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Trial record 1 of 1 for:    NCT04565717
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A Study of ALN-HSD in Healthy Adult Subjects and Adult Patients With Nonalcoholic Steatohepatitis (NASH)

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

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

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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

Resource links provided by the National Library of Medicine


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.




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.



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04565717


Contacts
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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
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United Kingdom
Clinical Trial Site Recruiting
London, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: Medical Director Alnylam Pharmaceuticals
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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    Key Record Dates
Last Update Posted: March 25, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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