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

Alnylam Pharmaceuticals

Status and phase: Terminated; Phase 1

Conditions: NASH; Nonalcoholic Steatohepatitis

Treatments: Drug: Placebo; Drug: ALN-HSD

Study type: Interventional

Funder types: Industry

Identifiers

NCT04565717

2020-000847-29 (EudraCT Number)

ALN-HSD-001

Details and patient eligibility

About

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).

Enrollment: 6 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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6 participants in 5 patient groups, including a placebo group

Part A: ALN-HSD

Experimental group

Description:

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

Treatment:

Drug: ALN-HSD

Part A: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Part B: ALN-HSD

Experimental group

Description:

Participants will be administered multiple doses of ALN-HSD.

Treatment:

Drug: ALN-HSD

Part B: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Part C: ALN-HSD

Experimental group

Description:

Participants will be administered multiple doses of ALN-HSD.

Treatment:

Drug: ALN-HSD