Clinical trial NCT04565717: A Study of ALN-HSD in Healthy Adult Subjects and Adult Patients With Nonalcoholic Steatohepatitis (NASH)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Nonalcoholic Steatohepatitis
NASH
Keywords: Hepatobiliary disorders
Non-alcoholic fatty liver disease
NAFLD
Fatty liver
RNAi therapeutic
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Parts A and B: Frequency of Adverse Events
timeFrame: Part A: Up to 3.5 months; Part B: up to 12.5 months
measure: Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA)
timeFrame: Baseline and Month 6
Secondary outcomes:
measure: Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites
timeFrame: Day 1 predose and up to 48 hours postdose
measure: Pat A: Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites
timeFrame: Day 1 predose and up to 48 hours postdose
measure: Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites
timeFrame: Day 1 up to 24 hours postdose
measure: Part B: Plasma Concentrations of ALN-HSD and Potential Major Metabolite(s)
timeFrame: Day 1 and Month 3 predose and up to 4 hours postdose
measure: Part B: Change from Baseline of Liver HSD17B13 mRNA
timeFrame: Predose and up to 9 months postdose
measure: Part C: Frequency of Adverse Events
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Fleming Island
country: United States
facility: Clinical Trial Site
state: Florida
city: Marrero
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Hermitage
country: United States
facility: Clinical Trial Site
state: Tennessee
city: San Antonio
country: United States
facility: Clinical Trial Site
state: Texas
city: San Antonio
country: United States
facility: Clinical Trial Site
state: Texas
city: San Antonio
country: United States
facility: Clinical Trial Site
state: Texas
city: Brussels
country: Belgium
facility: Clinical Trial Site
city: Sofia
country: Bulgaria
facility: Clinical Trial Site
city: Balçova
country: Turkey
facility: Clinical Trial Site
city: İzmir
country: Turkey
facility: Clinical Trial Site
city: Edinburgh
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: