NCT04565717TerminatedPhase 1
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, 3-Part Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Dose ALN-HSD in Healthy Adult Subjects and Multiple Dose ALN-HSD in Adult Patients With Nonalcoholic Steatohepatitis (NASH)
Alnylam Pharmaceuticals1 site in 1 country6 target enrollmentStarted: October 9, 2020Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA)
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Parts A&B: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Part C: Open label
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
Part A: ALN-HSD
Experimental
Participants will be administered a single dose of ALN-HSD.
Intervention: ALN-HSD (Drug)
Part A: Placebo
Placebo Comparator
Participants will be administered a single dose of ALN-HSD-matching placebo.
Intervention: Placebo (Drug)
Part B: ALN-HSD
Experimental
Participants will be administered multiple doses of ALN-HSD.
Intervention: ALN-HSD (Drug)
Part B: Placebo
Placebo Comparator
Participants will be administered multiple doses of ALN-HSD-matching placebo.
Intervention: Placebo (Drug)
Part C: ALN-HSD
Experimental
Participants will be administered multiple doses of ALN-HSD.
Intervention: ALN-HSD (Drug)
Outcomes
Primary Outcomes
Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA)
Time Frame: Baseline and Month 6
Parts A and B: Frequency of Adverse Events
Time Frame: Part A: Up to 3.5 months; Part B: up to 12.5 months
Secondary Outcomes
- 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)
Investigators
Study Sites (1)
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