A Study of ALN-HSD in Healthy Adult Subjects and Adult Patients With Nonalcoholic Steatohepatitis (NASH)
- Registration Number
- NCT04565717
- Lead Sponsor
- Alnylam Pharmaceuticals
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 6
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part C: ALN-HSD ALN-HSD Participants will be administered multiple doses of ALN-HSD. Part A: ALN-HSD ALN-HSD Participants will be administered a single dose of ALN-HSD. Part A: Placebo Placebo Participants will be administered a single dose of ALN-HSD-matching placebo. Part B: ALN-HSD ALN-HSD Participants will be administered multiple doses of ALN-HSD. Part B: Placebo Placebo Participants will be administered multiple doses of ALN-HSD-matching placebo.
- Primary Outcome Measures
Name Time Method Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA) Baseline and Month 6 Parts A and B: Frequency of Adverse Events Part A: Up to 3.5 months; Part B: up to 12.5 months
- Secondary Outcome Measures
Name Time Method 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 C: Frequency of Adverse Events Up to 6 months Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites Day 1 up to 24 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 Pat A: Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites Day 1 predose and up to 48 hours postdose 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.
Trial Locations
- Locations (1)
Clinical Trial Site
🇬🇧London, United Kingdom