A Study of ALN-HSD in Healthy Adult Subjects and Adult Patients With Nonalcoholic Steatohepatitis (NASH)

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)

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 Overview

• Status: Terminated
• Conditions: Nonalcoholic Steatohepatitis; NASH
• Intervention / Treatment: Drug: ALN-HSD; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alnylam Clinical Trial Information Line; Phone Number: 1-877-ALNYLAM; Email: clinicaltrials@alnylam.com
• Study Contact Backup: Name: Alnylam Clinical Trial Information Line; Phone Number: 1-877-256-9526; Email: clinicaltrials@alnylam.com

Study Locations

• Belgium
  • Brussels, Belgium
    • Clinical Trial Site
• Bulgaria
  • Sofia, Bulgaria
    • Clinical Trial Site
• Turkey
  • Balçova, Turkey
    • Clinical Trial Site
  • İzmir, Turkey
    • Clinical Trial Site
• United Kingdom
  • Edinburgh, United Kingdom
    • Clinical Trial Site
  • London, United Kingdom
    • Clinical Trial Site
• United States
  • Florida
    • Fleming Island, Florida, United States, 32003
      • Clinical Trial Site
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Clinical Trial Site
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Clinical Trial Site
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Clinical Trial Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trial Site
    • San Antonio, Texas, United States, 78215
      • Clinical Trial Site
    • San Antonio, Texas, United States, 78230
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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) ≤60 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: ALN-HSD; Participants will be administered a single dose of ALN-HSD.	Drug: ALN-HSD; ALN-HSD will be administered by subcutaneous (SC) injection.
Placebo Comparator: Part A: Placebo; Participants will be administered a single dose of ALN-HSD-matching placebo.	Drug: Placebo; Normal saline (0.9% NaCl) matching volume of ALN-HSD doses will be administered SC.
Experimental: Part B: ALN-HSD; Participants will be administered multiple doses of ALN-HSD.	Drug: ALN-HSD; ALN-HSD will be administered by subcutaneous (SC) injection.
Placebo Comparator: Part B: Placebo; Participants will be administered multiple doses of ALN-HSD-matching placebo.	Drug: Placebo; Normal saline (0.9% NaCl) matching volume of ALN-HSD doses will be administered SC.
Experimental: Part C: ALN-HSD; Participants will be administered multiple doses of ALN-HSD.	Drug: ALN-HSD; ALN-HSD will be administered by subcutaneous (SC) injection.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites		Part A: Day 1 predose and up to 48 hours postdose; Part B: Day 1 and Month 3 predose and up to 4 hours postdose
Pat A: Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites		Part A: Day 1 predose and up to 48 hours postdose; Part B: Day 1 and Month 3 predose and up to 4 hours postdose
Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites		Part A and B: Day 1 up to 24 hours postdose
Part B: Plasma Concentrations of ALN-HSD and Potential Major Metabolite(s)		Predose and up to 9 months postdose
Part B: Change from Baseline of Liver HSD17B13 mRNA	Hepatic HSD17B13 mRNA will be measured by quantitative reverse-transcription polymerase chain reaction using ribonucleic acid (RNA) isolated from liver biopsy.	Predose and up to 9 months postdose
Part C: Frequency of Adverse Events		Up to 6 months

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Investigators: Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2020
• Primary Completion (Actual): January 6, 2023
• Study Completion (Actual): December 21, 2023

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Non-alcoholic fatty liver disease; NAFLD; RNAi therapeutic; Fatty liver; Hepatobiliary disorders
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ALN-HSD-001; 2020-000847-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No