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.

Full analysis set (FAS) included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of investigational product (IP). Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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).

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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).

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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).

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for specified time points.

MRI-PDFF analysis set included all participants in the FAS who had a baseline and at least one follow-up MRI-PDFF assessment. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for specified time points.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for specified time points.

Serum trough concentration (ng/mL) of pegozafermin taken from pre-dose samples.

Pharmacokinetic analysis set included all participants in the FAS who had sufficient data to adequately characterize the trough serum pegozafermin concentrations and had no other events or protocol violations that would adversely affect results, such as not completing the full dose. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for specified time points.

Baseline was prior to dosing on Day 1 of the main study.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Baseline was prior to dosing on Day 1 of the main study.

FAS included all enrolled participants with confirmed fibrosis stage F2 or F3 and NAS ≥4 at baseline per independent review by a 3-pathologist panel who were eligible and assigned a randomization number in the study and received at least 1 dose of IP. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Baseline was prior to dosing on Day 1 of the main study.

MRI-PDFF analysis set included all participants in the FAS who had a baseline and at least one follow-up MRI-PDFF assessment. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Serum trough concentration (ng/mL) of pegozafermin taken from pre-dose samples.

Pharmacokinetic analysis set included all participants in the FAS who had sufficient data to adequately characterize the trough serum pegozafermin concentrations and had no other events or protocol violations that would adversely affect results, such as not completing the full dose. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

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.

Safety analysis set included all randomized participants who received at least 1 dose of IP.