A Multiple Ascending Dose Study of Pegozafermin in Participants With Biopsy Confirmed Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH

89bio

Status and phase: Completed; Phase 2; Phase 1

Conditions: NASH

Treatments: Other: Placebo; Drug: Pegozafermin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04048135

BIO89-100-002

Details and patient eligibility

About

Part 1: This is a multi-center evaluation of pegozafermin (administered weekly or every other week) in a randomized, double-blind, placebo-controlled study administered for 12 weeks in participants with NASH and NAFLD at high risk of NASH, including a pre-defined number of participants with biopsy confirmed NASH and fibrosis stages F1-F3 to be enrolled.

Part 2: This is a multi-center, open label evaluation of pegozafermin at 27 mg administered weekly for 20 weeks in participants with biopsy-proven NASH (NAS ≥4, fibrosis stage F2 or F3).

Enrollment: 101 patients

Sex: All

Ages: 21 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participants must be 21 to 75 years of age inclusive, at the time of signing the informed consent form (ICF).
• Evidence of steatosis by Fibroscan and magnetic resonance imaging based proton density fat fraction (MRI-PDFF)
• NASH or NAFLD at high risk for NASH as reflected by AT LEAST ONE of the following:
• Diagnosis of NASH with fibrosis (stages F1, F2 or F3), without cirrhosis, by percutaneous liver biopsy within 24 months prior to screening
• Central obesity WITH type 2 diabetes mellitus (T2DM)
• Central obesity WITH either increased alanine transaminase (ALT) and/or Fibroscan vibration-controlled transient elastography (VCTE) score ≥7 KPa.
• Part 2 only: Biopsy-proven NASH in a liver biopsy obtained within 24 weeks of baseline with fibrosis stage F2 or F3 and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation. A small number of high risk F1 allowed.

Key Exclusion Criteria:

• Clinically significant disorder or a history of any illness that, in the opinion of the Investigator, might confound the results of the study, or pose additional risk to the participant by participation in the study.
• History of type 1 diabetes.
• Weight loss of more than 5% within 3 months prior to Day -1 or more than 10% within 6 months prior to Day -1 or planning to try to lose weight during conduct of study.
• History of a liver disorder other than NASH or clinical suspicion of a liver disorder other than NASH
• History of cirrhosis or evidence of cirrhosis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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101 participants in 8 patient groups, including a placebo group

Part 1: Pegozafermin 3 milligrams (mg) weekly (QW)

Experimental group

Description:

Participants were administered 3 mg of pegozafermin QW, via subcutaneous (SC) injection, starting on Day 1 through Day 85.

Treatment:

Drug: Pegozafermin

Part 1: Pegozafermin 9 mg QW

Experimental group

Description:

Participants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.

Treatment:

Drug: Pegozafermin

Part 1: Pegozafermin 18 mg QW

Experimental group

Description:

Participants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.

Treatment:

Drug: Pegozafermin

Part 1: Pegozafermin 27 mg QW

Experimental group

Description:

Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.

Treatment:

Drug: Pegozafermin

Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W)

Experimental group

Description:

Participants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.

Treatment:

Drug: Pegozafermin

Part 1: Pegozafermin 36 mg Q2W

Experimental group

Description:

Participants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.

Treatment:

Drug: Pegozafermin

Part 1: Placebo QW or Q2W

Placebo Comparator group

Description:

Participants were administered placebo matching to pegozafermin QW or Q2W, via SC injection, starting on Day 1 through Day 85.

Treatment:

Other: Placebo

Part 2: Pegozafermin 27 mg QW

Experimental group

Description:

Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134.

Treatment:

Drug: Pegozafermin