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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.

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.

Condition or disease Intervention/treatment Phase
Hypercholesteremia Drug: Gemcabene Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : June 2016
Actual Primary Completion Date : April 2017
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.




Primary Outcome Measures :
  1. Percent Change From Baseline in LDL-C at Day 28 [ Time Frame: Baseline, day 28 ]
  2. Percent Change From Baseline in LDL-C at Day 56 [ Time Frame: Baseline, day 56 ]
  3. Percent Change From Baseline in LDL-C at Day 84 [ Time Frame: Baseline, day 84 ]

Secondary Outcome Measures :
  1. Change From Baseline in Fasting LDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  2. Percent Change From Baseline in Fasting Non-HDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  3. Change From Baseline in Fasting Non-HDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  4. Percent Change From Baseline in Fasting Total Cholesterol (TC) [ Time Frame: Baseline, days 28, 56 and 84 ]
  5. Change From Baseline in Fasting Total Cholesterol (TC) [ Time Frame: Baseline, days 28, 56 and 84 ]
  6. Percent Change From Baseline in Fasting Triglycerides (TG) [ Time Frame: Baseline, days 28, 56 and 84 ]
  7. Change From Baseline in Fasting Triglycerides (TG) [ Time Frame: Baseline, days 28, 56 and 84 ]
  8. Percent Change From Baseline in Fasting HDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  9. Change From Baseline in Fasting HDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  10. Percent Change From Baseline in Fasting VLDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  11. Change From Baseline in Fasting VLDL-C [ Time Frame: Baseline, days 28, 56 and 84 ]
  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. Number of Participants Achieving LDL-C Reduction of ≥15% [ Time Frame: Days 28, 56 and 84 ]
  25. Number of Participants Achieving LDL-C Reduction of ≥20% [ Time Frame: Days 28, 56 and 84 ]
  26. Number of Participants Achieving LDL-C Reduction of ≥25% [ Time Frame: Days 28, 56 and 84 ]
  27. Number of Participants Achieving LDL-C Reduction of ≥30% [ Time Frame: Days 28, 56 and 84 ]
  28. Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) [ Time Frame: Days 28, 56 and 84 ]
  29. Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) [ Time Frame: Baseline, days 28, 56 and 84 ]
  30. Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) [ Time Frame: Baseline, days 28, 56 and 84 ]
  31. Percent Change From Baseline in Fibrinogen [ Time Frame: Baseline, days 28, 56 and 84 ]
  32. Change From Baseline in Fibrinogen [ Time Frame: Baseline, days 28, 56 and 84 ]
  33. Percent Change From Baseline in Fasting Lipoprotein(a) [ Time Frame: Baseline, days 28, 56 and 84 ]
  34. Change From Baseline in Fasting Lipoprotein(a) [ Time Frame: Baseline, days 28, 56 and 84 ]
  35. Percent Change From Baseline in Fasting Apolipoprotein B [ Time Frame: Baseline, days 28, 56 and 84 ]
  36. Change From Baseline in Fasting Apolipoprotein B [ Time Frame: Baseline, days 28, 56 and 84 ]
  37. Percent Change From Baseline in Fasting Apolipoprotein A-I [ Time Frame: Baseline, days 28, 56 and 84 ]
  38. Change From Baseline in Fasting Apolipoprotein A-I [ Time Frame: Baseline, days 28, 56 and 84 ]
  39. Percent Change From Baseline in Fasting Apolipoprotein A-II [ Time Frame: Baseline, days 28, 56 and 84 ]
  40. Change From Baseline in Fasting Apolipoprotein A-II [ Time Frame: Baseline, days 28, 56 and 84 ]
  41. Percent Change From Baseline in Fasting Apolipoprotein C-II [ Time Frame: Baseline, days 28, 56 and 84 ]
  42. Change From Baseline in Fasting Apolipoprotein C-II [ Time Frame: Baseline, days 28, 56 and 84 ]
  43. Percent Change From Baseline in Fasting Apolipoprotein C-III [ Time Frame: Baseline, days 28, 56 and 84 ]
  44. Change From Baseline in Fasting Apolipoprotein C-III [ Time Frame: Baseline, days 28, 56 and 84 ]
  45. Percent Change From Baseline in Fasting Apolipoprotein E [ Time Frame: Baseline, days 28, 56 and 84 ]
  46. Change From Baseline in Fasting Apolipoprotein E [ Time Frame: Baseline, days 28, 56 and 84 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   17 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02722408


Locations
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United States, California
Westside Medical Associates of Los Angeles
Beverly Hills, California, United States
Canada, Ontario
Robarts Research Institute
London, Ontario, Canada
Canada, Quebec
Ecogene-21
Chicoutimi, Quebec, Canada
Montreal Heart Institute
Montreal, Quebec, Canada
Israel
Wolfson Medical Center Internal Medicine Dept.
Holon, Israel
Center for Research, Prevention and Treatment of Atherosclerosis - Cardiology Department of Medicine Kiryat Hadassah
Jerusalem, Israel
Ziv Medical Center Internal Medicine Department
Safed, Israel
Sponsors and Collaborators
NeuroBo Pharmaceuticals Inc.
  Study Documents (Full-Text)

Documents provided by NeuroBo Pharmaceuticals Inc.:
Statistical Analysis Plan  [PDF] June 7, 2017
Study Protocol  [PDF] February 19, 2016

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: NeuroBo Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02722408    
Other Study ID Numbers: GEM-201
First Posted: March 30, 2016    Key Record Dates
Results First Posted: June 25, 2020
Last Update Posted: June 25, 2020
Last Verified: June 2020
Keywords provided by NeuroBo Pharmaceuticals Inc.:
LDL-C
Lipid Regulator
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias