Clinical trial NCT02944383: A 12-Week Study to Assess the Efficacy Safety and Tolerability of Gemcabene in Subjects With Severe Hypertriglyceridemia
Official title: A 12-Week, Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy Safety and Tolerability of Gemcabene in Subjects With Severe Hypertriglyceridemia (INDIGO-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Severe Hypertriglyceridemia
Mixed Dyslipidaemia
Keywords: Hypertriglycerides
Lead sponsor: NeuroBo Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-25
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A 12-Week, Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy Safety and Tolerability of Gemcabene in Subjects with Severe Hypertriglyceridemia (INDIGO-1)


Eligibility criteria: Inclusion Criteria:

Subjects who meet all of the following criteria will be eligible to participate in the study:

1. Provision of written and signed informed consent (by subject or legal guardian) prior to any study-specific procedure;
2. Male or female (neither pregnant or lactating) ≥18 years of age at time of consent;

   1. Women of child-bearing potential must have a negative serum pregnancy test at the Screening Visit and negative urine dipstick on Study 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;
   2. 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.
3. Currently on a self-reported, stable, low-fat, low-cholesterol diet in combination with stable statins with or without ezetimibe (10 mg QD) for at least 12 weeks prior to the Screening Visit;
4. Mean fasting TG value ≥ 500 mg/dL to \< 1500 mg/dL (with the higher value no more than 50% greater than the lower value) from the S1 and S2 Visits (or alternatively S2 and S3);
5. Physical examination, including vital signs, that is within normal limits or clinically acceptable to the Investigator;
6. Weight ≥ 50 kg; with a body mass index (BMI) ≤ 45 kg/m²; and
7. Subjects with Type 2 diabetes who take anti-diabetes pharmacologic therapy must be on a stable a regimen for at least 3 months, with no planned changes in medications for the study duration.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from participation in the study:

1. Known and previously documented homozygous genetic deficiencies (LPL, ApoC-II, ApoC-III, ApoA-V, GPIHBP1, or LMF1);
2. History of pancreatitis within the last 6 months prior to screening (Visit S1);
3. History of bariatric surgery; symptomatic gallstone disease, unless treated with cholecystectomy;
4. Abnormal liver function test at the Pre-Screening Visit or any of the Screening Visits (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). Subjects 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;
5. Active liver disease (e.g., cirrhosis, alcoholic liver disease, hepatitis B \[HBV\], hepatitis C \[HCV\], autoimmune hepatitis, liver failure, liver cancer), history of liver transplant, known diagnosis of human immunodeficiency virus (HIV), or acquired immune deficiency virus;
6. Moderate to severe renal insufficiency defined as an estimated GFR \< 60 mL/min/1.73 m2 (calculated using The Chronic Kidney Disease Epidemiology Collaboration equation) at the Pre-Screening Visit or at any of the Screening Visits;
7. 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;
8. Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) below the lower limit of normal or \> 1.5 × ULN, respectively, based on results from the Pre-Screening Visit or the Screening Visit. If controlled, treatment should be stable for at least 3 months prior to the Screening Visit;
9. Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus HbA1c value ≥8.5% based on results from the Pre-Screening Visit or the Screening Visit), or any diabetic subject taking a thiazolidinedione (e.g., pioglitazone, rosiglitazone);
10. New York Heart Association Class III or IV heart failure (see Appendix C);
11. 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 (S1). Subjects with adequately treated stable angina, per Investigator assessment, may be included;
12. Uncontrolled cardiac arrhythmia or prolonged QT on the Screening Visit or Study 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;
13. Uncontrolled hypertension, defined as sitting systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg, and confirmed by repeat measurement;
14. Currently receiving cancer treatment(s) or, in the Investigator's opinion, at risk of relapse for recent cancer;
15. Inadequate washout of a PCSK9 inhibitor (8 weeks prior to the Screening Visit S1), a fibrate lipid lowering agent (6 weeks prior to the Screening Visit S1), niacin \> 200 mg/day, OMG-3, bile acid sequestrants or other lipid lowering therapies (4 weeks prior to the Screening Visit S1);
16. Use of any excluded medications or supplements within 3 months prior to S1 (e.g., potent cytochrome P450 \[CYP\] 3A4 inhibitors, see Appendix D);
17. Hypersensitivity to or a history of significant adverse reactions to any fibrate lipid regulating agent;
18. History of drug or alcohol abuse within the past year or inability to comply with protocol requirements, including subject alcohol restrictions (see Section 5.6.3);
19. Previously treated with gemcabene (i.e., CI-1027); 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
20. Any other finding which, in the opinion of the Investigator, would compromise the subject's safety or participation in the study.

Primary outcomes:
measure: Percent Change From Baseline to End of Study (EOS) in Fasting Serum Triglycerides (TG)
timeFrame: Baseline, EOS (average of week 10 and 12)
Secondary outcomes:
measure: Percent Change From Baseline in Fasting Serum TG
timeFrame: Baseline, Weeks 2, 6, 10 and 12
measure: Change From Baseline in Fasting Serum TG
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in TC
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in TC
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Non-HDL-C
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Non-HDL-C
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in VLDL-C
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in VLDL-C
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in HDL-C
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in HDL-C
timeFrame: Baseline, Weeks 2, 6, 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Apolipoprotein B
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Apolipoprotein B
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Apolipoprotein A-I
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Apolipoprotein A-I
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Apolipoprotein A-II
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Apolipoprotein A-II
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Apolipoprotein C-II
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Apolipoprotein C-II
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Apolipoprotein C-III
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Apolipoprotein C-III
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Apolipoprotein E
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Apolipoprotein E
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in LDL-C
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in LDL-C
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in LDL-TG
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in LDL-TG
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in VLDL-TG
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in VLDL-TG
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in HDL-TG
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in HDL-TG
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Lipoprotein Size
timeFrame: Baseline, Week 12
measure: Change From Baseline in Lipoprotein Size
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Lipoprotein Particle Number
timeFrame: Baseline, Week 12
measure: Change From Baseline in Lipoprotein Particle Number
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in HDL Particle Number
timeFrame: Baseline, Week 12
measure: Change From Baseline in HDL Particle Number
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in High-sensitivity C-reactive Protein
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in High-sensitivity C-reactive Protein
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Fibrinogen
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Fibrinogen
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Serum Amyloid A
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Serum Amyloid A
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Adiponectin
timeFrame: Baseline, Week 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Adiponectin
timeFrame: Baseline, Week 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Angiopoietin 4
timeFrame: Baseline, Week 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Angiopoietin 4
timeFrame: Baseline, Week 12 and EOS (average of week 10 and 12)
measure: Percent Change From Baseline in Interleukin-6
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Change From Baseline in Interleukin-6
timeFrame: Baseline, Weeks 10, 12 and EOS (average of week 10 and 12)
measure: Percentage of Participants Achieving a TG Value < 500 mg/dL (5.65 mmol/L)
timeFrame: Weeks 10, 12 and EOS (average of week 10 and 12)
Other outcomes:
Locations:
city: Fort Payne
country: United States
facility: Appalachian Research Associates
state: Alabama
city: Tucson
country: United States
facility: Del Sol Research Mangagement, LLC
state: Arizona
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles
state: California
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Garden Grove
country: United States
facility: SC Clinical Research
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: San Diego
country: United States
facility: Paradigm Clinical Research
state: California
city: Wheat Ridge
country: United States
facility: Paradigm Research
state: Colorado
city: Boca Raton
country: United States
facility: Excel Medical Research
state: Florida
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Hialeah
country: United States
facility: Direct Helpers Research Center
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Lauderdale Lakes
country: United States
facility: Sunrise Medical Research
state: Florida
city: Miami Lakes
country: United States
facility: AR Developoment Solutions
state: Florida
city: Miami
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami
country: United States
facility: Millenium Clinical Research, Inc.
state: Florida
city: Miami
country: United States
facility: Medcare Research
state: Florida
city: West Palm Beach
country: United States
facility: Soma Medical Research
state: Florida
city: Evanston
country: United States
facility: Evanston Premier Clinical Research
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research, Inc.
state: Indiana
city: Junction City
country: United States
facility: Richard Lochamy, M.D.
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Covington
country: United States
facility: Clinical Trials Management, LLC
state: Louisiana
city: Metairie
country: United States
facility: Clinical Trials Management, LLC
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: Jackson
country: United States
facility: Elite Clinical Research
state: Mississippi
city: Las Vegas
country: United States
facility: Clinical Research of South Nevada
state: Nevada
city: Bronx
country: United States
facility: CHEAR Center, LLC
state: New York
city: Bronx
country: United States
facility: Advantage Clinical Trials
state: New York
city: Benson
country: United States
facility: Eastern Carolina Medical Clinic
state: North Carolina
city: Farmville
country: United States
facility: Physicians East, NA
state: North Carolina
city: Greenville
country: United States
facility: Physicians East, NA
state: North Carolina
city: Morrisville
country: United States
facility: Cary Medical Clinic
state: North Carolina
city: Columbus
country: United States
facility: Optimed Research
state: Ohio
city: Dayton
country: United States
facility: PriMed Clinical Research
state: Ohio
city: Lansdale
country: United States
facility: Green and Seidner Family Practice Associates
state: Pennsylvania
city: Lincoln
country: United States
facility: BTC of Lincoln
state: Rhode Island
city: Rock Hill
country: United States
facility: Carolinas Research Partners, LLC
state: South Carolina
city: Houston
country: United States
facility: Airline Complete Healthcare
state: Texas
city: Kerrville
country: United States
facility: Sante Clinical Research
state: Texas
city: Lampasas
country: United States
facility: FMC Science
state: Texas
city: Plano
country: United States
facility: Clinical Investigations of Texas
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Kenosha
country: United States
facility: Clinical Investigation Specialists
state: Wisconsin
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
Study officials:
affiliation: NeuroBo Pharmaceuticals Inc.
name: Lee Golden, MD
role: STUDY_DIRECTOR
References: