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

Primary Purpose

Nonalcoholic Steatohepatitis, NASH

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ALN-HSD
Placebo
Sponsored by
Alnylam Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nonalcoholic Steatohepatitis focused on measuring Hepatobiliary disorders, Non-alcoholic fatty liver disease, NAFLD, Fatty liver, RNAi therapeutic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts 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)

  • 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

Sites / Locations

  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
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  • Clinical Trial Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Part A: ALN-HSD

Part A: Placebo

Part B: ALN-HSD

Part B: Placebo

Part C: ALN-HSD

Arm Description

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

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

Participants will be administered multiple doses of ALN-HSD.

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

Participants will be administered multiple doses of ALN-HSD.

Outcomes

Primary Outcome Measures

Parts A and B: Frequency of Adverse Events
Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA)

Secondary Outcome Measures

Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites
Pat A: Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites
Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites
Part B: Plasma Concentrations of ALN-HSD and Potential Major Metabolite(s)
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.
Part C: Frequency of Adverse Events

Full Information

First Posted
September 21, 2020
Last Updated
October 20, 2023
Sponsor
Alnylam Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04565717
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 9, 2020 (Actual)
Primary Completion Date
May 29, 2024 (Anticipated)
Study Completion Date
May 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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 (Parts B and C).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Steatohepatitis, NASH
Keywords
Hepatobiliary disorders, Non-alcoholic fatty liver disease, NAFLD, Fatty liver, RNAi therapeutic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Parts A&B: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Part C: Open label
Allocation
Randomized
Enrollment
114 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A: ALN-HSD
Arm Type
Experimental
Arm Description
Participants will be administered a single dose of ALN-HSD.
Arm Title
Part A: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be administered a single dose of ALN-HSD-matching placebo.
Arm Title
Part B: ALN-HSD
Arm Type
Experimental
Arm Description
Participants will be administered multiple doses of ALN-HSD.
Arm Title
Part B: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be administered multiple doses of ALN-HSD-matching placebo.
Arm Title
Part C: ALN-HSD
Arm Type
Experimental
Arm Description
Participants will be administered multiple doses of ALN-HSD.
Intervention Type
Drug
Intervention Name(s)
ALN-HSD
Intervention Description
ALN-HSD will be administered by subcutaneous (SC) injection.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal saline (0.9% NaCl) matching volume of ALN-HSD doses will be administered SC.
Primary Outcome Measure Information:
Title
Parts A and B: Frequency of Adverse Events
Time Frame
Part A: Up to 3.5 months; Part B: up to 12.5 months
Title
Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA)
Time Frame
Baseline and Month 6
Secondary Outcome Measure Information:
Title
Part A: 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
Title
Pat A: 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
Title
Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites
Time Frame
Part A and B: Day 1 up to 24 hours postdose
Title
Part B: Plasma Concentrations of ALN-HSD and Potential Major Metabolite(s)
Time Frame
Predose and up to 9 months postdose
Title
Part B: Change from Baseline of Liver HSD17B13 mRNA
Description
Hepatic HSD17B13 mRNA will be measured by quantitative reverse-transcription polymerase chain reaction using ribonucleic acid (RNA) isolated from liver biopsy.
Time Frame
Predose and up to 9 months postdose
Title
Part C: Frequency of Adverse Events
Time Frame
Up to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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) ≤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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Fleming Island
State/Province
Florida
ZIP/Postal Code
32003
Country
United States
Facility Name
Clinical Trial Site
City
Marrero
State/Province
Louisiana
ZIP/Postal Code
70072
Country
United States
Facility Name
Clinical Trial Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Facility Name
Clinical Trial Site
City
Hermitage
State/Province
Tennessee
ZIP/Postal Code
37076
Country
United States
Facility Name
Clinical Trial Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Clinical Trial Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Clinical Trial Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78230
Country
United States
Facility Name
Clinical Trial Site
City
Brussels
Country
Belgium
Facility Name
Clinical Trial Site
City
Sofia
Country
Bulgaria
Facility Name
Clinical Trial Site
City
Balçova
Country
Turkey
Facility Name
Clinical Trial Site
City
İzmir
Country
Turkey
Facility Name
Clinical Trial Site
City
Edinburgh
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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