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

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

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

Study Overview

• Status: Completed
• Conditions: Impaired Hepatic Function
• Intervention / Treatment: Biological: Aldafermin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • NGM Clinical Study Site 110
    • Orlando, Florida, United States, 32809
      • NGM Clinical Study Site 111
  • Texas
    • San Antonio, Texas, United States, 78215
      • NGM Clinical Study Site 113

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females, 18 - 75 years of age, inclusive
2. Able to comprehend and willing to sign an informed consent form (ICF)
3. Willing and able to comply with all study requirements
4. BMI 18 - 40 kg/m2, inclusive at Screening
5. 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.

6. 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:

   1. Condom
   2. Hormone containing contraceptive
   3. Intrauterine device with a failure rate < 1% per year
   4. Cervical cap or diaphragm with spermicidal agent
   5. Tubal sterilization
   6. Vasectomy in male partner
   7. Sexual abstinence
7. Negative test for drugs of abuse at Screening unless they are currently prescribed
8. Negative human immunodeficiency virus (HIV) antibody screen at Screening

Exclusion Criteria:

1. Any acute disease or condition being treated by medical therapy (prescription or over the counter) known to possibly impact hepatic function
2. History of or recent (< 6 weeks) treatment for a chronic condition with a medication that is known to have hepatotoxic potential.
3. Any significant physical injury or surgical procedure within 6 weeks of Screening
4. Uncontrolled diabetes (hemoglobin A1c [HbA1c] > 9.5%)
5. Uncontrolled hypertension (systolic blood pressure [SBP] > 180 mmHg on ≥ 3 medications of different classes for blood pressure control)
6. Have received any investigational medication within 30 days or 5 half-lives, whichever is longer, prior to study dosing
7. 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.
8. Positive urine drug screen at Screening that is not otherwise explained by a permitted concomitant medication
9. History of alcoholism in the 6 months prior to Screening
10. Inadequate peripheral venous access

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics (PD) of biomarker 7-alpha-hydroxy-4-cholesten-3-one (C4)	Absolute change from baseline	6 and 24 hours post dose
Pharmacodynamics (PD) of biomarker 7-alpha-hydroxy-4-cholesten-3-one (C4)	Percent change from baseline	6 and 24 hours post dose

Collaborators and Investigators

• Sponsor: NGM Biopharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): November 19, 2021
• Study Completion (Actual): November 19, 2021

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 15, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 282-HI-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No