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

• ClinicalTrials.gov Identifier: NCT04565717
• Recruitment Status: Recruiting
• First Posted: September 25, 2020
• Last Update Posted: March 25, 2021
• Sponsor: Alnylam Pharmaceuticals
• Information provided by (Responsible Party): Alnylam Pharmaceuticals

Study Description

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 (Part B).

Condition or disease	Intervention/treatment	Phase
Nonalcoholic Steatohepatitis; NASH	Drug: ALN-HSD; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, 2-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)
• Actual Study Start Date: October 9, 2020
• Estimated Primary Completion Date: May 31, 2023
• Estimated Study Completion Date: June 30, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Frequency of Adverse Events [ Time Frame: Part A: Up to 3.5 months; Part B: up to 12.5 months ]

Secondary Outcome Measures :

1. Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites [ Time Frame: 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 ]
2. Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites [ Time Frame: 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 ]
3. Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites [ Time Frame: Part A and B: Day 1 up to 24 hours postdose ]
4. Part B: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA) [ Time Frame: Predose and up to 9 months postdose ]
   Hepatic HSD17B13 mRNA will be measured by quantitative reverse-transcription polymerase chain reaction using ribonucleic acid (RNA) isolated from liver biopsy.

Eligibility Criteria

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

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)

• Part B 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 and B:

  • 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

• Part B 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

Contacts and Locations

Contacts

Contact: Alnylam Clinical Trial Information Line; 1-877-ALNYLAM; clinicaltrials@alnylam.com

Contact: Alnylam Clinical Trial Information Line; 1-877-256-9526; clinicaltrials@alnylam.com

Locations

United Kingdom

Clinical Trial Site; Recruiting

London, United Kingdom

Sponsors and Collaborators

Alnylam Pharmaceuticals

Investigators

• Study Director: Medical Director; Alnylam Pharmaceuticals

More Information

• Responsible Party: Alnylam Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04565717
• Other Study ID Numbers: ALN-HSD-001; 2020-000847-29 ( EudraCT Number )
• First Posted: September 25, 2020
• Last Update Posted: March 25, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alnylam Pharmaceuticals:

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

Additional relevant MeSH terms:

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