Study of Aldafermin (NGM282) in Participants With Impaired Hepatic Function

Study Overview
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Brief Summary
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This is an evaluation of Aldafermin (NGM282) in an open-label, single-dose and parallel group study in participants with Impaired Hepatic Function

Official Title
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A Phase I, Open-label, Parallel-group Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Dose of Aldafermin in Subjects With Impaired Hepatic Function

Conditions
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Impaired Hepatic Function

Intervention / Treatment
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* Biological: Aldafermin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, 18 - 75 years of age, inclusive Able to comprehend and willing to sign an informed consent form (ICF) Willing and able to comply with all study requirements BMI 18 - 40 kg/m2, inclusive at Screening Stable medication regimen - no medication initiation or dose change within 7 days or 5 half-lives (whichever is longer) prior to dosing of the study medication. Non-pregnant, non-lactating females. Female subjects of childbearing potential and male subjects with a female sexual partner of childbearing potential must agree to consistent and adequate birth control. One of the following forms of contraception is required: Condom Hormone containing contraceptive Intrauterine device with a failure rate < 1% per year Cervical cap or diaphragm with spermicidal agent Tubal sterilization Vasectomy in male partner Sexual abstinence Negative test for drugs of abuse at Screening unless they are currently prescribed Negative human immunodeficiency virus (HIV) antibody screen at Screening Exclusion Criteria: Any acute disease or condition being treated by medical therapy (prescription or over the counter) known to possibly impact hepatic function History of or recent (< 6 weeks) treatment for a chronic condition with a medication that is known to have hepatotoxic potential. Any significant physical injury or surgical procedure within 6 weeks of Screening Uncontrolled diabetes (hemoglobin A1c [HbA1c] > 9.5%) Uncontrolled hypertension (systolic blood pressure [SBP] > 180 mmHg on ≥ 3 medications of different classes for blood pressure control) Have received any investigational medication within 30 days or 5 half-lives, whichever is longer, prior to study dosing Subjects should not have donated blood within 60 days of study entry or plasma within 7 days of study entry. Subjects must also refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following the last dose of study medication. Positive urine drug screen at Screening that is not otherwise explained by a permitted concomitant medication History of alcoholism in the 6 months prior to Screening Inadequate peripheral venous access

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Child-Pugh A (Mild Hepatic Impairment) & Healthy Matched<br>Administered by subcutaneous injection | Biological: Aldafermin<br>* Biological: Aldafermin (NGM282) Subcutaneous Injection<br>* Other names: NGM282;|
| Experimental: Child-Pugh B (Moderate Hepatic Impairment) & Healthy Matched<br>Administered by subcutaneous injection | Biological: Aldafermin<br>* Biological: Aldafermin (NGM282) Subcutaneous Injection<br>* Other names: NGM282;|
| Experimental: Child-Pugh C (Severe Hepatic Impairment) & Healthy Matched<br>Administered by subcutaneous injection | Biological: Aldafermin<br>* Biological: Aldafermin (NGM282) Subcutaneous Injection<br>* Other names: NGM282;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of a single dose aldafermin | Maximum observed plasma concentration (Cmax) of aldafermin (Day 1 through Day 4) | 4 days | 
| Pharmacokinetics of a single dose of aldafermin | Area under the concentration-time curve from time zero extrapolated to infinity (AUC infinity) of aldafermin (Day 1 through Day 4) | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type and frequency of adverse events (Day 1 through Day 11) | Frequency, severity, timing, and/or duration of treatment-emergent adverse events (TEAE) and serious adverse events (SAEs) | 11 days |