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

Nonalcoholic Steatohepatitis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04565717
• Other study ID #: ALN-HSD-001
• Secondary ID: 2020-000847-29
• Status: Terminated
• Phase: Phase 1
• Start date: October 9, 2020
• Est. completion date: December 21, 2023

Study information

• Verified date: March 2024
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: December 21, 2023
• Est. primary completion date: January 6, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• NASH
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• ALN-HSD
ALN-HSD will be administered by subcutaneous (SC) injection.
• Placebo
Normal saline (0.9% NaCl) matching volume of ALN-HSD doses will be administered SC.

Locations

Country	Name	City	State
Belgium	Clinical Trial Site	Brussels
Bulgaria	Clinical Trial Site	Sofia
Turkey	Clinical Trial Site	Balçova
Turkey	Clinical Trial Site	Izmir
United Kingdom	Clinical Trial Site	Edinburgh
United Kingdom	Clinical Trial Site	London
United States	Clinical Trial Site	Baltimore	Maryland
United States	Clinical Trial Site	Fleming Island	Florida
United States	Clinical Trial Site	Hermitage	Tennessee
United States	Clinical Trial Site	Marrero	Louisiana
United States	Clinical Trial Site	San Antonio	Texas
United States	Clinical Trial Site	San Antonio	Texas
United States	Clinical Trial Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts A and B: Frequency of Adverse Events		Part A: Up to 3.5 months; Part B: up to 12.5 months
Primary	Part C: Change from Baseline of Liver Hydroxysteroid 17ß Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA)		Baseline and Month 6
Secondary	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
Secondary	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
Secondary	Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites		Part A and B: Day 1 up to 24 hours postdose
Secondary	Part B: Plasma Concentrations of ALN-HSD and Potential Major Metabolite(s)		Predose and up to 9 months postdose
Secondary	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
Secondary	Part C: Frequency of Adverse Events		Up to 6 months