Study Evaluating the Safety, Efficacy and Tolerability of BIO89-100 in Subjects With Biopsy-confirmed Nonalcoholic Steatohepatitis (NASH) (ENLIVEN)
December 16, 2025 updated by: 89bio, Inc.
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of BIO89-100 in Subjects With Biopsy-Confirmed Nonalcoholic Steatohepatitis (NASH)
This is a randomized, double-blind, placebo-controlled study that will evaluate the safety, efficacy, tolerability of BIO89-100 in patients with biopsy-confirmed fibrosis stages F2-F3 NASH.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
222
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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San Juan, Puerto Rico, 00927
- 89bio Clinical Study Site
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Alabama
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Birmingham, Alabama, United States, 35209
- 89bio Clinical Study Site
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Birmingham, Alabama, United States, 35211
- 89bio Clinical Study Site
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Dothan, Alabama, United States, 36305
- 89bio Clinical Study Site
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Guntersville, Alabama, United States, 35976
- 89bio Clinical Study Site
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Madison, Alabama, United States, 35758
- 89bio Clinical Study Site
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Arizona
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Chandler, Arizona, United States, 85224
- 89bio Clinical Study Site
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Glendale, Arizona, United States, 85036
- 89bio Clinical Study Site
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Peoria, Arizona, United States, 85306
- 89bio Clinical Study Site
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Tucson, Arizona, United States, 85712-4044
- 89bio Clinical Study Site
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Tucson, Arizona, United States, 85712-4046
- 89bio Clinical Study Site
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Tucson, Arizona, United States, 85741
- 89bio Clinical Study Site
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Arkansas
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Little Rock, Arkansas, United States, 72205-6414
- 89bio Clinical Study Site
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Little Rock, Arkansas, United States, 72205
- 89bio Clinical Study Site
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California
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Chula Vista, California, United States, 91911
- 89bio Clinical Study Site
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Huntington Park, California, United States, 90255
- 89bio Clinical Study Site
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Long Beach, California, United States, 90808
- 89bio Clinical Study Site
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Orange, California, United States, 92866
- 89bio Clinical Study Site
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Panorama City, California, United States, 91402
- 89bio Clinical Study Site
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Rialto, California, United States, 92377
- 89bio Clinical Study Site
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Santa Ana, California, United States, 92704
- 89bio Clinical Study Site
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Colorado
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Englewood, Colorado, United States, 80113
- 89bio Clinical Study Site
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Florida
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Boynton Beach, Florida, United States, 33472
- 89bio Clinical Study Site
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Bradenton, Florida, United States, 34208
- 89bio Clinical Study Site
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Fort Myers, Florida, United States, 33912
- 89bio Clinical Study Site
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Lakeland, Florida, United States, 33805
- 89bio Clinical Study Site
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Maitland, Florida, United States, 32127
- 89bio Clinical Study Site
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Miami, Florida, United States, 33014
- 89bio Clinical Study Site
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Miami, Florida, United States, 33147
- 89bio Clinical Study Site
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Miami, Florida, United States, 33157
- 89bio Clinical Study Site
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Miami Lakes, Florida, United States, 33016
- 89bio Clinical Study Site
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Ocala, Florida, United States, 34471
- 89bio Clinical Study Site
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Palmetto Bay, Florida, United States, 33157
- 89bio Clinical Study Site
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Pinellas Park, Florida, United States, 33781
- 89bio Clinical Study Site
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Port Orange, Florida, United States, 32127
- 89bio Clinical Study Site
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Sarasota, Florida, United States, 34240
- 89bio Clinical Study Site
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Viera, Florida, United States, 32940
- 89bio Clinical Study Site
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Georgia
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Athens, Georgia, United States, 30607
- 89bio Clinical Study Site
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Sandy Springs, Georgia, United States, 30328
- 89bio Clinical Study Site
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Indiana
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New Albany, Indiana, United States, 47150
- 89bio Clinical Study Site
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South Bend, Indiana, United States, 46635
- 89bio Clinical Study Site
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Iowa
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Iowa City, Iowa, United States, 52246
- 89bio Clinical Study Site
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Kansas
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Topeka, Kansas, United States, 66606
- 89bio Clinical Study Site
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Louisiana
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Marrero, Louisiana, United States, 70072-3151
- 89bio Clinical Study Site
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Marrero, Louisiana, United States, 70072-3155
- 89bio Clinical Study Site
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Monroe, Louisiana, United States, 71201
- 89bio Clinical Study Site
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Shreveport, Louisiana, United States, 71103
- 89bio Clinical Study Site
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Maryland
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Glen Burnie, Maryland, United States, 21061
- 89bio Clinical Study Site
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Greenbelt, Maryland, United States, 20770
- 89bio Clinical Study Site
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Missouri
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St Louis, Missouri, United States, 63033
- 89bio Clinical Study Site
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Nevada
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Las Vegas, Nevada, United States, 89119
- 89bio Clinical Study Site
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Las Vegas, Nevada, United States, 89121
- 89bio Clinical Study Site
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New Jersey
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Florham Park, New Jersey, United States, 07932
- 89bio Clinical Study Site
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New York
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New York, New York, United States, 10033
- 89bio Clinical Study Site
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North Carolina
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Concord, North Carolina, United States, 28027
- 89bio Clinical Study Site
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Ohio
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Columbus, Ohio, United States, 43210
- 89bio Clinical Study Site
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Dayton, Ohio, United States, 45414
- 89bio Clinical Study Site
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Springboro, Ohio, United States, 45066
- 89bio Clinical Study Site
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Westlake, Ohio, United States, 44145
- 89bio Clinical Study Site
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South Carolina
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Greenwood, South Carolina, United States, 29646
- 89bio Clinical Study Site
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Summerville, South Carolina, United States, 29485
- 89bio Clinical Study Site
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Tennessee
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Chattanooga, Tennessee, United States, 37421
- 89bio Clinical Study Site
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Chattanooga, Tennessee, United States, 37411
- 89bio Clinical Study Site
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Hermitage, Tennessee, United States, 37076
- 89bio Clinical Study Site
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Texas
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Austin, Texas, United States, 78757-8051
- 89bio Clinical Study Site
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Austin, Texas, United States, 78757-8059
- 89bio Clinical Study Site
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Beaumont, Texas, United States, 77702
- 89bio Clinical Study Site
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Dallas, Texas, United States, 75234
- 89bio Clinical Study Site
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Dallas, Texas, United States, 75246
- 89bio Clinical Study Site
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Edinburg, Texas, United States, 78539
- 89bio Clinical Study Site
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Fort Worth, Texas, United States, 76104
- 89bio Clinical Study Site
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Garland, Texas, United States, 75044
- 89bio Clinical Study Site
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Houston, Texas, United States, 77030
- 89bio Clinical Study Site
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Houston, Texas, United States, 77099
- 89bio Clinical Study Site
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San Antonio, Texas, United States, 78215
- 89bio Clinical Study Site
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San Antonio, Texas, United States, 78209
- 89bio Clinical Study Site
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San Antonio, Texas, United States, 78229-4801
- 89bio Clinical Study Site
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San Antonio, Texas, United States, 78229-5069
- 89bio Clinical Study Site
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Waco, Texas, United States, 76710
- 89bio Clinical Study Site
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Waco, Texas, United States, 76712
- 89bio Clinical Study Site
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Wichita Falls, Texas, United States, 76301
- 89bio Clinical Study Site
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Utah
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Ogden, Utah, United States, 84405
- 89bio Clinical Study Site
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Sandy City, Utah, United States, 84092
- 89bio Clinical Study Site
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Virginia
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Manassas, Virginia, United States, 20110
- 89bio Clinical Study Site
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Richmond, Virginia, United States, 23235
- 89bio Clinical Study Site
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Richmond, Virginia, United States, 23249
- 89bio Clinical Study Site
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Roanoke, Virginia, United States, 24014
- 89bio Clinical Study Site
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Washington
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Seattle, Washington, United States, 98105
- 89bio Clinical Study Site
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Spokane, Washington, United States, 99202
- 89bio Clinical Study Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Key Inclusion Criteria:
- Age 21 to 75
Biopsy-confirmed NASH with fibrosis stage F2 or F3 per NASH CRN System and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation.
- Qualifying biopsy must be either within 6 months of screening visit or obtained during screening period
Key Exclusion Criteria:
- Have poorly controlled high blood pressure
- Have type 1 diabetes or poorly controlled type 2 diabetes.
- History of cirrhosis or evidence of cirrhosis by clinical, imaging, or liver biopsy evaluation
- Are planning to try to lose weight during the conduct of the study.
- Have a BMI <25 kg/m2
Other inclusion and exclusion criteria may apply.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: BIO89-100 - 15 mg once weekly (QW)
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Subcutaneous injection
Other Names:
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Experimental: BIO89-100 - 30 mg QW
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Subcutaneous injection
Other Names:
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Experimental: BIO89-100 - 44 mg once every 2 weeks (Q2W)
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Subcutaneous injection
Other Names:
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Placebo Comparator: Placebo QW
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Subcutaneous injection
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Placebo Comparator: Placebo Q2W
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Subcutaneous injection
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Experimental: Placebo QW (Main study)/ BIO89-100 - 30 mg QW (Extension)
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Subcutaneous injection
Subcutaneous injection
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis
Time Frame: Week 24
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Nonalcoholic fatty liver disease activity score (NAS) was the sum of the scores of steatosis, inflammation, and ballooning.
NAS score ranged from 0 to 8, with higher scores indicating worse disease severity.
Resolution of NASH was defined as the total absence of ballooning (score=0) and absent or mild inflammation (score=0 to 1).
NASH clinical research system (CRN) fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
Worsening of fibrosis was defined as progression of fibrosis greater than or equal to (≥) 1 stage in NASH CRN fibrosis score.
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Week 24
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Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH
Time Frame: Week 24
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Worsening of NASH was defined as increase in nonalcoholic fatty liver disease activity score (NAS) for ballooning, inflammation, or steatosis.
NAS was the sum of the scores of steatosis, inflammation, and ballooning.
NAS score ranged from 0 to 8, with higher scores indicating worse disease severity.
Fibrosis improvement was defined as ≥1-stage decrease in NASH CRN fibrosis score.
NASH CRN fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
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Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis
Time Frame: Week 24
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NAS was the sum of the scores of steatosis, inflammation, and ballooning.
NAS score ranged from 0 to 8, with higher scores indicating worse disease severity.
Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH CRN fibrosis score.
NASH CRN fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
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Week 24
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Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage
Time Frame: Week 24
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NAS was the sum of the scores of steatosis, inflammation, and ballooning.
NAS score ranged from 0 to 8, with higher scores indicating worse disease severity.
Resolution of NASH was defined as the total absence of ballooning (score=0) and absent or mild inflammation (score=0 to 1).
Fibrosis improvement was defined as ≥1-stage decrease in NASH CRN fibrosis score.
NASH CRN fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
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Week 24
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Main Study: Number of Participants With at Least a 2-point Improvement in NAS Score and Are Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) Responders and Alanine Aminotransferase (ALT) Responders
Time Frame: Week 24
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A responder was defined as achieving ≥2 point improvement in NAS score and are MRI-PDFF responders and ALT responders at Week 24.
NAS was the sum of the scores of steatosis, inflammation, and ballooning.
NAS score ranged from 0 to 8, with higher scores indicating worse disease severity.
MRI-PDFF responder was defined as ≥30% reduction from baseline in liver fat by MRI-PDFF.
ALT responder was defined as ≥17 units/liter (U/L) or ≥30% reduction from baseline in ALT.
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Week 24
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Main Study: Percent Change From Baseline in Serum Triglycerides
Time Frame: Baseline, Week 24
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Baseline, Week 24
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Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c)
Time Frame: Baseline, Week 24
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Baseline, Week 24
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Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c)
Time Frame: Baseline, Week 24
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Baseline, Week 24
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Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c)
Time Frame: Baseline, Week 24
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Baseline, Week 24
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Main Study: Percent Change From Baseline in Adiponectin
Time Frame: Baseline, Week 24
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Baseline, Week 24
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Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin)
Time Frame: Baseline, Week 24
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Baseline, Week 24
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Main Study: Percent Change From Baseline in Alanine Transaminase
Time Frame: Baseline, Week 12 and 24
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Baseline, Week 12 and 24
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Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF)
Time Frame: Baseline, Week 12 and 24
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Baseline, Week 12 and 24
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Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3)
Time Frame: Baseline, Week 12 and 24
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Baseline, Week 12 and 24
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Main Study: Trough Serum Concentration of Pegozafermin
Time Frame: Predose at Week 12 and 24
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Serum trough concentration (ng/mL) of pegozafermin taken from pre-dose samples.
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Predose at Week 12 and 24
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Main and Extension Study: Percent Change From Baseline in Alanine Transaminase
Time Frame: Baseline, Week 48
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Baseline was prior to dosing on Day 1 of the main study.
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Baseline, Week 48
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Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3)
Time Frame: Baseline, Week 48
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Baseline was prior to dosing on Day 1 of the main study.
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Baseline, Week 48
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Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF)
Time Frame: Baseline, Week 48
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Baseline was prior to dosing on Day 1 of the main study.
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Baseline, Week 48
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Main and Extension Study: Trough Serum Concentration of Pegozafermin
Time Frame: Predose at Week 48
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Serum trough concentration (ng/mL) of pegozafermin taken from pre-dose samples.
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Predose at Week 48
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to Week 51
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of IP, whether or not considered related to the IP.
TEAEs were defined as AEs that started or worsened on or after the first dose of study IP up to Week 51.
An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, important medical event or reaction.
A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
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Baseline up to Week 51
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Millie Gottwald, PharmD, 89bio, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Tseng CL, Balic K, Charlton RW, Margalit M, Mansbach H, Savic RM. Population Pharmacokinetics and Pharmacodynamics of Pegozafermin in Patients with Nonalcoholic Steatohepatitis. Clin Pharmacol Ther. 2023 Dec;114(6):1323-1331. doi: 10.1002/cpt.3046. Epub 2023 Oct 2.
- Loomba R, Sanyal AJ, Kowdley KV, Bhatt DL, Alkhouri N, Frias JP, Bedossa P, Harrison SA, Lazas D, Barish R, Gottwald MD, Feng S, Agollah GD, Hartsfield CL, Mansbach H, Margalit M, Abdelmalek MF. Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. N Engl J Med. 2023 Sep 14;389(11):998-1008. doi: 10.1056/NEJMoa2304286. Epub 2023 Jun 24.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 4, 2021
Primary Completion (Actual)
February 14, 2023
Study Completion (Actual)
October 8, 2024
Study Registration Dates
First Submitted
June 10, 2021
First Submitted That Met QC Criteria
June 10, 2021
First Posted (Actual)
June 18, 2021
Study Record Updates
Last Update Posted (Estimated)
January 6, 2026
Last Update Submitted That Met QC Criteria
December 16, 2025
Last Verified
December 1, 2025
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BIO89-100-122
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.