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Healthy VolunteersPhase 1/2NCT05648214

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

A Phase 1/2 study testing ALN-PNP in people with Healthy Volunteers and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), run by Regeneron Pharmaceuticals at 6 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This study is researching an experimental drug called ALN-PNP (called "study drug"). This is a first in human study. The study drug is not approved by any public health agency such as the United States Food and Drug Administration (FDA) for any kind of treatment. This study consists of 3 parts. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
What is being tested?
ALN-PNP
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
172 participants
Where
6 sitesUnited States
Study dates
27 Dec 2022to 10 Aug 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Part A (Healthy Adults):
  • From 18 to 55 years of age
  • For Japanese cohorts ONLY; the Japanese participant must:
  • Be Japanese, born in Japan, and have both biologic parents and 4 biologic grandparents who are ethnically Japanese and born in Japan
  • Have maintained a Japanese lifestyle, with no significant change since leaving Japan, including having access to Japanese food and adhering to a Japanese diet
  • Be living <10 years outside of Japan
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  • Has a Body Mass Index (BMI) between 18 and 32 kg/m^2, inclusive, at the screening visit
  • Is judged by the investigator to be in good health, as described in the protocol
  • Is in good health based on laboratory safety testing obtained at the screening visit and approximately within 24 hours prior to administration of study drug
  • Part B and Part C (Participants with MASLD):
  • Part B: From 18 to 65 years of age
  • Part C: From 18 to 75 years of age
  • BMI from 23.0 kg/m2 to 40.0 kg/m2, inclusive, for East Asians (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and BMI from 27.0 kg/m2 to 40.0 kg/m2, inclusive, for any other ethnicity at screening visit 1
  • Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3

Who cannot join

  • Part A:
  • History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, neurological, or dermatologic disease, as assessed by the investigator, that may confound the results of the study or poses an additional risk to the participant by study participation
  • Presents any concern to the study investigator that might confound the results of the study or poses an additional risk to the participant by their participation in the study
  • Hospitalized for any reason within 30 days of the screening visit
  • Using the Modification of Diet in Renal Disease equation, has a glomerular filtration rate as described in the protocol at the screening visit
  • Has Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) or total bilirubin above the Upper Limit of Normal (ULN) range
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  • Is a current smoker or former smoker, including e-cigarettes, who stopped smoking within 3 months prior to the screening visit
  • Has a history of alcohol or drug abuse per investigator opinion
  • Is positive for hepatitis C antibody and if so, positive for qualitative (ie, detected or not detected) Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) test at the screening visit
  • Part B and Part C:
  • Evidence of other forms of known chronic liver disease, as defined in the protocol
  • Has a contraindication to MRI examinations, as defined in the protocol
  • History of Type 1 diabetes
  • 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 HCV infection, as defined in the protocol
  • Bariatric surgery within approximately 5 years (Part B) or 3 years (Part C) prior or planned during the study period
  • NOTE: Other protocol defined inclusion / exclusion criteria apply

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Clinical Trials Administrator contact

844-734-6643

clinicaltrials@regeneron.com

6 sites in 1 country

United States6 sites, 5 recruiting

  • California Clinical Trials Medical Group

    Glendale, California, 91206

    Completed

  • Pioneer Research Solutions

    Houston, Texas, 77099

    Recruiting

  • Velocity Clinical research

    Los Angeles, California, 90057

    Recruiting

  • Tandem Clinical Research

    Marrero, Louisiana, 70072

    Recruiting

  • Genoma Research Group, Inc

    Miami, Florida, 33173

    Recruiting

  • Med Research of Florida, LLC

    Miami, Florida, 33186

    Recruiting

Other trials in United States

About this study

Official title: A Three-Part, Phase 1/2a, Randomized, Double-blind, Placebo-Controlled, Single and Multiple Dose Study of the Safety, Tolerability, and Pharmacokinetics of ALN-PNP, an siRNA Targeting PNPLA3, in Healthy Adults and Adult Participants With MASLD

This study is researching an experimental drug called ALN-PNP (called "study drug"). This is a first in human study. The study drug is not approved by any public health agency such as the United States Food and Drug Administration (FDA) for any kind of treatment.

This study consists of 3 parts. Part A is focused on healthy participants. Parts B and C of the study are focused on participants who are known to have MASLD and a specific variant of the PNPLA3 gene.

Read more

The aim of the study is to see how safe, tolerable and effective the study drug is.

The study is looking at several other research questions, including:

  • What side effects may happen from taking the study drug (Parts A, B and C)
  • How much study drug (Parts A, B and C) and study drug metabolites (byproduct of the body breaking down the study drug) (Parts B and C) are in the blood at different times
  • Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects) (Part A, B and C)
  • Explore impact of Japanese ethnicity on safety and PK (Pharmacokinetics, or study of what the body does to the drug) of single doses of ALN-PNP over time (Part A)
  • How the study drug works to change liver fat content in MASLD (Part B and C)
  • Better understanding of the study drug and MASLD (Part B and C)
Being tested
ALN-PNP, Placebo (PB)
Keywords
Liver steatosis, Fibrosis, Hepatocytes, Non-Alcoholic Steatohepatitis (NASH), Non-Alcoholic Fatty Liver Disease (NAFLD), Metabolic dysfunction-Associated Steatohepatitis (MASH)
Medical subject headings
Fatty Liver, Fibrosis, 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

    Administered per the protocol

  • Placebo (PB)Drug

    Administered per the protocol

Study groups in NCT05648214
Study groupRoleWhat they receive
Part A: CohortsExperimentalNot described
Receives: Drug: ALN-PNP; Drug: Placebo (PB)
Part A: Optional CohortExperimentalNot described
Receives: Drug: ALN-PNP; Drug: Placebo (PB)
Part A: JPN CohortsExperimentalNot described
Receives: Drug: ALN-PNP; Drug: Placebo (PB)
Part B: CohortsExperimentalNot described
Receives: Drug: ALN-PNP; Drug: Placebo (PB)
Part C: CohortsExperimentalNot described
Receives: Drug: ALN-PNP; Drug: Placebo (PB)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Treatment-Emergent Adverse Events (TEAEs)

    Measured: Up to Day 337

  2. Severity of TEAEs

    Measured: Up to Day 337

Secondary outcomes (13)

  1. Concentration of ALN-PNP and potential major metabolite(s) in plasma

    Measured: Up to Day 337

  2. Incidence of Anti-Drug Antibodies (ADAs) to ALN-PNP

    Measured: Up to Day 337

  3. Magnitude of ADAs to ALN-PNP

    Measured: Up to Day 337

  4. Change in Low-Density Lipoprotein (LDL)

    Part A

    Measured: Baseline up to Day 169

  5. Change in High-Density Lipoprotein (HDL)

    Part A

    Measured: Baseline up to Day 169

  6. Change in TriGlyceride (TG)

    Measured: Baseline up to Day 337

  7. Change in Apolipoprotein B (ApoB)

    Measured: Baseline up to Day 337

  8. Change in liver fat fraction by Magnetic Resonance Imaging derived Proton-Density Fat Fraction (MRI-PDFF)

    Part B and Part C

    Measured: Baseline up to Day 253

  9. Change in Low-Density Lipoprotein Cholesterol (LDL-C)

    Part B and Part C

    Measured: Baseline up to Day 337

  10. Change in High-Density Lipoprotein Cholesterol (HDL-C)

    Part B and Part C

    Measured: Baseline up to Day 337

  11. Change in Lipoprotein (a) (Lp[a])

    Part B and Part C

    Measured: Baseline up to Day 337

  12. Change in Apolipoprotein A1 (ApoA1)

    Part B and Part C

    Measured: Baseline up to Day 337

  13. Change in small dense Low-Density Lipoprotein (sdLDL)

    Part C

    Measured: Baseline up to Day 337

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2022
  2. Study start27 Dec 2022
  3. Primary completion10 Aug 2027 (estimated)
  4. Study completion10 Aug 2027 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Phase 1: Part A (Sequential Ascending Dose) and Part B (Parallel Assignment) Phase 2a: Part C (Parallel Assignment)
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
172 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05648214
Sponsor's protocol ID
ALN-PNP-HV-2227
Status last verified
Apr 2026
First submitted
5 Dec 2022
Last updated
16 Apr 2026
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.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ALN-PNP in people with Healthy Volunteers and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), run by Regeneron Pharmaceuticals at 6 sites in United States.

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 14 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Clinical Trials Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. 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 Day 337). 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 NCT05648214.

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 16 Apr 2026.

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