NASHPhase 1/2NCT04048135

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

A Phase 1/2 study testing Pegozafermin in people with NASH, run by 89bio, Inc. at 26 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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… Read more about this study

Who is it for?: Ages 21 to 75 years
Conditions the study is for: NASH
What is being tested?: Pegozafermin
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 101 participants
Where: 26 sitesin 2 countries
Study dates: 29 Jul 2019to 19 Jan 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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 locations and contacts

26 sites in 2 countries.

Country

City, postcode or hospital

26 sites in 2 countries

United States25 sites

89bio Clinical Study Site
Austin, Texas, 78757
89bio Clinical Study Site
Berlin, New Jersey, 08009
89bio Clinical Study Site
Chandler, Arizona, 85224
89bio Clinical Study Site
Chula Vista, California, 91911
89bio Clinical Study Site
Concord, North Carolina, 28027
89bio Clinical Study Site
East Syracuse, New York, 13057
89bio Clinical Study Site
Edinburg, Texas, 78539
89bio Clinical Study Site
Florham Park, New Jersey, 07932
89bio Clinical Study Site
Greenwood, South Carolina, 29646
89bio Clinical Study Site
Hermitage, Tennessee, 37076
89bio Clinical Study Site
Houston, Texas, 77058
89bio Clinical Study Site
Huntington Beach, California, 92647
89bio Clinical Study Site
Lake Charles, Louisiana, 70601
89bio Clinical Study Site
Madison, Alabama, 35758
89bio Clinical Study Site
Miami, Florida, 33014-3616
89bio Clinical Study Site
Miami Lakes, Florida, 33014
89bio Clinical Study Site
Montclair, California, 91763
89bio Clinical Study Site
Ocala, Florida, 34471
89bio Clinical Study Site
Raleigh, North Carolina, 27612
89bio Clinical Study Site
San Antonio, Texas, 78215
89bio Clinical Study Site
San Antonio, Texas, 78229
89bio Clinical Study Site
Sarasota, Florida, 34240
89bio Clinical Study Site
Summerville, South Carolina, 29485
89bio Clinical Study Site
Tucson, Arizona, 85712
89bio Clinical Study Site
Wichita Falls, Texas, 76301

Other trials in United States

Puerto Rico1 site

89bio Clinical Study Site
San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of BIO89-100 Administered Subcutaneously in Subjects With Nonalcoholic Steatohepatitis (NASH) or With Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH

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).

Conditions: NASH
Being tested: Pegozafermin, Placebo
Keywords: NASH, NAFLD, Liver diseases, Fatty Liver, Metabolic diseases
Medical subject headings: Non-alcoholic Fatty Liver Disease, Liver Diseases, Fatty Liver, Metabolic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PegozaferminDrug
Also called BIO89-100
Subcutaneous injection
PlaceboOther
Subcutaneous injection

Study groups in NCT04048135
Study group	Role	What they receive
Part 1: Pegozafermin 3 milligrams (mg) weekly (QW)	Experimental	Participants were administered 3 mg of pegozafermin QW, via subcutaneous (SC) injection, starting on Day 1 through Day 85. Receives: Drug: Pegozafermin
Part 1: Pegozafermin 9 mg QW	Experimental	Participants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. Receives: Drug: Pegozafermin
Part 1: Pegozafermin 18 mg QW	Experimental	Participants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. Receives: Drug: Pegozafermin
Part 1: Pegozafermin 27 mg QW	Experimental	Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. Receives: Drug: Pegozafermin
Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W)	Experimental	Participants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85. Receives: Drug: Pegozafermin
Part 1: Pegozafermin 36 mg Q2W	Experimental	Participants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85. Receives: Drug: Pegozafermin
Part 1: Placebo QW or Q2W	Placebo comparator	Participants were administered placebo matching to pegozafermin QW or Q2W, via SC injection, starting on Day 1 through Day 85. Receives: Other: Placebo
Part 2: Pegozafermin 27 mg QW	Experimental	Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134. Receives: Drug: Pegozafermin

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: Up to 113 days
Part 2: Number of Participants With TEAEs
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: Up to 162 days
Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin
Measured: Predose and up to 168 hours postdose on Day 29
Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin
Measured: Predose and up to 168 hours postdose on Day 29
Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin
Measured: Predose and up to 168 hours postdose on Day 29
Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin
Measured: Predose and up to 168 hours postdose on Day 29
Part 2: Number of Participants With at Least a 2-point Improvement in NAFLD Activity Score (NAS) With at Least a 1-point Improvement in Ballooning or Lobular Inflammation, and no Worsening of Fibrosis
NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranges from of 0 to 8, with higher scores indicating worse disease severity.
Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH Clinical Research Network (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).
Measured: Day 141

Secondary outcomes (10)

Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin
Number of participants with anti-pegozafermin antibodies (ADA) with status as ADA positive has been reported.
Measured: Up to 113 days
Parts 1 and 2: Percent Change From Baseline in Body Weight
Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM).
Measured: Part 1: Baseline, Day 85; Part 2: Baseline, Day 141
Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3)
LS Mean was calculated using MMRM.
Measured: Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92
LS Mean was calculated using MMRM. HOMA-IR value was calculated by multiplying fasting Glucose (mg/dL) with fasting Insulin (uIU/ml) and then dividing by 405.
Measured: Baseline, Day 92
Part 1: Percent Change From Baseline in Adiponectin at Day 92
LS Mean was calculated using MMRM.
Measured: Baseline, Day 92
Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92
LS Mean was calculated using MMRM.
Measured: Baseline, Day 92
Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50
LS Mean was calculated using MMRM. Adipo-IR was derived from fasting insulin and free fatty acid.
Measured: Baseline, Day 50
Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)
LS Mean was calculated using MMRM.
Measured: Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH
Fibrosis improvement was defined as ≥1-stage decrease in NASH CRN fibrosis score.
Worsening of NASH was defined as increase ≥1 point in NAS for ballooning or inflammation.
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).
Measured: Day 141
Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis
Resolution of NASH included the total absence of ballooning (score=0) and absent or mild inflammation (score 0 to 1).
Worsening of fibrosis was defined as progression of fibrosis ≥1 stage 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).
Measured: Day 141

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Jul 201919 Jan 2022

First posted7 Aug 2019
Study start29 Jul 2019
Primary completion28 Aug 2020
Study completion19 Jan 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for NASHStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 101 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04048135
Sponsor's protocol ID: BIO89-100-002
Status last verified: Feb 2024
First submitted: 4 Aug 2019
Last updated: 2 Apr 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Alkhouri N, Lazas D, Loomba R, Frias JP, Feng S, Tseng L, Balic K, Agollah GD, Kwan T, Iyer JS, Morrow L, Mansbach H, Margalit M, Harrison SA. Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2023 Nov;58(10):1005-1015. doi: 10.1111/apt.17709. Epub 2023 Sep 18.
PubMed 37718721
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.
PubMed 37696614
Loomba R, Lawitz EJ, Frias JP, Ortiz-Lasanta G, Johansson L, Franey BB, Morrow L, Rosenstock M, Hartsfield CL, Chen CY, Tseng L, Charlton RW, Mansbach H, Margalit M. Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):120-132. doi: 10.1016/S2468-1253(22)00347-8. Epub 2022 Dec 12.
PubMed 36521501

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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NASH With Fibrosis, MASH With Fibrosis
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
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Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease

All NASH trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of BIO89-100 Administered Subcutaneously in Subjects With Nonalcoholic Steatohepatitis (NASH) or With Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH
ClinicalTrials.gov ID: NCT04048135
Acronym / sponsor ID: BIO89-100-002
Conditions: NASH
Keywords: NASH, NAFLD, Liver diseases, Fatty Liver, Metabolic diseases
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 101 participants (actual)
Lead sponsor: 89bio, Inc.Industry (pharma, biotech, devices)
Collaborators: ProSciento, Inc.
Study start: 29 Jul 2019 (actual)
Primary completion: 28 Aug 2020 (actual)
Study completion: 19 Jan 2022 (actual)
First posted: 7 Aug 2019 (actual)
Results: Posted 2 Apr 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 8

Arm	Type	Receives
Part 1: Pegozafermin 3 milligrams (mg) weekly (QW)	Experimental	Drug: PegozaferminParticipants were administered 3 mg of pegozafermin QW, via subcutaneous (SC) injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 9 mg QW	Experimental	Drug: PegozaferminParticipants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 18 mg QW	Experimental	Drug: PegozaferminParticipants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 27 mg QW	Experimental	Drug: PegozaferminParticipants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W)	Experimental	Drug: PegozaferminParticipants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 36 mg Q2W	Experimental	Drug: PegozaferminParticipants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.
Part 1: Placebo QW or Q2W	Placebo comparator	Other: PlaceboParticipants were administered placebo matching to pegozafermin QW or Q2W, via SC injection, starting on Day 1 through Day 85.
Part 2: Pegozafermin 27 mg QW	Experimental	Drug: PegozaferminParticipants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134.

Who may qualify

Ages: 21 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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)

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PegozaferminAlso: BIO89-100Subcutaneous injection	Drug	Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W), Part 1: Pegozafermin 18 mg QW, Part 1: Pegozafermin 27 mg QW, Part 1: Pegozafermin 3 milligrams (mg) weekly (QW), Part 1: Pegozafermin 36 mg Q2W, Part 1: Pegozafermin 9 mg QW, Part 2: Pegozafermin 27 mg QW
PlaceboSubcutaneous injection	Other	Part 1: Placebo QW or Q2W

Primary outcome

Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
Time frame: Up to 113 days
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Part 2: Number of Participants With TEAEs
Time frame: Up to 162 days
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin
Time frame: Predose and up to 168 hours postdose on Day 29
Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin
Time frame: Predose and up to 168 hours postdose on Day 29
Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin
Time frame: Predose and up to 168 hours postdose on Day 29
Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin
Time frame: Predose and up to 168 hours postdose on Day 29
Part 2: Number of Participants With at Least a 2-point Improvement in NAFLD Activity Score (NAS) With at Least a 1-point Improvement in Ballooning or Lobular Inflammation, and no Worsening of Fibrosis
Time frame: Day 141
NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranges from of 0 to 8, with higher scores indicating worse disease severity. Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH Clinical Research Network (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).

10 secondary outcomes

Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin
Time frame: Up to 113 days
Parts 1 and 2: Percent Change From Baseline in Body Weight
Time frame: Part 1: Baseline, Day 85; Part 2: Baseline, Day 141
Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3)
Time frame: Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92
Time frame: Baseline, Day 92
Part 1: Percent Change From Baseline in Adiponectin at Day 92
Time frame: Baseline, Day 92
Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92
Time frame: Baseline, Day 92
Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50
Time frame: Baseline, Day 50
Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)
Time frame: Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH
Time frame: Day 141
Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis
Time frame: Day 141

Results and safety

Results posted to the registry on 2 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Pegozafermin 3 Milligrams (mg) Weekly (QW)	6	5
Part 1: Pegozafermin 9 mg QW	12	11
Part 1: Pegozafermin 18 mg QW	11	10
Part 1: Pegozafermin 27 mg QW	10	7
Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W)	14	13
Part 1: Pegozafermin 36 mg Q2W	9	8
Part 1: Placebo QW or Q2W	19	18
Part 2: Pegozafermin 27 mg QW	20	19

Primary outcome: Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs)

Time frame: Up to 113 days. Count of participants. Unit: Participants

Measure	Part 1: Pegozafermin 3 mg QW n = 7	Part 1: Pegozafermin 9 mg QW n = 12	Part 1: Pegozafermin 18 mg QW n = 11	Part 1: Pegozafermin 27 mg QW n = 10	Part 1: Pegozafermin 18 mg Q2W n = 14	Part 1: Pegozafermin 36 mg Q2W n = 9	Part 1: Placebo QW or Q2W n = 18
Value	6	4	7	7	8	8	8

Population analysed: The Safety Analysis set included all randomized participants who received at least 1 dose of study intervention. Arm groups were based upon the actual treatment received for the purpose of safety analysis.

Primary outcome: Part 2: Number of Participants With TEAEs

Time frame: Up to 162 days. Count of participants. Unit: Participants

Measure	Part 2: Pegozafermin 27 mg QW n = 20
Value	18

Population analysed: The Full Analysis Set included all enrolled participants in Part 2 who received at least 1 dose of study intervention.

Primary outcome: Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin

Time frame: Predose and up to 168 hours postdose on Day 29. Median (90% Confidence Interval). Unit: ng/mL

Measure	Part 1: Pegozafermin 3 mg QW n = 6	Part 1: Pegozafermin 9 mg QW n = 12	Part 1: Pegozafermin 18 mg QW n = 11	Part 1: Pegozafermin 27 mg QW n = 10	Part 1: Pegozafermin 18 mg Q2W n = 14	Part 1: Pegozafermin 36 mg Q2W n = 9
Value	103 (59 to 156)	439 (238 to 852)	901 (200 to 1281)	1166 (566 to 2243)	649 (160 to 1300)	1674 (1300 to 2791)

Population analysed: The PK Analysis set included all randomized participants who received at least 1 dose of study intervention and had at least 1 on-study PK measurement.

Primary outcome: Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin

Time frame: Predose and up to 168 hours postdose on Day 29. Median (90% Confidence Interval). Unit: ng*hour/mL

Measure	Part 1: Pegozafermin 3 mg QW n = 6	Part 1: Pegozafermin 9 mg QW n = 12	Part 1: Pegozafermin 18 mg QW n = 11	Part 1: Pegozafermin 27 mg QW n = 10	Part 1: Pegozafermin 18 mg Q2W n = 14	Part 1: Pegozafermin 36 mg Q2W n = 9
Value	11879 (7350 to 17778)	42576 (24394 to 70300)	95765 (24822 to 138904)	112632 (57880 to 231937)	78761 (20520 to 155994)	209436 (153404 to 287414)

Population analysed: The PK Analysis set included all randomized participants who received at least 1 dose of study intervention and had at least 1 on-study PK measurement.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events were collected after dosing to end of study (up to 113 days for Part 1 and up to 162 days for Part 2).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Pegozafermin 3 mg QW	0 of 7 (0%)	6 of 7 (85.7%)	0 of 7
Part 1: Pegozafermin 9 mg QW	0 of 12 (0%)	4 of 12 (33.3%)	0 of 12
Part 1: Pegozafermin 18 mg QW	0 of 11 (0%)	7 of 11 (63.6%)	0 of 11
Part 1: Pegozafermin 27 mg QW	0 of 10 (0%)	7 of 10 (70%)	0 of 10
Part 1: Pegozafermin 18 mg Q2W	1 of 14 (7.1%)	8 of 14 (57.1%)	0 of 14
Part 1: Pegozafermin 36 mg Q2W	1 of 9 (11.1%)	8 of 9 (88.9%)	0 of 9
Part 1: Placebo QW or Q2W	0 of 18 (0%)	8 of 18 (44.4%)	0 of 18
Part 2: Pegozafermin 27 mg QW	0 of 20 (0%)	18 of 20 (90%)	0 of 20

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37718721Alkhouri N, Lazas D, Loomba R, Frias JP, Feng S, Tseng L, Balic K, Agollah GD, Kwan T, Iyer JS, Morrow L, Mansbach H, Margalit M, Harrison SA. Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2023 Nov;58(10):1005-1015. doi: 10.1111/apt.17709. Epub 2023 Sep 18.
Derived from this study: PubMed 37696614Tseng 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.
Derived from this study: PubMed 36521501Loomba R, Lawitz EJ, Frias JP, Ortiz-Lasanta G, Johansson L, Franey BB, Morrow L, Rosenstock M, Hartsfield CL, Chen CY, Tseng L, Charlton RW, Mansbach H, Margalit M. Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):120-132. doi: 10.1016/S2468-1253(22)00347-8. Epub 2022 Dec 12.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Charlton, MD study director

89bio, Inc.

26 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pegozafermin in people with NASH, run by 89bio, Inc. at 26 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) (time frame: Up to 113 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04048135, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024.