NASH - Nonalcoholic Steatohepatitis
Conditions
Keywords
Liver Diseases, Fatty Liver, Digestive System Diseases, Non-alcoholic Fatty Liver Disease, Metabolic diseases, MASH MAFLD, NASH NAFLD
Brief summary
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.
Interventions
DRUGBIO89-100
Subcutaneous injection
DRUGPlacebo
Subcutaneous injection
Sponsors
89bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis | Week 24 | 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. |
| Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH | Week 24 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage | 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. 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). |
| 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 | Week 24 | 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. |
| Main Study: Percent Change From Baseline in Serum Triglycerides | Baseline, Week 24 | — |
| Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c) | Baseline, Week 24 | — |
| Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c) | Baseline, Week 24 | — |
| Main Study: Percent Change From Baseline in Adiponectin | Baseline, Week 24 | — |
| Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin) | Baseline, Week 24 | — |
| Main Study: Percent Change From Baseline in Alanine Transaminase | Baseline, Week 12 and 24 | — |
| Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c) | Baseline, Week 24 | — |
| Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Baseline, Week 12 and 24 | — |
| Main Study: Trough Serum Concentration of Pegozafermin | Predose at Week 12 and 24 | Serum trough concentration (ng/mL) of pegozafermin taken from pre-dose samples. |
| Main and Extension Study: Percent Change From Baseline in Alanine Transaminase | Baseline, Week 48 | Baseline was prior to dosing on Day 1 of the main study. |
| Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Baseline, Week 48 | Baseline was prior to dosing on Day 1 of the main study. |
| Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Baseline, Week 48 | Baseline was prior to dosing on Day 1 of the main study. |
| Main and Extension Study: Trough Serum Concentration of Pegozafermin | Predose at Week 48 | Serum trough concentration (ng/mL) of pegozafermin taken from pre-dose samples. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to Week 51 | 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. |
| Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Baseline, Week 12 and 24 | — |
| Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis | 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. 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). |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Main and Extension Study: Pegozafermin 15 mg QW Participants received pegozafermin 15 mg QW as a SC injection for 24 weeks in the main study and for 24 weeks in the extension study. | 21 |
| Main and Extension Study: Pegozafermin 30 mg QW Participants received pegozafermin 30 mg QW as a SC injection for 24 weeks in the main study and for 24 weeks in the extension study. | 73 |
| Main and Extension Study: Pegozafermin 44 mg Q2W Participants received pegozafermin 44 mg Q2W as a SC injection for 24 weeks in the main study and for 24 weeks in the extension study. | 57 |
| Main Study: Placebo Pooled Participants received placebo matched to pegozafermin QW or Q2W as a SC injection for 24 weeks in the main study. | 71 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Extension Study (24 Weeks) | Adverse Event | 0 | 2 | 3 | 0 | 0 | 0 |
| Extension Study (24 Weeks) | Lost to Follow-up | 0 | 1 | 1 | 0 | 1 | 0 |
| Extension Study (24 Weeks) | Other than specified | 1 | 0 | 1 | 0 | 1 | 0 |
| Extension Study (24 Weeks) | Withdrawal by Subject | 0 | 0 | 3 | 0 | 2 | 0 |
| Main Study (24 Weeks) | Adverse Event | 1 | 6 | 2 | 1 | 0 | 0 |
| Main Study (24 Weeks) | Lost to Follow-up | 0 | 2 | 0 | 2 | 0 | 0 |
| Main Study (24 Weeks) | Physician Decision | 0 | 2 | 0 | 0 | 0 | 0 |
| Main Study (24 Weeks) | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 |
| Main Study (24 Weeks) | Randomized in error | 0 | 1 | 0 | 2 | 0 | 0 |
| Main Study (24 Weeks) | Withdrawal by Subject | 0 | 3 | 3 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Main and Extension Study: Pegozafermin 15 mg QW | Main and Extension Study: Pegozafermin 30 mg QW | Main and Extension Study: Pegozafermin 44 mg Q2W | Main Study: Placebo Pooled | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 10.45 | 55.3 years STANDARD_DEVIATION 11.15 | 55.2 years STANDARD_DEVIATION 11.23 | 56.3 years STANDARD_DEVIATION 9.01 | 55.6 years STANDARD_DEVIATION 10.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 32 Participants | 20 Participants | 24 Participants | 85 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 41 Participants | 37 Participants | 47 Participants | 137 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 18 Participants | 69 Participants | 54 Participants | 67 Participants | 208 Participants |
| Sex: Female, Male Female | 9 Participants | 50 Participants | 20 Participants | 39 Participants | 118 Participants |
| Sex: Female, Male Male | 12 Participants | 23 Participants | 37 Participants | 32 Participants | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 72 | 0 / 57 | 0 / 50 | 0 / 19 |
| other Total, other adverse events | 21 / 21 | 62 / 72 | 45 / 57 | 41 / 50 | 17 / 19 |
| serious Total, serious adverse events | 1 / 21 | 5 / 72 | 8 / 57 | 6 / 50 | 2 / 19 |
Outcome results
Primary
Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH
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).
Time frame: Week 24
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH | 3 Participants |
| Main Study: Pegozafermin 30 mg QW | Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH | 14 Participants |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH | 11 Participants |
| Main Study: Placebo Pooled | Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH | 4 Participants |
p-value: 0.103995% CI: [-8.71, 37.62]Cochran-Mantel-Haenszel
p-value: 0.008595% CI: [5.24, 32.5]Cochran-Mantel-Haenszel
p-value: 0.007795% CI: [5.26, 35.4]Cochran-Mantel-Haenszel
Primary
Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis
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.
Time frame: Week 24
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis | 5 Participants |
| Main Study: Pegozafermin 30 mg QW | Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis | 12 Participants |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis | 11 Participants |
| Main Study: Placebo Pooled | Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis | 1 Participants |
p-value: <0.000195% CI: [10.04, 59.26]Cochran-Mantel-Haenszel
p-value: 0.000995% CI: [9.05, 32.72]Cochran-Mantel-Haenszel
p-value: 0.000595% CI: [10.04, 37.18]Cochran-Mantel-Haenszel
Secondary
Main and Extension Study: Percent Change From Baseline in Alanine Transaminase
Baseline was prior to dosing on Day 1 of the main study.
Time frame: Baseline, Week 48
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main and Extension Study: Percent Change From Baseline in Alanine Transaminase | -28.51 Percent change | Standard Deviation 37.164 |
| Main Study: Pegozafermin 30 mg QW | Main and Extension Study: Percent Change From Baseline in Alanine Transaminase | -45.08 Percent change | Standard Deviation 25.068 |
| Main Study: Pegozafermin 44 mg Q2W | Main and Extension Study: Percent Change From Baseline in Alanine Transaminase | -38.05 Percent change | Standard Deviation 28.256 |
| Main Study: Placebo Pooled | Main and Extension Study: Percent Change From Baseline in Alanine Transaminase | -5.03 Percent change | Standard Deviation 43.918 |
| Main and Extension Study: Placebo (Main) and Pegozafermin 30 mg QW (Extension) | Main and Extension Study: Percent Change From Baseline in Alanine Transaminase | -31.71 Percent change | Standard Deviation 46.868 |
Secondary
Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF)
Baseline was prior to dosing on Day 1 of the main study.
Time frame: Baseline, Week 48
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | -23.93 Percent Change | Standard Deviation 33.557 |
| Main Study: Pegozafermin 30 mg QW | Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | -48.75 Percent Change | Standard Deviation 29.717 |
| Main Study: Pegozafermin 44 mg Q2W | Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | -25.93 Percent Change | Standard Deviation 50.98 |
| Main Study: Placebo Pooled | Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | -3.15 Percent Change | Standard Deviation 47.992 |
| Main and Extension Study: Placebo (Main) and Pegozafermin 30 mg QW (Extension) | Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | -59.14 Percent Change | Standard Deviation 25.807 |
Secondary
Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3)
Baseline was prior to dosing on Day 1 of the main study.
Time frame: Baseline, Week 48
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | -7.89 Percent Change | Standard Deviation 21.069 |
| Main Study: Pegozafermin 30 mg QW | Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | -16.82 Percent Change | Standard Deviation 23.675 |
| Main Study: Pegozafermin 44 mg Q2W | Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | -14.96 Percent Change | Standard Deviation 21.342 |
| Main Study: Placebo Pooled | Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | 1.64 Percent Change | Standard Deviation 33.082 |
| Main and Extension Study: Placebo (Main) and Pegozafermin 30 mg QW (Extension) | Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | -17.22 Percent Change | Standard Deviation 23.053 |
Secondary
Main and Extension Study: Trough Serum Concentration of Pegozafermin
Serum trough concentration (ng/mL) of pegozafermin taken from pre-dose samples.
Time frame: Predose at Week 48
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main and Extension Study: Trough Serum Concentration of Pegozafermin | 206.54 nanograms/milliliter | Standard Deviation 93.104 |
| Main Study: Pegozafermin 30 mg QW | Main and Extension Study: Trough Serum Concentration of Pegozafermin | 471.28 nanograms/milliliter | Standard Deviation 397.691 |
| Main Study: Pegozafermin 44 mg Q2W | Main and Extension Study: Trough Serum Concentration of Pegozafermin | 111.00 nanograms/milliliter | Standard Deviation 88.644 |
| Main Study: Placebo Pooled | Main and Extension Study: Trough Serum Concentration of Pegozafermin | 553.45 nanograms/milliliter | Standard Deviation 651.882 |
Secondary
Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis
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).
Time frame: Week 24
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis | 5 Participants |
| Main Study: Pegozafermin 30 mg QW | Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis | 34 Participants |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis | 26 Participants |
| Main Study: Placebo Pooled | Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis | 13 Participants |
Secondary
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
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.
Time frame: Week 24
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Pegozafermin 15 mg QW | 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 | 4 Participants |
| Main Study: Pegozafermin 30 mg QW | 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 | 31 Participants |
| Main Study: Pegozafermin 44 mg Q2W | 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 | 22 Participants |
| Main Study: Placebo Pooled | 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 | 5 Participants |
Secondary
Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage
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).
Time frame: Week 24
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage | 2 Participants |
| Main Study: Pegozafermin 30 mg QW | Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage | 7 Participants |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage | 8 Participants |
| Main Study: Placebo Pooled | Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage | 0 Participants |
Secondary
Main Study: Percent Change From Baseline in Adiponectin
Time frame: Baseline, Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in Adiponectin | 22.73 Percent change | Standard Deviation 44.045 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in Adiponectin | 31.36 Percent change | Standard Deviation 49.215 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in Adiponectin | 26.60 Percent change | Standard Deviation 46.353 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in Adiponectin | -6.28 Percent change | Standard Deviation 23.77 |
Secondary
Main Study: Percent Change From Baseline in Alanine Transaminase
Time frame: Baseline, Week 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in Alanine Transaminase | Change at Week 12 | -39.68 Percent change | Standard Deviation 33.615 |
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in Alanine Transaminase | Change at Week 24 | -39.28 Percent change | Standard Deviation 31.478 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in Alanine Transaminase | Change at Week 24 | -42.73 Percent change | Standard Deviation 25.218 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in Alanine Transaminase | Change at Week 12 | -42.04 Percent change | Standard Deviation 23.044 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in Alanine Transaminase | Change at Week 12 | -35.42 Percent change | Standard Deviation 28.874 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in Alanine Transaminase | Change at Week 24 | -31.33 Percent change | Standard Deviation 43.053 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in Alanine Transaminase | Change at Week 12 | -8.62 Percent change | Standard Deviation 35.051 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in Alanine Transaminase | Change at Week 24 | -0.41 Percent change | Standard Deviation 48.798 |
Secondary
Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin)
Time frame: Baseline, Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin) | -2.24 Percent change | Standard Deviation 13.039 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin) | -3.74 Percent change | Standard Deviation 11.216 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin) | -2.00 Percent change | Standard Deviation 11.742 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin) | -0.52 Percent change | Standard Deviation 9.012 |
Secondary
Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF)
Time frame: Baseline, Week 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Change at Week 12 | -45.05 Percent Change | Standard Deviation 25.857 |
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Change at Week 24 | -27.92 Percent Change | Standard Deviation 35.209 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Change at Week 24 | -51.05 Percent Change | Standard Deviation 24.065 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Change at Week 12 | -57.07 Percent Change | Standard Deviation 19.563 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Change at Week 12 | -50.63 Percent Change | Standard Deviation 21.225 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Change at Week 24 | -42.90 Percent Change | Standard Deviation 40.257 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Change at Week 12 | -0.53 Percent Change | Standard Deviation 42.062 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF) | Change at Week 24 | -5.80 Percent Change | Standard Deviation 47.605 |
Secondary
Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c)
Time frame: Baseline, Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c) | 4.69 Percent change | Standard Deviation 13.441 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c) | 15.82 Percent change | Standard Deviation 20.376 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c) | 7.31 Percent change | Standard Deviation 18.69 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c) | -2.01 Percent change | Standard Deviation 13.592 |
Secondary
Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c)
Time frame: Baseline, Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c) | 20.28 Percent change | Standard Deviation 74.84 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c) | -0.42 Percent change | Standard Deviation 35.29 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c) | -5.64 Percent change | Standard Deviation 31.944 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c) | 0.32 Percent change | Standard Deviation 30.811 |
Secondary
Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c)
Time frame: Baseline, Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c) | -3.04 Percent change | Standard Deviation 18.421 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c) | -6.94 Percent change | Standard Deviation 21.26 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c) | -6.95 Percent change | Standard Deviation 24.12 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c) | -0.46 Percent change | Standard Deviation 24.081 |
Secondary
Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3)
Time frame: Baseline, Week 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Change at Week 12 | -35.34 Percent Change | Standard Deviation 26.673 |
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Change at Week 24 | -17.10 Percent Change | Standard Deviation 34.345 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Change at Week 24 | -17.76 Percent Change | Standard Deviation 28.25 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Change at Week 12 | -9.51 Percent Change | Standard Deviation 37.151 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Change at Week 12 | -13.84 Percent Change | Standard Deviation 25.42 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Change at Week 24 | -15.22 Percent Change | Standard Deviation 27.429 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Change at Week 12 | 10.57 Percent Change | Standard Deviation 33.392 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3) | Change at Week 24 | 9.46 Percent Change | Standard Deviation 45.403 |
Secondary
Main Study: Percent Change From Baseline in Serum Triglycerides
Time frame: Baseline, Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Percent Change From Baseline in Serum Triglycerides | -5.79 Percent change | Standard Deviation 19.473 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Percent Change From Baseline in Serum Triglycerides | -14.87 Percent change | Standard Deviation 54.765 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Percent Change From Baseline in Serum Triglycerides | -7.79 Percent change | Standard Deviation 29.612 |
| Main Study: Placebo Pooled | Main Study: Percent Change From Baseline in Serum Triglycerides | 1.02 Percent change | Standard Deviation 31.425 |
Secondary
Main Study: Trough Serum Concentration of Pegozafermin
Serum trough concentration (ng/mL) of pegozafermin taken from pre-dose samples.
Time frame: Predose at Week 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Main Study: Trough Serum Concentration of Pegozafermin | Week 12 | 197.833 nanograms/milliliter | Standard Deviation 110.097 |
| Main Study: Pegozafermin 15 mg QW | Main Study: Trough Serum Concentration of Pegozafermin | Week 24 | 168.127 nanograms/milliliter | Standard Deviation 158.749 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Trough Serum Concentration of Pegozafermin | Week 12 | 534.289 nanograms/milliliter | Standard Deviation 375.149 |
| Main Study: Pegozafermin 30 mg QW | Main Study: Trough Serum Concentration of Pegozafermin | Week 24 | 691.424 nanograms/milliliter | Standard Deviation 718.495 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Trough Serum Concentration of Pegozafermin | Week 24 | 84.033 nanograms/milliliter | Standard Deviation 77.896 |
| Main Study: Pegozafermin 44 mg Q2W | Main Study: Trough Serum Concentration of Pegozafermin | Week 12 | 81.699 nanograms/milliliter | Standard Deviation 77.099 |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: Baseline up to Week 51
Population: Safety analysis set included all randomized participants who received at least 1 dose of IP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study: Pegozafermin 15 mg QW | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 21 Participants |
| Main Study: Pegozafermin 15 mg QW | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Main Study: Pegozafermin 30 mg QW | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 63 Participants |
| Main Study: Pegozafermin 30 mg QW | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 5 Participants |
| Main Study: Pegozafermin 44 mg Q2W | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 46 Participants |
| Main Study: Pegozafermin 44 mg Q2W | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 8 Participants |
| Main Study: Placebo Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 6 Participants |
| Main Study: Placebo Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 42 Participants |
| Main and Extension Study: Placebo (Main) and Pegozafermin 30 mg QW (Extension) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 17 Participants |
| Main and Extension Study: Placebo (Main) and Pegozafermin 30 mg QW (Extension) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |