Gemcabene for the Treatment of Pediatric NAFLD

NCT03436420 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB00099844
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, prospective, open-label, Phase 2, proof of concept study to test preliminary efficacy and safety of gemcabene in children with established nonalcoholic fatty liver disease (NAFLD) incompletely treated by lifestyle changes. The hypothesis of the study is that 300 mg of gemcabene once a day for 12 weeks will reduce alanine aminotransferase (ALT), hepatic steatosis, dyslipidemia and down regulate de novo lipogenesis in children with NAFLD.

Conditions

Non-Alcoholic Fatty Liver Disease

Keywords

Pediatrics; Lipids; Liver Diseases; Obesity

Outcome Measures

Primary Outcomes (1)

• Percent Change in Alanine Aminotransferase (ALT)

  Percent change in alanine aminotransferase (ALT) from baseline to 12 weeks was examined. ALT elevation is the most common screening test used for detecting NAFLD. The normal range for ALT varies by age, sex, and the specific assay used but is approximately 9-23 units/Liter (U/L) for boys and girls aged 1-18. Children with a sustained ALT ≥ 80 U/L are twice as likely to have nonalcoholic steatohepatitis (NASH), which is a severe form of NAFLD characterized by inflammation and liver cell damage.

  Baseline, Week 12

Secondary Outcomes (37)

• Absolute Change in ALT

  Baseline, Week 6, Week 12

• Percent Change in ALT Between Study Visits

  Baseline, Week 6, Week 12

• Absolute Change in Hepatic Steatosis

  Baseline, Week 12

• Absolute Change in Pancreatic Fat

  Baseline, Week 12

• Absolute Change in Aspartate Aminotransferase (AST)

  Baseline, Week 6, Week 12

Study Arms (1)

Gemcabene

EXPERIMENTAL

Children receiving 12 weeks of treatment with gemcabene

Drug: Gemcabene

Interventions

Gemcabene DRUG

Participants will take 300 milligrams (mg) of gemcabene, once per day for 12 weeks.

Also known as: Gemcabene calcium

Gemcabene

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Provision of signed and dated informed consent form
• Provision of signed and dated assent, if indicated
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Children aged 12-17 years at the time of informed consent
• History of clinical diagnosis of NAFLD including a, b and c below:
• Medical history eliminating, other chronic liver diseases (for example mitochondrial diseases, hepatotoxic drugs, anorexia nervosa)
• Laboratory studies: negative testing for hepatitis C and normal ceruloplasmin
• Either liver biopsy confirming NAFLD or MRI \> 10% steatosis within the past three years
• ALT ≥ 54 U/L for boys or ≥ 46 U/L for girls and ≤ 250 U/L at screening visit and within past three months (prior to screening). If ALT at screening is more than two times the historic value (or a historic value is not available), the subject will be asked to repeat the ALT after four weeks. If the repeat ALT is more than 50% increased or decreased over the screening ALT a third ALT may be obtained. If a third ALT is not within 50% of the previous value then the subject is ineligible, but may be rescreened at a later date.
• Body weight ≥ 60 kg at the time of screening
• Able to take oral medication and be willing to adhere to the study drug regimen
• Minimum of three months of attempted lifestyle modification to treat the NAFLD and agreement to adhere to Lifestyle Considerations (dietary improvement and physical activity) throughout study duration

You may not qualify if:

• Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias)
• Seizure disorder
• Active coagulopathy (international normalized ratio (INR) \> 1.4)
• Renal dysfunction with an estimated glomerular filtration rate (eGFR) \<60ml/min/1.73 calculated using Schwartz Bedside GFR calculator for children
• History of active malignant disease requiring chemotherapy or radiation
• History of significant alcohol intake (AUDIT questionnaire) or inability to quantify alcohol consumption
• Use of new medications or supplements with the intent to treat NAFLD/nonalcoholic steatohepatitis (NASH) during the 30 days prior to screening, including statin therapy. Medications or supplements (including metformin and vitamin E) that they have been on and are on a stable dose are acceptable
• History of bariatric surgery or planning to undergo bariatric surgery during study duration
• Clinically significant depression
• Any girl nursing, planning a pregnancy, known or suspected to be pregnant, or who has a positive pregnancy screen
• Non-compensated liver disease defined as cirrhosis and any one of the following hematologic, biochemical, and serological criteria on entry into protocol:
• Hemoglobin \< 10 g/dL;
• White blood cell (WBC) \< 3,500 cells/mm3;
• Neutrophil count \< 1,500 cells/mm3;
• Platelets \< 150,000 cells/mm3;

Sponsors & Collaborators

• Emory University: lead
• Gemphire Therapeutics: collaborator

Study Sites (1)

Children's Healthcare of Atlanta / Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Diseases; Obesity

Interventions

gemcabene

Condition Hierarchy (Ancestors)

Fatty Liver; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Miriam Vos, MD
• Organization: Emory University

mvos@emory.edu

404-727-9930

Study Officials

• Miriam B Vos, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 11, 2018
• First Posted: February 19, 2018
• Study Start: March 29, 2018
• Primary Completion: August 27, 2019
• Study Completion: August 27, 2019
• Last Updated: December 31, 2020
• Results First Posted: November 12, 2020

Record last verified: 2020-12

Locations

US (1)