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

NCT04565717 | Terminated Phase 1 FDA Drug

• 2 other identifiers: ALN-HSD-0012020-000847-29
• Study Type: interventional
• Target: 6
• Locations: 5 countries
• Sites: 13

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).

Conditions

Nonalcoholic Steatohepatitis; NASH

Keywords

Hepatobiliary disorders; Non-alcoholic fatty liver disease; NAFLD; Fatty liver; RNAi therapeutic

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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 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 B: Change from Baseline of Liver HSD17B13 mRNA

  Predose and up to 9 months postdose

Study Arms (5)

Part A: ALN-HSD

EXPERIMENTAL

Participants will be administered a single dose of ALN-HSD.

Drug: ALN-HSD

Part A: Placebo

PLACEBO COMPARATOR

Participants will be administered a single dose of ALN-HSD-matching placebo.

Drug: Placebo

Part B: ALN-HSD

EXPERIMENTAL

Participants will be administered multiple doses of ALN-HSD.

Drug: ALN-HSD

Part B: Placebo

PLACEBO COMPARATOR

Participants will be administered multiple doses of ALN-HSD-matching placebo.

Drug: Placebo

Part C: ALN-HSD

EXPERIMENTAL

Participants will be administered multiple doses of ALN-HSD.

Drug: ALN-HSD

Interventions

ALN-HSD DRUG

ALN-HSD will be administered by subcutaneous (SC) injection.

Part A: ALN-HSD; Part B: ALN-HSD; Part C: ALN-HSD

Placebo DRUG

Normal saline (0.9% NaCl) matching volume of ALN-HSD doses will be administered SC.

Part A: Placebo; Part B: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (13)

Clinical Trial Site

Fleming Island, Florida, 32003, United States

Location

Clinical Trial Site

Marrero, Louisiana, 70072, United States

Location

Clinical Trial Site

Baltimore, Maryland, 21202, United States

Location

Clinical Trial Site

Hermitage, Tennessee, 37076, United States

Location

Clinical Trial Site

San Antonio, Texas, 78215, United States

Location

Clinical Trial Site

San Antonio, Texas, 78229, United States

Location

Clinical Trial Site

San Antonio, Texas, 78230, United States

Location

Clinical Trial Site

Brussels, Belgium

Location

Clinical Trial Site

Sofia, Bulgaria

Location

Clinical Trial Site

Balçova, Turkey (Türkiye)

Location

Clinical Trial Site

Izmir, Turkey (Türkiye)

Location

Clinical Trial Site

Edinburgh, United Kingdom

Location

Clinical Trial Site

London, United Kingdom

Location

Related Publications (1)

• Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2025 Dec 12. doi: 10.1007/s40262-025-01606-0. Online ahead of print.

  PMID: 41388232 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Digestive System Diseases; Fatty Liver

Condition Hierarchy (Ancestors)

Liver Diseases

Study Officials

• Medical Director

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Parts A\&B: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Part C: Open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: September 25, 2020
• Study Start: October 9, 2020
• Primary Completion: January 6, 2023
• Study Completion: December 21, 2023
• Last Updated: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); TU (2); US (7); BU (1); GB (2)