range of baseline LDL-C levels, ranging from 152 mg/dL to 564 mg/dL, as shown in the figure below.

LDL-C levels of HoFH patients in the Juxtapid phase 3 trial

Learn more about the results of this study here.