A Phase 2 Open-Label, Dose-Finding Study to Assess the Efficacy, Safety, and Tolerability of Gemcabene in Patients With Homozygous Familial Hypercholesterolemia on Stable, Lipid Lowering Therapy (COBALT-1)

NeuroBo Pharmaceuticals Inc.7 sites in 3 countries8 target enrollmentJune 2016

ConditionsHypercholesteremia

InterventionsGemcabene

DrugsGemcabene

Overview

Phase: Phase 2
Intervention: Gemcabene
Conditions: Hypercholesteremia
Sponsor: NeuroBo Pharmaceuticals Inc.
Enrollment: 8
Locations: 7
Primary Endpoint: Percent Change From Baseline in LDL-C at Day 28
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study was to assess the efficacy, safety, and tolerability of multiple doses of Gemcabene in patients with HoFH on stable, lipid-lowering therapy.

Registry

clinicaltrials.gov

Start Date

June 2016

End Date

July 2017

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

NeuroBo Pharmaceuticals Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provision of written and signed informed consent (by patient or legal guardian) prior to any study-specific procedure;
•Male or female ≥17 years of age at time of consent;
•Diagnosis of HoFH by genetic confirmation (including compound heterozygosity) or a clinical diagnosis based on either (1) a history of an untreated LDL-C concentration \>500 mg/dL (12.92 mmol/L) together with either appearance of xanthoma before 10 years of age, or evidence of heterozygous familial hypercholesterolemia in both parents or, if history is unavailable, (2) LDL-C \>300 mg/dL (7.76 mmol/L) on maximally tolerated lipid-lowering drug therapy;
•Currently on a stable, low-fat, low-cholesterol diet in combination with a pre-existing, regulatory-approved, not excluded lipid-lowering therapy (i.e., statins, monoclonal antibodies to PCSK9, cholesterol absorption inhibitors, bile acid sequestrants, or nicotinic acid, or any combination thereof) at a stable dose for at least 4 weeks prior to the Screening Visit;
•Fasting LDL-C value \>130 mg/dL (3.36 mmol/L) at the Screening Visit;
•Physical examination, including vital signs, that is within normal limits or clinically acceptable to the Investigator;
•Weight ≥50 kg;
•Female patients must not be pregnant or lactating. Women of child-bearing potential must have a negative serum pregnancy test at the Screening Visit and negative urine dipstick on Day 1 prior to dosing in order to qualify for the study. Women who are surgically sterile or are clinically confirmed to be post-menopausal (i.e., documented amenorrhea for ≥1 year in the absence of other biological or physiological causes) are not considered to be of child-bearing potential; and
•Women of child-bearing potential must agree to use acceptable methods of contraception throughout the duration of the study and for 30 days after the last dose of study drug. For this study, double-barrier contraception is required.

Exclusion Criteria

•Other forms of primary hyperlipoproteinemia and secondary causes of hypercholesterolemia (e.g., nephrotic syndrome or hypothyroidism);
•Abnormal liver function test at the Screening Visit (aspartate aminotransferase or alanine aminotransferase \>2 × the upper limit of normal \[ULN\]; total bilirubin \>1.5 × ULN; or alkaline phosphatase \>2 × ULN based on appropriate age and gender normal values). Patients with bilirubin \>1.5 × ULN and history of Gilbert's syndrome may be included; reflexive direct bilirubin testing will be used to confirm Gilbert's syndrome;
•Moderate (Grade B) or severe (Grade C) chronic hepatic impairment according to the Child Pugh classification;
•Active liver disease (e.g., cirrhosis, alcoholic liver disease, hepatitis B virus \[HBV\], hepatitis C virus \[HCV\], autoimmune hepatitis, liver failure, liver cancer), history of liver transplant, or known diagnosis of human immunodeficiency virus (HIV);
•Triglycerides value \>400 mg/dL (4.52 mmol/L) at the Screening Visit;
•Moderate to severe renal insufficiency defined as an estimated GFR \<30 mL/min/1.73m2 (calculated using The Chronic Kidney Disease Epidemiology Collaboration equation) at the Screening Visit;
•Abnormal urinalysis (proteinuria greater than trace or any male or non-menstruating female with greater than trace hematuria), confirmed by reflexive urine protein:creatinine ratio testing;
•Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) below the lower limit of normal or \>1.5 × ULN, respectively, at the Screening Visit. If controlled, treatment should be stable for at least 3 months prior to the Screening Visit;
•Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (hemoglobin A1c \[HbA1c\] value \>8%), or any diabetic patient taking insulin and/or thiazolidinediones;
•New York Heart Association Class III or IV heart failure;

Arms & Interventions

Gemcabene

Participants with homozygous familial hypercholesterolemia (HoFH) on stable lipid lowering therapy received 300 milligram (mg) of Gemcabene, orally once daily from day 1 to 28 followed by 600 mg of Gemcabene, orally once daily from day 29 to 56 followed by 900 mg of Gemcabene, orally once daily from day 57 to 84. Participants were followed until Day 112.

Intervention: Gemcabene

Outcomes

Primary Outcomes

Percent Change From Baseline in LDL-C at Day 28

Time Frame: Baseline, day 28

Percent Change From Baseline in LDL-C at Day 56

Time Frame: Baseline, day 56

Percent Change From Baseline in LDL-C at Day 84

Time Frame: Baseline, day 84

Secondary Outcomes

Change From Baseline in Fibrinogen(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting LDL-C(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Non-HDL-C(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting VLDL-C(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting HDL-C(Baseline, days 28, 56 and 84)
Number of Participants Achieving LDL-C Reduction of ≥25%(Days 28, 56 and 84)
Percent Change From Baseline in Fasting Non-HDL-C(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Total Cholesterol (TC)(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Total Cholesterol (TC)(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Triglycerides (TG)(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Triglycerides (TG)(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting HDL-C(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting VLDL-C(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting VLDL-C as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting LDL-C as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting HDL-C as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting VLDL-C as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting LDL-C as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Non-HDL-C as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Non-HDL-C as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting HDL-C as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting TC as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting TC as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting TG as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting TG as Per Receptor Mutation Status(Baseline, days 28, 56 and 84)
Number of Participants Achieving LDL-C Reduction of ≥15%(Days 28, 56 and 84)
Number of Participants Achieving LDL-C Reduction of ≥20%(Days 28, 56 and 84)
Number of Participants Achieving LDL-C Reduction of ≥30%(Days 28, 56 and 84)
Percent Change From Baseline in Fibrinogen(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Lipoprotein(a)(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Apolipoprotein A-I(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Apolipoprotein A-I(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Apolipoprotein A-II(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Apolipoprotein E(Baseline, days 28, 56 and 84)
Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L)(Days 28, 56 and 84)
Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)(Baseline, days 28, 56 and 84)
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Apolipoprotein B(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Apolipoprotein B(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Apolipoprotein E(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Lipoprotein(a)(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Apolipoprotein C-II(Baseline, days 28, 56 and 84)
Percent Change From Baseline in Fasting Apolipoprotein C-III(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Apolipoprotein A-II(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Apolipoprotein C-II(Baseline, days 28, 56 and 84)
Change From Baseline in Fasting Apolipoprotein C-III(Baseline, days 28, 56 and 84)