Nonalcoholic Fatty Liver Disease (NAFLD)Phase 1NCT06024408
A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor
A Phase 1 study testing ALN-PNP in people with Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH), run by Regeneron Pharmaceuticals at 5 sites in South Korea.
Trial summary
This study is researching an experimental drug called ALN-PNP. This study is focused on participants who are known to have nonalcoholic fatty liver disease (NAFLD), and a specific variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), Genetic Risk Factor
- What is being tested?
- ALN-PNP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 5 sitesSouth Korea
- Study dates
- 21 May 2024to 7 Jul 2025
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants from 18 (or country's legal age of adulthood) to 65 years of age, inclusive, at screening visit 1
- Body mass index (BMI) from 23.0 kg/m^2 to 40.0 kg/m^2, inclusive, for East Asians (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and BMI from 27.0 kg/m^2 to 40.0 kg/m^2, inclusive, for any other ethnicity at screening visit 1
- Meets genotype criteria for the rs738409:G PNPLA3 risk allele: homozygotes (for Part A and Part B) or heterozygotes (optional Part C); p.I148M variant (PNPLA3 rs738409:G [p.I148M]) at screening visit 1
- Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3
- Generally stable diet (based on participant's recall) for at least 3 months prior to the screening visit
Who cannot join
- Evidence of other forms of known chronic liver disease, as defined in the protocol
- Has a contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made out of metal (for example, cochlear implant, nerve stimulators, magnetic vascular clips, and metallic heart valve), severe claustrophobia, or other contraindications for MRI
- Is taking a medication to treat a co-morbid condition that is not permitted during the study
- Has any laboratory parameter assessments at screening, as defined in the protocol
- History of Type 1 diabetes
- Bariatric surgery within approximately 5 years prior or planned during the study period
Show all 10Show fewer
- Has lost or gained more than 4.0% body weight over the 3 months prior to or during the screening period
- Has known human immunodeficiency virus (HIV) infection, evidence of current or chronic hepatitis B virus (HBV) infection, or current or chronic hepatitis C virus (HCV) infection, as defined in the protocol
- Was hospitalized (ie, >24 hours) for any reason within 30 days of the screening visit
- Note: Other protocol defined Inclusion/Exclusion Criteria apply
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
South Korea5 sites
Chungbuk National University Hospital
Cheongju-si, Chungcheong Buk-do, 28644
CHA Bundang Medical Center
Seongnam-si, Gyeonggi-do, 13496
Seoul National University Hospital
Seoul, 03080
Severance Hospital
Seoul, 03722
Asan Medical Center
Seoul, 05505
About this study
Official title: A Three-Part, Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALN-PNP siRNA in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a PNPLA3 Genetic Risk Factor
This study is researching an experimental drug called ALN-PNP. This study is focused on participants who are known to have nonalcoholic fatty liver disease (NAFLD), and a specific variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene.
The aim of this study is to see how safe, tolerable, and effective the study drug is.
Read more
This study is looking at several other research questions, including:
- What side effects may happen from taking the study drug
- How the study drug works to change liver fat content in NAFLD
- How much study drug and study drug metabolites (byproduct of the body breaking down the study drug) are in your blood at different times
- Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
- Better understanding of the study drug and NAFLD
- Conditions
- Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), Genetic Risk Factor
- Being tested
- ALN-PNP, Placebo
- Keywords
- Homozygous, Heterozygous
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-PNPDrug
Part A: Administered as single subcutaneous (SC) injection on day 1 Part B and Part C: Administered SC every 12 weeks (Q12W x2)
PlaceboDrug
Part A: Administered as single SC injection on day 1 Part B and Part C: Administered SC every 12 weeks (Q12W x2)
| Study group | Role | What they receive |
|---|---|---|
| Part A: Placebo | Placebo comparator | Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 Receives: Drug: Placebo |
| Part A: Low Dose | Experimental | Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 Receives: Drug: ALN-PNP |
| Part A: Mid Dose | Experimental | Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 Receives: Drug: ALN-PNP |
| Part A: High Dose | Experimental | Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 Receives: Drug: ALN-PNP |
| Part B: Placebo | Placebo comparator | Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 Receives: Drug: Placebo |
| Part B : Low Dose | Experimental | Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 Receives: Drug: ALN-PNP |
| Part B: Mid Dose | Experimental | Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 Receives: Drug: ALN-PNP |
| Part B: High Dose | Experimental | Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 Receives: Drug: ALN-PNP |
| Part C: Placebo (Optional) | Placebo comparator | Sponsor may elect to enroll participants who are heterozygous for the PNPLA3 rs738409:G risk allele and may be randomized 1:1 Receives: Drug: Placebo |
| Part C: High Dose (Optional) | Experimental | Sponsor may elect to enroll participants who are heterozygous for the PNPLA3 rs738409:G risk allele and may be randomized 1:1 Receives: Drug: ALN-PNP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events (TEAEs)
Measured: Up to 253 days
Severity of TEAEs
Measured: Up to 253 days
Secondary outcomes (10)
Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDFF) in participants with NAFLD
Measured: Baseline up to 253 days
Change in low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD
Measured: Baseline up to 253 days
Change in high-density lipoprotein cholesterol (HDL-C) in participants with NAFLD
Measured: Baseline up to 253 days
Change in triglycerides (TG) in participants with NAFLD
Measured: Baseline up to 253 days
Change in lipoprotein a (Lp(a)) in participants with NAFLD
Measured: Baseline up to 253 days
Change in apolipoprotein A1 (ApoA1) in participants with NAFLD
Measured: Baseline up to 253 days
Change in apolipoprotein B (ApoB) in participants with NAFLD
Measured: Baseline up to 253 days
Concentration of ALN-PNP and potential major metabolite(s) in plasma over time
Measured: Up to 253 days
Incidence of anti-drug antibodies (ADAs) to ALN-PNP
Measured: Up to 253 days
Titer of anti-drug antibodies (ADAs) to ALN-PNP
Measured: Up to 253 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2023
- Study start21 May 2024
- Primary completion7 Jul 2025
- Study completion7 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonalcoholic Fatty Liver Disease (NAFLD)Studies of the same condition, open and under way.
- More trials run by Regeneron 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
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06024408
- Sponsor's protocol ID
- ALN-PNP-NASH-2255
- Status last verified
- Jul 2025
- First submitted
- 16 Aug 2023
- Last updated
- 31 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Three-Part, Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALN-PNP siRNA in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a PNPLA3 Genetic Risk Factor
- ClinicalTrials.gov ID
- NCT06024408
- Acronym / sponsor ID
- ALN-PNP-NASH-2255
- Conditions
- Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), Genetic Risk Factor
- Keywords
- Homozygous, Heterozygous
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 May 2024 (actual)
- Primary completion
- 7 Jul 2025 (actual)
- Study completion
- 7 Jul 2025 (actual)
- First posted
- 6 Sep 2023 (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.
This study is researching an experimental drug called ALN-PNP. This study is focused on participants who are known to have nonalcoholic fatty liver disease (NAFLD), and a specific variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene.
The aim of this study is to see how safe, tolerable, and effective the study drug is.
This study is looking at several other research questions, including:
- What side effects may happen from taking the study drug
- How the study drug works to change liver fat content in NAFLD
- How much study drug and study drug metabolites (byproduct of the body breaking down the study drug) are in your blood at different times
- Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
- Better understanding of the study drug and NAFLD
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Part A: Placebo | Placebo comparator | Drug: PlaceboParticipants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 |
| Part A: Low Dose | Experimental | Drug: ALN-PNPParticipants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 |
| Part A: Mid Dose | Experimental | Drug: ALN-PNPParticipants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 |
| Part A: High Dose | Experimental | Drug: ALN-PNPParticipants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 |
| Part B: Placebo | Placebo comparator | Drug: PlaceboParticipants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 |
| Part B : Low Dose | Experimental | Drug: ALN-PNPParticipants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 |
| Part B: Mid Dose | Experimental | Drug: ALN-PNPParticipants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 |
| Part B: High Dose | Experimental | Drug: ALN-PNPParticipants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1 |
| Part C: Placebo (Optional) | Placebo comparator | Drug: PlaceboSponsor may elect to enroll participants who are heterozygous for the PNPLA3 rs738409:G risk allele and may be randomized 1:1 |
| Part C: High Dose (Optional) | Experimental | Drug: ALN-PNPSponsor may elect to enroll participants who are heterozygous for the PNPLA3 rs738409:G risk allele and may be randomized 1:1 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participants from 18 (or country's legal age of adulthood) to 65 years of age, inclusive, at screening visit 1
- Body mass index (BMI) from 23.0 kg/m^2 to 40.0 kg/m^2, inclusive, for East Asians (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and BMI from 27.0 kg/m^2 to 40.0 kg/m^2, inclusive, for any other ethnicity at screening visit 1
- Meets genotype criteria for the rs738409:G PNPLA3 risk allele: homozygotes (for Part A and Part B) or heterozygotes (optional Part C); p.I148M variant (PNPLA3 rs738409:G [p.I148M]) at screening visit 1
- Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3
- Generally stable diet (based on participant's recall) for at least 3 months prior to the screening visit
Key exclusion criteria (10 listed)
- Evidence of other forms of known chronic liver disease, as defined in the protocol
- Has a contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made out of metal (for example, cochlear implant, nerve stimulators, magnetic vascular clips, and metallic heart valve), severe claustrophobia, or other contraindications for MRI
- Is taking a medication to treat a co-morbid condition that is not permitted during the study
- Has any laboratory parameter assessments at screening, as defined in the protocol
- History of Type 1 diabetes
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-PNPPart A: Administered as single subcutaneous (SC) injection on day 1 Part B and Part C: Administered SC every 12 weeks (Q12W x2) | Drug | Part A: High Dose, Part A: Low Dose, Part A: Mid Dose, Part B : Low Dose, Part B: High Dose, Part B: Mid Dose, Part C: High Dose (Optional) |
| PlaceboPart A: Administered as single SC injection on day 1 Part B and Part C: Administered SC every 12 weeks (Q12W x2) | Drug | Part A: Placebo, Part B: Placebo, Part C: Placebo (Optional) |
Primary outcome
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: Up to 253 days
Severity of TEAEs
Time frame: Up to 253 days
10 secondary outcomes
Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDFF) in participants with NAFLD
Time frame: Baseline up to 253 days
Change in low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD
Time frame: Baseline up to 253 days
Change in high-density lipoprotein cholesterol (HDL-C) in participants with NAFLD
Time frame: Baseline up to 253 days
Change in triglycerides (TG) in participants with NAFLD
Time frame: Baseline up to 253 days
Change in lipoprotein a (Lp(a)) in participants with NAFLD
Time frame: Baseline up to 253 days
Change in apolipoprotein A1 (ApoA1) in participants with NAFLD
Time frame: Baseline up to 253 days
Change in apolipoprotein B (ApoB) in participants with NAFLD
Time frame: Baseline up to 253 days
Concentration of ALN-PNP and potential major metabolite(s) in plasma over time
Time frame: Up to 253 days
Incidence of anti-drug antibodies (ADAs) to ALN-PNP
Time frame: Up to 253 days
Titer of anti-drug antibodies (ADAs) to ALN-PNP
Time frame: Up to 253 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
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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.
Clinical Trial Management study director
Regeneron Pharmaceuticals
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALN-PNP in people with Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH), run by Regeneron Pharmaceuticals at 5 sites in South Korea.
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 5 inclusion and 10 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: finished, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in South Korea. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of treatment-emergent adverse events (TEAEs) (time frame: Up to 253 days). 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?
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 31 Jul 2025.