Phase 3 N=169 Randomized Triple-blind Treatment

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

Nonalcoholic Fatty Liver Disease (NAFLD)

Bottom Line

View on ClinicalTrials.gov: NCT01529268 ↗

Enrolled (actual)

169

Serious AEs

5.3%

Results posted

Sep 2017

Primary outcome: Primary: Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) — 25; 18 participants — p=0.34

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: DR cysteamine bitartrate capsule (Drug); DR cysteamine bitartrate placebo (Other)
Age: Pediatric · 8+ yrs
Sex: All
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Primary completion: Mar 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Improvement in Nonalcoholic Fatty Liver Disease (NAFLD)	25; 18	0.34
SECONDARY Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)	-0.8; -0.8	0.90
SECONDARY Steatosis: Patients With Improvement	26; 33	0.15
SECONDARY Steatosis: Change in Score	-0.3; -0.4	0.59
SECONDARY Lobular Inflammation: Patients With Improvement	32; 17	0.03 sig
SECONDARY Lobular Inflammation: Change in Score	-0.4; -0.1	0.06
SECONDARY Hepatocellular Ballooning: Patients With Improvement	17; 21	0.29
SECONDARY Hepatocellular Ballooning: Change in Score	-0.1; -0.3	0.15
SECONDARY Portal Inflammation: Patients With Improvement	18; 14	0.57
SECONDARY Portal Inflammation: Change in Score	-0.1; -0.1	0.76
SECONDARY Fibrosis: Patients With Improvement	25; 23	0.98
SECONDARY Fibrosis: Change in Stage	-0.3; -0.1	0.24
SECONDARY Resolution of NASH	4; 2	0.29
SECONDARY Change in Serum Aminotransferase and Gamma-glutamyl Transpeptidase	-53; -8; -31; -4; -10; -1	0.02 sig
SECONDARY Change in Weight (kg)	6.3; 7.8	0.25
SECONDARY Change in Body-mass Index	0.8; 1.1	0.42
SECONDARY Change in Body-mass Index Z-score	-0.1; 0	0.11
SECONDARY Change in Waist Circumference	2.5; 2.3	0.89
SECONDARY Change in Fasting Serum Glucose	1; 5	0.24
SECONDARY Change in Fasting Insulin	6; 10	0.34
SECONDARY Change in HOMA-IR	1.4; 3.6	0.15
SECONDARY Change in Systolic Blood Pressure	3; 2	0.71
SECONDARY Change in Diastolic Blood Pressure	-1; 1	0.31
SECONDARY Change in Pediatric Quality of Life Inventory (PedsQL) Score	4; 5; 4; 5; 4; 5	0.77
SECONDARY Reduction in MRI-determined Hepatic Fat Fraction	-5.3; -2.6	0.11

Summary

CyNCh is a multi-center, placebo-controlled clinical trial of children ages 8 to 17 years with biopsy-confirmed moderate to severe nonalcoholic fatty liver disease (NAFLD). The primary objective is to evaluate whether 52 weeks of treatment with cysteamine bitartrate delayed-release capsules will result in improvement in liver disease severity.

Eligibility Criteria

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 1.0 mg/dL
Total bilirubin >3 mg/dL
Albumin 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01529268). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.