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A Trial to Learn if Having 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

Primary Purpose

Nonalcoholic Steatohepatitis, Genetic Risk Factor

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
ALN-PNP Dose Level 1
ALN-PNP Dose Level 2
ALN-PNP Dose Level 3
Matching Placebo
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nonalcoholic Steatohepatitis focused on measuring NASH, Nonalcoholic Fatty Liver Disease, NAFLD

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: 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 or heterozygotes; 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: 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 a screening, as defined in the protocol History of Type 1 diabetes Bariatric surgery within approximately 5 years prior or planned during the study period 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Cohort 1

    Cohort 2

    Arm Description

    Participants who are homozygous for the PNPLA3 risk allele (G/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo

    Participants who are heterozygous for the PNPLA3 risk allele (C/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo

    Outcomes

    Primary Outcome Measures

    Incidence of treatment-emergent adverse events (TEAEs)
    Severity of TEAEs

    Secondary Outcome Measures

    Change in liver fat fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in participants with NAFLD
    Change in Low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD
    Change in High-density lipoprotein cholesterol (HDL-C) in participants with NAFLD
    Change in Triglycerides (TG) in participants with NAFLD
    Change in Lipoprotein a (Lp(a)) in participants with NAFLD
    Change in Apolipoprotein A1 (ApoA1) in participants with NAFLD
    Change in Apolipoprotein B (ApoB) in participants with NAFLD
    Concentration of ALN-PNP and potential major metabolite(s) in plasma over time
    Incidence of anti-drug antibodies (ADAs) to ALN-PNP
    Titer of anti-drug antibodies (ADAs) to ALN-PNP

    Full Information

    First Posted
    August 16, 2023
    Last Updated
    September 5, 2023
    Sponsor
    Regeneron Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06024408
    Brief Title
    A Trial to Learn if Having 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
    Official Title
    A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending 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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 24, 2023 (Anticipated)
    Primary Completion Date
    January 8, 2026 (Anticipated)
    Study Completion Date
    January 8, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Regeneron Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The study is researching an experimental drug called ALN-PNP. The study is focused on participants who are known to have non-alcoholic fatty liver disease (NAFLD), and a specific variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene. 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 How ALN-PNP 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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Nonalcoholic Steatohepatitis, Genetic Risk Factor
    Keywords
    NASH, Nonalcoholic Fatty Liver Disease, NAFLD

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    96 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Cohort 1
    Arm Type
    Experimental
    Arm Description
    Participants who are homozygous for the PNPLA3 risk allele (G/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo
    Arm Title
    Cohort 2
    Arm Type
    Experimental
    Arm Description
    Participants who are heterozygous for the PNPLA3 risk allele (C/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo
    Intervention Type
    Drug
    Intervention Name(s)
    ALN-PNP Dose Level 1
    Intervention Description
    Administered by subcutaneous (SC) injection, every 4 weeks (Q4W) x 4 doses
    Intervention Type
    Drug
    Intervention Name(s)
    ALN-PNP Dose Level 2
    Intervention Description
    Administered SC, Q4w x 4 doses
    Intervention Type
    Drug
    Intervention Name(s)
    ALN-PNP Dose Level 3
    Intervention Description
    Administered SC, Q4W x 4 doses
    Intervention Type
    Drug
    Intervention Name(s)
    Matching Placebo
    Intervention Description
    Administered SC, Q4W x 4 doses
    Primary Outcome Measure Information:
    Title
    Incidence of treatment-emergent adverse events (TEAEs)
    Time Frame
    Through End of Study (EOS), Up to 253 days
    Title
    Severity of TEAEs
    Time Frame
    Through EOS, Up to 253 days
    Secondary Outcome Measure Information:
    Title
    Change in liver fat fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in participants with NAFLD
    Time Frame
    Baseline up to 169 days
    Title
    Change in Low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD
    Time Frame
    Baseline up to 253 days
    Title
    Change in High-density lipoprotein cholesterol (HDL-C) in participants with NAFLD
    Time Frame
    Baseline up to 253 days
    Title
    Change in Triglycerides (TG) in participants with NAFLD
    Time Frame
    Baseline up to 253 days
    Title
    Change in Lipoprotein a (Lp(a)) in participants with NAFLD
    Time Frame
    Baseline up to 253 days
    Title
    Change in Apolipoprotein A1 (ApoA1) in participants with NAFLD
    Time Frame
    Baseline up to 253 days
    Title
    Change in Apolipoprotein B (ApoB) in participants with NAFLD
    Time Frame
    Baseline up to 253 days
    Title
    Concentration of ALN-PNP and potential major metabolite(s) in plasma over time
    Time Frame
    Up to 253 days
    Title
    Incidence of anti-drug antibodies (ADAs) to ALN-PNP
    Time Frame
    Up to 253 days
    Title
    Titer of anti-drug antibodies (ADAs) to ALN-PNP
    Time Frame
    Up to 253 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Key Inclusion Criteria: 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 or heterozygotes; 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: 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 a screening, as defined in the protocol History of Type 1 diabetes Bariatric surgery within approximately 5 years prior or planned during the study period 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Clinical Trials Administrator
    Phone
    844-734-6643
    Email
    clinicaltrials@regeneron.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Clinical Trial Management
    Organizational Affiliation
    Regeneron Pharmaceuticals
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
    IPD Sharing Time Frame
    When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
    IPD Sharing Access Criteria
    Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
    IPD Sharing URL
    https://vivli.org/

    Learn more about this trial

    A Trial to Learn if Having 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

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