NASH, Nonalcoholic Steatohepatitis
Conditions
Keywords
Hepatobiliary disorders, Non-alcoholic fatty liver disease, NAFLD, Fatty liver, RNAi therapeutic
Brief summary
The purpose of this study is to evaluate the safety and tolerability of single ascending doses of ALN-HSD in healthy participants (Part A) and multiple doses of ALN-HSD in patients with NASH (Parts B and C).
Interventions
DRUGPlacebo
Normal saline (0.9% NaCl) matching volume of ALN-HSD doses will be administered SC.
DRUGALN-HSD
ALN-HSD will be administered by subcutaneous (SC) injection.
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Parts A&B: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Part C: Open label
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Part A Only * Has body mass index (BMI) ≥18 kg/m\^2 and ≤28 kg/m\^2 * Has normal 12-lead electrocardiogram (ECG) * Parts B and C Only: * Has BMI ≥18 kg/m\^2 and ≤40 kg/m\^2 * Has a diagnosis of NASH documented in the patient's medical history or a clinical suspicion of NASH based on defined study criteria * Has screening liver biopsy with NASH activity score (NAS) score of ≥3 per NASH Clinical Research Network (CRN) criteria
Exclusion criteria
* Parts A, B and C: * Has any clinical safety laboratory result considered clinically significant and unacceptable by the Investigator * Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection * Has known history or evidence of drug abuse, within 12 months prior to screening * Has evidence of other forms of known chronic liver disease * Has recently received an investigational agent * Has any uncontrolled or serious disease, medical or surgical condition that my interfere with participation or data interpretation * Has excessive alcohol intake for ≥ 3 months during past year * Has history of intolerance to SC injection(s) * Has international normalized ratio (INR) \>1.2 * Has platelet count \<140x10\^9/L * Part A Only * Has systolic blood pressure (BP) \>140 mmHg and diastolic \>90 mmHg; * Has used certain prescription drugs within last 14 days prior to screening * Has used certain over the counter (OTC) medication within 7 days prior to screening * Has estimated glomerular filtration rate (GFR) \<90 mL/min/1.73m\^2 at screening * Parts B and C Only * Has abnormal ECG * Has changes in certain prescription medications defined in the protocol within the specified timeframe prior to screening * Has GFR\<45ml/min/1.73m\^2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts A and B: Frequency of Adverse Events | Part A: Up to 3.5 months; Part B: up to 12.5 months |
| Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA) | Baseline and Month 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites | Day 1 up to 24 hours postdose | — |
| Part B: Plasma Concentrations of ALN-HSD and Potential Major Metabolite(s) | Day 1 and Month 3 predose and up to 4 hours postdose | — |
| Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites | Day 1 predose and up to 48 hours postdose | — |
| Part C: Frequency of Adverse Events | Up to 6 months | — |
| Part B: Change from Baseline of Liver HSD17B13 mRNA | Predose and up to 9 months postdose | Hepatic HSD17B13 mRNA will be measured by quantitative reverse-transcription polymerase chain reaction using ribonucleic acid (RNA) isolated from liver biopsy. |
| Pat A: Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites | Day 1 predose and up to 48 hours postdose | — |
Countries
Belgium, Bulgaria, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed