Cysteamine Bitartrate Delayed-Release for the Treatment of NAFLD in Children

Inclusion criteria

• Children age 8-17 years
• Liver biopsy obtained within 90 days of screening visit and not more than 120 days before randomization
• Clinical history consistent with nonalcoholic fatty liver disease (NAFLD)
• Definite NAFLD based upon liver histology
• No evidence of any other liver disease by clinical history or histological evaluation
• A histological severity of: NAFLD Activity Score (NAS) ≥ 4.
• Sexually active female participants of childbearing potential (i.e., not surgically sterile [defined as tubal ligation, hysterectomy, or bilateral oophorectomy]) must agree to utilize the same two acceptable forms of contraception from screening through completion of the study and to complete a serum pregnancy test at each study visit. The acceptable forms of contraception for this study include hormonal contraceptives (oral, implant, transdermal patch, or injection) at a stable dose for at least 3 months prior to screening, and barrier (condom with spermicide, diaphragm with spermicide). Sexual activity will be ascertained at each study visit for post-menarchal females and if sexually active, subject must verify use of the same 2 acceptable forms of contraception. For pre-pubescent children, a documented attestation of abstinence from their parent or guardian will be acceptable.
• Participants must be able to swallow DR Cysteamine tablets with the tablet intact
• Written informed consent from parent or legal guardian
• Written informed assent from the child

Exclusion criteria

• There will be no exclusion criteria based on race, ethnicity or gender.
• Participants with a current history of the following conditions or any other health issues that make it unsafe for them to participate in the opinion of the Investigators:

• Inflammatory bowel disease (if currently active) or prior resection of small intestine
• Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias)
• Seizure disorder
• Active coagulopathy
• Gastrointestinal ulcers/bleeding
• Renal dysfunction with a creatinine clearance < 90 mL/min/m2
• History of active malignant disease requiring chemotherapy within the past 12 months prior to randomization
• History of significant alcohol intake (AUDIT questionnaire) or inability to quantify alcohol consumption
• Chronic use (more than 2 consecutive weeks) of medications known to cause hepatic steatosis or steatohepatitis (systemic glucocorticoids, tetracycline, anabolic steroids, valproic acid, salicylates, tamoxifen) in the past year.
• The use of other known hepatotoxins within 90 days of liver biopsy or within 120 days of randomization
• Initiation of medications with the intent to treat NAFLD/NASH in the time period following liver biopsy and prior to randomization
• History of total parenteral nutrition (TPN) use in year prior to screening
• History of bariatric surgery or planning to undergo bariatric surgery during study duration
• Clinically significant depression (patients hospitalized for suicidal ideations or suicide attempts within the past 12 months)
• Any female nursing, planning a pregnancy, known or suspected to be pregnant, or who has a positive serum pregnancy screen.
• Non-compensated liver disease with 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 of blood;
• Neutrophil count < 1,500 cells/mm3 of blood;
• Platelets < 130,000 cells/mm3 of blood;
• Direct bilirubin > 1.0 mg/dL
• Total bilirubin >3 mg/dL
• Albumin < 3.2 g/dL
• International normalized ratio (INR) > 1.4
• Poorly controlled diabetes mellitus (hemoglobin A1c (HbA1c) > 9%)
• Evidence of other chronic liver disease:

• Biopsy consistent with histological evidence of autoimmune hepatitis
• Serum hepatitis B surface antigen (HBsAg) positive.
• Serum hepatitis C antibody (anti-HCV) positive.
• Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) > 45% with histological evidence of iron overload
• Alpha-1-antitrypsin (A1AT) phenotype ZZ or SZ
• Wilson's disease
• Children who are currently enrolled in a clinical trial or who received an investigational study drug within 180 days of screening or liver biopsy.
• Subjects who are not able or willing to comply with the protocol or have any other condition that would impede compliance or hinder completion of the study, in the opinion of the investigator.
• Failure to give informed consent