Nonalcoholic SteatohepatitisPhase 1NCT04565717
A Study of ALN-HSD in Healthy Adult Subjects and Adult Patients With Nonalcoholic Steatohepatitis (NASH)
A Phase 1 study testing ALN-HSD in people with Nonalcoholic Steatohepatitis and NASH, run by Alnylam Pharmaceuticals at 13 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Nonalcoholic Steatohepatitis, NASH
- What is being tested?
- ALN-HSD
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 9 Oct 2020to 21 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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 locations and contacts
13 sites in 5 countries.
13 sites in 5 countries
United States7 sites
Clinical Trial Site
Baltimore, Maryland, 21202
Clinical Trial Site
Fleming Island, Florida, 32003
Clinical Trial Site
Hermitage, Tennessee, 37076
Clinical Trial Site
Marrero, Louisiana, 70072
Clinical Trial Site
San Antonio, Texas, 78215
Clinical Trial Site
San Antonio, Texas, 78229
Clinical Trial Site
San Antonio, Texas, 78230
Turkey (Türkiye)2 sites
Clinical Trial Site
Balçova
Clinical Trial Site
Izmir
United Kingdom2 sites
Clinical Trial Site
Edinburgh
Clinical Trial Site
London
About this study
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)
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).
- Conditions
- Nonalcoholic Steatohepatitis, NASH
- Being tested
- ALN-HSD, Placebo
- Keywords
- Hepatobiliary disorders, Non-alcoholic fatty liver disease, NAFLD, Fatty liver, RNAi therapeutic
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Digestive System Diseases, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-HSDDrug
ALN-HSD will be administered by subcutaneous (SC) injection.
PlaceboDrug
Normal saline (0.9% NaCl) matching volume of ALN-HSD doses will be administered SC.
| Study group | Role | What they receive |
|---|---|---|
| Part A: ALN-HSD | Experimental | Participants will be administered a single dose of ALN-HSD. Receives: Drug: ALN-HSD |
| Part A: Placebo | Placebo comparator | Participants will be administered a single dose of ALN-HSD-matching placebo. Receives: Drug: Placebo |
| Part B: ALN-HSD | Experimental | Participants will be administered multiple doses of ALN-HSD. Receives: Drug: ALN-HSD |
| Part B: Placebo | Placebo comparator | Participants will be administered multiple doses of ALN-HSD-matching placebo. Receives: Drug: Placebo |
| Part C: ALN-HSD | Experimental | Participants will be administered multiple doses of ALN-HSD. Receives: Drug: ALN-HSD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts A and B: Frequency of Adverse Events
Measured: Part A: Up to 3.5 months; Part B: up to 12.5 months
Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA)
Measured: Baseline and Month 6
Secondary outcomes (6)
Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites
Measured: Day 1 predose and up to 48 hours postdose
Pat A: Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites
Measured: Day 1 predose and up to 48 hours postdose
Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites
Measured: Day 1 up to 24 hours postdose
Part B: Plasma Concentrations of ALN-HSD and Potential Major Metabolite(s)
Measured: Day 1 and Month 3 predose and up to 4 hours postdose
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.
Measured: Predose and up to 9 months postdose
Part C: Frequency of Adverse Events
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start9 Oct 2020
- Primary completion6 Jan 2023
- Study completion21 Dec 2023
Why it stopped: Study ALN-HSD-001 was terminated due to business reasons and changes in the development strategy of the product. No safety issues were found.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04565717
- Sponsor's protocol ID
- ALN-HSD-001
- Other IDs
- 2020-000847-29
- Status last verified
- May 2024
- First submitted
- 21 Sep 2020
- Last updated
- 17 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12.
PubMed 41388232
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04565717
- Acronym / sponsor ID
- ALN-HSD-001
- Conditions
- Nonalcoholic Steatohepatitis, NASH
- Keywords
- Hepatobiliary disorders, Non-alcoholic fatty liver disease, NAFLD, Fatty liver, RNAi therapeutic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study ALN-HSD-001 was terminated due to business reasons and changes in the development strategy of the product. No safety issues were found.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2020 (actual)
- Primary completion
- 6 Jan 2023 (actual)
- Study completion
- 21 Dec 2023 (actual)
- First posted
- 25 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A: ALN-HSD | Experimental | Drug: ALN-HSDParticipants will be administered a single dose of ALN-HSD. |
| Part A: Placebo | Placebo comparator | Drug: PlaceboParticipants will be administered a single dose of ALN-HSD-matching placebo. |
| Part B: ALN-HSD | Experimental | Drug: ALN-HSDParticipants will be administered multiple doses of ALN-HSD. |
| Part B: Placebo | Placebo comparator | Drug: PlaceboParticipants will be administered multiple doses of ALN-HSD-matching placebo. |
| Part C: ALN-HSD | Experimental | Drug: ALN-HSDParticipants will be administered multiple doses of ALN-HSD. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Part A Only
- Parts B and C Only:
Key exclusion criteria (20 listed)
- Parts A, B and C:
- Part A Only
- Parts B and C Only
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALN-HSDALN-HSD will be administered by subcutaneous (SC) injection. | Drug | Part A: ALN-HSD, Part B: ALN-HSD, Part C: ALN-HSD |
| PlaceboNormal saline (0.9% NaCl) matching volume of ALN-HSD doses will be administered SC. | Drug | Part A: Placebo, Part B: Placebo |
Primary outcome
Parts A and B: Frequency of Adverse Events
Time frame: Part A: Up to 3.5 months; Part B: up to 12.5 months
Part C: Change from Baseline of Liver Hydroxysteroid 17β Dehydrogenase 13 (HSD17B13) Messenger Ribonucleic Acid (mRNA)
Time frame: Baseline and Month 6
6 secondary outcomes
Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites
Time frame: Day 1 predose and up to 48 hours postdose
Pat A: Maximum Plasma Concentration (Cmax) for ALN-HSD and Potential Metabolites
Time frame: Day 1 predose and up to 48 hours postdose
Part A: Fraction Excreted in Urine (fe) of ALN-HSD and Potential Metabolites
Time frame: Day 1 up to 24 hours postdose
Part B: Plasma Concentrations of ALN-HSD and Potential Major Metabolite(s)
Time frame: Day 1 and Month 3 predose and up to 4 hours postdose
Part B: Change from Baseline of Liver HSD17B13 mRNA
Time frame: Predose and up to 9 months postdose
Part C: Frequency of Adverse Events
Time frame: Up to 6 months
Results and safety
The study was stopped early (reason given: Study ALN-HSD-001 was terminated due to business reasons and changes in the development strategy of the product. No safety issues were found.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
- Derived from this study: PubMed 41388232Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Alnylam Pharmaceuticals
13 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALN-HSD in people with Nonalcoholic Steatohepatitis and NASH, run by Alnylam Pharmaceuticals at 13 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Turkey (Türkiye), United Kingdom, Belgium, Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study ALN-HSD-001 was terminated due to business reasons and changes in the development strategy of the product. No safety issues were found.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parts A and B: Frequency of Adverse Events (time frame: Part A: Up to 3.5 months; Part B: up to 12.5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04565717, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.