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Efficacy and Safety of Gemcabene in Patients With Homozygous Familial Hypercholesterolemia on Stable, Lipid-Lowering Therapy (COBALT-1)

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ClinicalTrials.gov Identifier: NCT02722408
Recruitment Status : Completed
First Posted : March 30, 2016
Results First Posted : June 25, 2020
Last Update Posted : June 25, 2020
Sponsor:
Information provided by (Responsible Party):
NeuroBo Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE March 12, 2016
First Posted Date  ICMJE March 30, 2016
Results First Submitted Date  ICMJE June 3, 2020
Results First Posted Date  ICMJE June 25, 2020
Last Update Posted Date June 25, 2020
Actual Study Start Date  ICMJE June 2016
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2020)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 23, 2016)
LDL-C [ Time Frame: Baseline and 28, 56, and 84 days ]
Percent change from baseline
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2020)
  • Change From Baseline in Fasting LDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Non-HDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Non-HDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Total Cholesterol (TC) [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Total Cholesterol (TC) [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Triglycerides (TG) [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Triglycerides (TG) [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting HDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting HDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting VLDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting VLDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting LDL-C as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Change From Baseline in Fasting LDL-C as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Percent Change From Baseline in Fasting Non-HDL-C as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Change From Baseline in Fasting Non-HDL-C as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Percent Change From Baseline in Fasting VLDL-C as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Change From Baseline in Fasting VLDL-C as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Percent Change From Baseline in Fasting HDL-C as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Change From Baseline in Fasting HDL-C as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Percent Change From Baseline in Fasting TC as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Change From Baseline in Fasting TC as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Percent Change From Baseline in Fasting TG as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Change From Baseline in Fasting TG as Per Receptor Mutation Status [ Time Frame: Baseline, days 28, 56 and 84 ]
    Receptor mutation status was categorized as LDLr status and EAS clinical diagnosis of HoFH which was reported in this outcome measure.
  • Number of Participants Achieving LDL-C Reduction of ≥15% [ Time Frame: Days 28, 56 and 84 ]
  • Number of Participants Achieving LDL-C Reduction of ≥20% [ Time Frame: Days 28, 56 and 84 ]
  • Number of Participants Achieving LDL-C Reduction of ≥25% [ Time Frame: Days 28, 56 and 84 ]
  • Number of Participants Achieving LDL-C Reduction of ≥30% [ Time Frame: Days 28, 56 and 84 ]
  • Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) [ Time Frame: Days 28, 56 and 84 ]
  • Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fibrinogen [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fibrinogen [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Lipoprotein(a) [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Lipoprotein(a) [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Apolipoprotein B [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Apolipoprotein B [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Apolipoprotein A-I [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Apolipoprotein A-I [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Apolipoprotein A-II [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Apolipoprotein A-II [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Apolipoprotein C-II [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Apolipoprotein C-II [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Apolipoprotein C-III [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Apolipoprotein C-III [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Percent Change From Baseline in Fasting Apolipoprotein E [ Time Frame: Baseline, days 28, 56 and 84 ]
  • Change From Baseline in Fasting Apolipoprotein E [ Time Frame: Baseline, days 28, 56 and 84 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2016)
  • non-HDL-C [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Total Cholesterol [TC] [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Triglycerides [TG] [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • HDL-C [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Very low-density lipoprotein [VLDL-C] [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • hsCRP [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Fibrinogen [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Lipoprotein(a) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Apolipoprotein B (ApoB) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Apolipoprotein A-1 (ApoA-1) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Apolipoprotein A-II (ApoA-II) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Apolipoprotein C-II (ApoC-II) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Apolipoprotein C-III (ApoC-III) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Apolipoprotein E(ApoE) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline
  • Adverse Events [ Time Frame: 84 days ]
  • Clinical Laboratory [ Time Frame: 84 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Gemcabene in Patients With Homozygous Familial Hypercholesterolemia on Stable, Lipid-Lowering Therapy (COBALT-1)
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hypercholesteremia
Intervention  ICMJE Drug: Gemcabene
300 mg tablet orally once daily for four weeks followed by 600 mg tablet orally once daily for four weeks followed by 900 mg tablet orally once daily for four weeks.
Study Arms  ICMJE Experimental: 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: Drug: Gemcabene
Publications * Gaudet D, Durst R, Lepor N, Bakker-Arkema R, Bisgaier C, Masson L, Golden L, Kastelein JJ, Hegele RA, Stein E. Usefulness of Gemcabene in Homozygous Familial Hypercholesterolemia (from COBALT-1). Am J Cardiol. 2019 Dec 15;124(12):1876-1880. doi: 10.1016/j.amjcard.2019.09.010. Epub 2019 Sep 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 23, 2016)
8
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2017
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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;
  • Myocardial infarction, severe or unstable angina pectoris, coronary angioplasty, coronary artery bypass graft, or other major cardiovascular events resulting in hospitalization within 3 months of the Screening Visit. Patients with adequately treated stable angina, per Investigator assessment, may be included;
  • Uncontrolled cardiac arrhythmia or prolonged QT on the Screening Visit or Day 1 prior to dosing ECG (QTcF >450 msec for men and >470 msec for women) or known family history of prolonged QT or unexplained sudden cardiac death;
  • Uncontrolled hypertension, defined as sitting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg, and confirmed by repeat measurement;
  • Currently receiving cancer treatments or, in the Investigator's opinion, at risk of relapse for recent cancer;
  • Use of fibrate lipid-lowering agent 6 weeks prior to the Screening Visit;
  • Hypersensitivity to or a history of significant adverse reactions to any fibrate lipid lowering agent;
  • Use of apheresis (LDL or plasma) 8 weeks prior to the Screening Visit;
  • Use of lomitapide 2 months prior to the Screening Visit;
  • Use of mipomersen 5 months prior to the Screening Visit;
  • Use of any excluded medications or supplements (e.g., potent cytochrome P450 [CYP] 3A4 inhibitors);
  • History of drug or alcohol abuse within the past year or inability to comply with protocol requirements, including subject restrictions;
  • Previously treated with gemcabene;
  • Participation in another clinical study of an investigational agent or device concurrently or within 1 month prior to the Screening Visit, or use of an investigational agent within 1 month or 5 half-lives (if known), whichever is longer, prior to the Screening Visit; or
  • Any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 17 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Israel,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02722408
Other Study ID Numbers  ICMJE GEM-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NeuroBo Pharmaceuticals Inc.
Study Sponsor  ICMJE NeuroBo Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account NeuroBo Pharmaceuticals Inc.
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP