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

Sponsor

Alnylam Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04565717

Collaborator

(none)

103

Enrollment

Locations

Arms

26.8

Anticipated Duration (Months)

4.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

103 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 :

Oct 9, 2020

Anticipated Primary Completion Date :

Jan 4, 2023

Anticipated Study Completion Date :

Jan 4, 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

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

Secondary Outcome Measures

Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites [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]
Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites [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]
Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites [Part A and B: Day 1 up to 24 hours postdose]
Part B: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA) [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

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Huntington Park	California	United States	90255
2	Clinical Trial Site	Newport Beach	California	United States	92660
3	Clinical Trial Site	Fleming Island	Florida	United States	32003
4	Clinical Trial Site	Inverness	Florida	United States	34452
5	Clinical Trial Site	Maitland	Florida	United States	32751
6	Clinical Trial Site	Miami	Florida	United States	33135
7	Clinical Trial Site	Marrero	Louisiana	United States	70072
8	Clinical Trial Site	Baltimore	Maryland	United States	21202
9	Clinical Trial Site	Jackson	Mississippi	United States	39216
10	Clinical Trial Site	Hermitage	Tennessee	United States	37076
11	Clinical Trial Site	Arlington	Texas	United States	76012
12	Clinical Trial Site	San Antonio	Texas	United States	78215
13	Clinical Trial Site	San Antonio	Texas	United States	78229
14	Clinical Trial Site	San Antonio	Texas	United States	78230
15	Clinical Trial Site	Temple	Texas	United States	76508
16	Clinical Trial Site	Brussels		Belgium
17	Clinical Trial Site	Sofia		Bulgaria
18	Clinical Trial Site	Stara Zagora		Bulgaria
19	Clinical Trial Site	Balçova		Turkey
20	Clinical Trial Site	Edinburgh		United Kingdom
21	Clinical Trial Site	London		United Kingdom