Nonalcoholic Steatohepatitis (NASH)
Conditions
Keywords
NASH, PRO 140, Leronlimab
Brief summary
This is a phase II study of of Leronlimab (PRO 140)-Humanized monoclonal antibody to CCR5 in patients with Nonalcoholic Steatohepatitis (NASH).
Detailed description
This is an exploratory phase II, multi-center, two-part study (Part 1: randomized, placebo-controlled, two-arm with 60 patients; Part 2: non-randomized, single-arm, open-label with 30 patients) designed to evaluate the safety and efficacy of leronlimab after subcutaneous (SC) administration in patients with NASH for 13 weeks. A Follow Up visit was conducted 28 (± 3) days after receiving the last study treatment (i.e., after last dose of Leronlimab (PRO 140) or placebo.
Interventions
DRUGPlacebo
Placebo will be administered subcutaneously every week for 13 weeks.
DRUGleronlimab 700 mg
700 mg leronlimab will be administered subcutaneously every week for 13 weeks.
DRUGleronlimab 350 mg
350 mg leronlimab will be administered subcutaneously every week for 13 weeks.
Sponsors
CytoDyn, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Subjects are required to meet ALL of the following criteria for enrollment into the study: 1. Subject is a male or female between 18 to 75 years of age inclusive. 2. Evidence of nonalcoholic steatohepatitis (NASH) based on one of the following criteria: * Criteria 1: Histologically-confirmed diagnosis of NASH on a liver biopsy, or * Criteria 2: FibroScan or Shearwave US during screening (or within 6 months before screening) shows kPa ≥7 but \<14 and CAP ≥260. 3. Subject shows presence of hepatic fat fraction as defined by ≥ 8% on MRI-PDFF and cT1 ≥ 800 ms at Screening. 4. Has had a stable body weight (±5%) within 6 months prior to Screening. 5. Body Mass Index (BMI) ≥ 28 kg/m2 at Screening 6. Has clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator. 7. Laboratory Screening results as indicated below: 1. AST:ALT Ratio ≤ 1, if AST or ALT value is \> ULN 2. Screening Liver enzymes (AST, ALT, and ALK PHOS) \< 5 x ULN. 3. Total Bilirubin ≤ 1.3 mg/dL (except if Gilbert's Disease) 4. Platelet count ≥ 150,000/mm3 5. International normalized ratio (INR) \< 1.3 6. Estimated Glomerular Filtration Rate (eGFR) ≥ 60/mL/min 7. Glycosylated hemoglobin (HbA1c) \< 9%. 8. Thyroid-Stimulating Hormone (TSH) within normal reference range. Note: Any subject with a non-clinically significant TSH value outside of the normal range may be enrolled if their T3 and free T4 values are within the normal range. 8. Subjects with pre-diabetes or type 2 diabetes will be allowed to participate if the following criteria is met: * Subjects who are taking anti-diabetic medications should be on a stable dose for a period of at least 3 months prior to Screening and do not anticipate clinically significant dose adjustments during the course of study. * Subjects must be on a stable diet/lifestyle regimen for at least 3 months prior to screening and do not anticipate a clinically significant change during the course of study. 9. Subjects who are taking Vitamin E should be on a stable dose of Vitamin E (if ≥ 400 IU) for a period of at least 4 weeks prior to Screening and do not anticipate dose adjustments for the duration of the study. 10. Both male and female patients and their partners of childbearing potential must agree to use two medically accepted methods of contraception (e.g., barrier contraceptives \[male condom, female condom, or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings\], or one of the following methods of birth control (intrauterine devices, tubal sterilization or vasectomy) or must practice complete abstinence from intercourse of reproductive potential from study entry to 6 months after the last day of treatment (excluding women who are not of childbearing potential and men who have been sterilized). 11. Females of child-bearing potential must have a negative serum pregnancy test at Screening Visit and negative urine pregnancy test prior to receiving the first dose of study drug; and Male participants must agree to use contraception and refrain from donating sperm for at least 90 days after the last dose of study intervention. 12. Subject is willing and able to give informed consent prior to any study specific procedures being performed. 13. Subject is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures and study restrictions
Exclusion criteria
Subjects meeting ANY of the following criteria will be excluded from enrollment: 1. Any concurrent clinically significant liver disease with an etiology other than NASH including autoimmune hepatitis, alcoholic hepatitis, hypoxic/ischemic hepatopathy, and biliary tract disease. 2. History of alcohol consumption greater than 21/units/week (for males) and 14/units/week (for females) within the last 2 years prior to screening. Note: Use of online unit calculator for alcohol consumption is recommended (e.g., https://alcoholchange.org.uk/alcohol-facts/interactive-tools/unit-calculator) 3. Any drug-induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis. 4. Undergone major surgery, including liver surgery, within 6 months prior to screening deemed clinically significant by the investigator. 5. Prior or pending liver transplantation. 6. History or presence of cirrhosis or stage 4 fibrosis in historical liver biopsy and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding. 7. Active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test), hepatitis C (defined as having a positive Anti-HCV test with detectable reflex HCV RNA; Note: Subject with positive Anti-HCV test and with undetectable HCV RNA would not be excluded), acute hepatitis A (defined as subjects with serum positive for hepatitis A IgM (HAV) antibody) or acute hepatitis E (defined as having anti-HEV IgM antibody). 8. Any active infection requiring systemic therapy at the time of screening, which is considered clinically significant per the Investigator. 9. Positive test for human immunodeficiency virus (HIV) or HIV infection. 10. History of bleeding diathesis within 6 months of screening. 11. Any malignancy within the past 5 years, excluding successfully treated basal cell carcinoma or squamous cell carcinoma without evidence of metastases. 12. Seizure disorder requiring ongoing antiseizure therapy or with any condition that, in the judgment of the investigator, is likely to increase the risk of seizure (e.g. CNS malignancy) 13. Clinically significant active cardiac disease which would interfere with study conduct or study results interpretation per the PI. 14. Any known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 15. Prior therapy with Leronlimab or any other CCR5 antagonist (e.g. maraviroc) within 6 months prior to screening. 16. History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized monoclonal antibodies. 17. Any condition requiring continuous systemic treatment with immunosuppressive (such as corticosteroids) or immunomodulatory medications. Note: Inhaled or topical steroids of up to 5 mg daily prednisone equivalent dose are permitted in the bsence of active autoimmune disease. 18. History of administration of a live, attenuated vaccine within four weeks prior to start of PRO 140 treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed. However intranasal influenza vaccines (e.g., Flu-Mist ®) are live attenuated vaccines, and are not allowed. 19. Currently participating in an investigational study or received an investigational drug within 28 days or 5 half-lives (whichever is longer) prior to study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI-PDFF Change From Baseline to Week 14 | Change from baseline (day one, first day of treatment) to EOT (day 92, 13 weeks of treatment) | Change in hepatic fat fraction from baseline assessed by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) at week 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alkaline Phosphatase | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Alkaline Phosphatase |
| Alanine Aminotraferase (ALT) | Measured at baseline (day 1) and at day 92 | Change from Baseline to Week 14 in Alanine Aminotraferase (ALT) |
| Aspartate Aminotransferase (AST) | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Aspartate Aminotransferase (AST) |
| GGT S | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Gamma Glutamyl transferase, GGT S |
| Neutrophils/Leukocytes | Measured at baseline (day 1, start of treatment) and at EOT (day 92) | Change in Neutrophils/Leukocytes ratio from Baseline to Week 14 |
| CCL2 | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Monocyte Chemotactic Protein 1 (CCL2) |
| CCL3 | Measured at baseline (day 1, start of treatment) and at EOT (day 92) | Change from Baseline (day 1, start of treatment) to Week 14 (EOT) in Macrophage Inflammatory Protein 1 Alpha |
| CCL5 (Rantes) | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in CCL-5 (Rantes) |
| Fibro Test Score | Measured at baseline (day 1, start of treatment) and at EOT (day 92) | Change from baseline (day 1, start of treatment) to Week 14 (EOT) in Fibro Test Score measured on a scale of 0 to 1, where 0 to 0.27 is no fibrosis, 0.27 to 0.48 is minimal fibrosis, 0.48 to 0.58 is moderate fibrosis, 0.58 to 0.74 is advanced fibrosis and 0.74 to 1.00 is severe fibrosis (Cirrhosis). Minimum score is zero, maximum score (worst outcome) is 1. |
| MRI-cT1 Change From Baseline to Week 14 | Measured at baseline (day 1) and at EOT (day 92) | MRI corrected T1 (cT1) is emerging as a promising quantitative surrogate metric for assessing a composite of liver inflammation and fibrosis. |
| CCL18 | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to week 14 in CCL18 (Pulmonary & Activation-Reg Chemokine) |
| VCAM | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Vascular Cell Adhesion Molecule 1 |
| Interleukin-1 Beta | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Interleukin-1 Beta |
| IL-1RA | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Interleukin 1 Receptor Antagonist |
| IL-6 | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Interleukin 6 |
| IL-8 | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline to Week 14 in Interleukin 8 |
| TNF Receptor 2 | Measured at baseline (day 1, start of treatment) and at EOT (day 92) | Change from baseline (day 1, start of treatment) to Week 14 (EOT) in Tumor Necrosis Factor Receptor 2 |
| TIMP-1 | Measured at baseline (day 1) and at EOT (day 92) | Change from Baseline (day 1, start of treatment) to Week 14 (EOT) in Tissue Inhibitor of Metalloproteinases 1 (ng/mL) |
| En Rage | Measured at baseline (day 1) and at EOT (day 92) | Change from baseline (start of treatment, day 1) to Week 14 (EOT) in En Rage (Receptor Advanced Glycation End-Products) |
| CCL11( Eotaxin-1) | Measured at baseline (day 1, start of treatment) and at EOT (day 92) | Change from Baseline to Week 14 in Eosinophils Chemotactic Protein |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Leronlimab 700 mg 700mg SC weekly injection | 30 |
| Leronlimab 350 mg 350mg SC weekly injection | 27 |
| Placebo Placebo SC weekly injection | 30 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 |
| Overall Study | Sponsor Wish | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 2 |
| Overall Study | Withdrawal of Consent | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Leronlimab 700 mg | Leronlimab 350 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous Age | 53.2 years STANDARD_DEVIATION 13.68 | 52.4 years STANDARD_DEVIATION 8.38 | 55.6 years STANDARD_DEVIATION 10.47 | 53.80 years STANDARD_DEVIATION 11.1 |
| BMI | 41.2 kg/m^2 STANDARD_DEVIATION 9.56 | 38.0 kg/m^2 STANDARD_DEVIATION 5.52 | 38.4 kg/m^2 STANDARD_DEVIATION 5.89 | 39.2 kg/m^2 STANDARD_DEVIATION 7.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 16 Participants | 12 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 11 Participants | 18 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 22 Participants | 28 Participants | 80 Participants |
| Sex: Female, Male Female | 19 Participants | 13 Participants | 9 Participants | 41 Participants |
| Sex: Female, Male Male | 11 Participants | 14 Participants | 21 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 1 / 27 | 0 / 30 |
| other Total, other adverse events | 28 / 30 | 21 / 27 | 21 / 30 |
| serious Total, serious adverse events | 2 / 30 | 1 / 27 | 2 / 30 |
Outcome results
Primary
MRI-PDFF Change From Baseline to Week 14
Change in hepatic fat fraction from baseline assessed by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) at week 14
Time frame: Change from baseline (day one, first day of treatment) to EOT (day 92, 13 weeks of treatment)
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leronlimab 700 mg | MRI-PDFF Change From Baseline to Week 14 | -1.25 Percentage of hepatic fat fraction |
| Leronlimab 350 mg | MRI-PDFF Change From Baseline to Week 14 | -0.90 Percentage of hepatic fat fraction |
| Placebo | MRI-PDFF Change From Baseline to Week 14 | 0.90 Percentage of hepatic fat fraction |
Secondary
Alanine Aminotraferase (ALT)
Change from Baseline to Week 14 in Alanine Aminotraferase (ALT)
Time frame: Measured at baseline (day 1) and at day 92
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | Alanine Aminotraferase (ALT) | 4.77 U/L | Standard Deviation 32.06 |
| Leronlimab 350 mg | Alanine Aminotraferase (ALT) | -0.76 U/L | Standard Deviation 16.65 |
| Placebo | Alanine Aminotraferase (ALT) | 1.79 U/L | Standard Deviation 18.83 |
Secondary
Alkaline Phosphatase
Change from Baseline to Week 14 in Alkaline Phosphatase
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | Alkaline Phosphatase | 0.37 IU/L | Standard Deviation 7.77 |
| Leronlimab 350 mg | Alkaline Phosphatase | -3.68 IU/L | Standard Deviation 7.99 |
| Placebo | Alkaline Phosphatase | -0.83 IU/L | Standard Deviation 7.75 |
Secondary
Aspartate Aminotransferase (AST)
Change from Baseline to Week 14 in Aspartate Aminotransferase (AST)
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | Aspartate Aminotransferase (AST) | 1.40 U/L | Standard Deviation 15.1 |
| Leronlimab 350 mg | Aspartate Aminotransferase (AST) | -6.12 U/L | Standard Deviation 33.33 |
| Placebo | Aspartate Aminotransferase (AST) | 2.17 U/L | Standard Deviation 13.23 |
Secondary
CCL11( Eotaxin-1)
Change from Baseline to Week 14 in Eosinophils Chemotactic Protein
Time frame: Measured at baseline (day 1, start of treatment) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | CCL11( Eotaxin-1) | 29.30 pg/mL | Standard Deviation 87.67 |
| Leronlimab 350 mg | CCL11( Eotaxin-1) | -3.88 pg/mL | Standard Deviation 95.1 |
| Placebo | CCL11( Eotaxin-1) | -41.32 pg/mL | Standard Deviation 116.25 |
Secondary
CCL18
Change from Baseline to week 14 in CCL18 (Pulmonary & Activation-Reg Chemokine)
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | CCL18 | 6.77 ng/mL | Standard Deviation 36.16 |
| Leronlimab 350 mg | CCL18 | -27.28 ng/mL | Standard Deviation 40.49 |
| Placebo | CCL18 | -2.14 ng/mL | Standard Deviation 34.43 |
Secondary
CCL2
Change from Baseline to Week 14 in Monocyte Chemotactic Protein 1 (CCL2)
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | CCL2 | 57.60 pg/mL | Standard Deviation 175.98 |
| Leronlimab 350 mg | CCL2 | -77.0 pg/mL | Standard Deviation 161.99 |
| Placebo | CCL2 | -38.57 pg/mL | Standard Deviation 140.75 |
Secondary
CCL3
Change from Baseline (day 1, start of treatment) to Week 14 (EOT) in Macrophage Inflammatory Protein 1 Alpha
Time frame: Measured at baseline (day 1, start of treatment) and at EOT (day 92)
Population: Safety Analysis Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | CCL3 | 1.40 pg/mL | Standard Deviation 6.22 |
| Leronlimab 350 mg | CCL3 | -7.20 pg/mL | Standard Deviation 5.03 |
| Placebo | CCL3 | -0.96 pg/mL | Standard Deviation 2.62 |
Secondary
CCL5 (Rantes)
Change from Baseline to Week 14 in CCL-5 (Rantes)
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | CCL5 (Rantes) | 8.14 ng/mL | Standard Deviation 15.82 |
| Leronlimab 350 mg | CCL5 (Rantes) | -6.80 ng/mL | Standard Deviation 44.4 |
| Placebo | CCL5 (Rantes) | -0.39 ng/mL | Standard Deviation 8.28 |
Secondary
En Rage
Change from baseline (start of treatment, day 1) to Week 14 (EOT) in En Rage (Receptor Advanced Glycation End-Products)
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | En Rage | 30.77 ng/mL | Standard Deviation 229.87 |
| Leronlimab 350 mg | En Rage | -60.40 ng/mL | Standard Deviation 245.32 |
| Placebo | En Rage | 54.96 ng/mL | Standard Deviation 141.75 |
Secondary
Fibro Test Score
Change from baseline (day 1, start of treatment) to Week 14 (EOT) in Fibro Test Score measured on a scale of 0 to 1, where 0 to 0.27 is no fibrosis, 0.27 to 0.48 is minimal fibrosis, 0.48 to 0.58 is moderate fibrosis, 0.58 to 0.74 is advanced fibrosis and 0.74 to 1.00 is severe fibrosis (Cirrhosis). Minimum score is zero, maximum score (worst outcome) is 1.
Time frame: Measured at baseline (day 1, start of treatment) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | Fibro Test Score | 0.02 score on a scale | Standard Deviation 0.06 |
| Leronlimab 350 mg | Fibro Test Score | 0.01 score on a scale | Standard Deviation 0.07 |
| Placebo | Fibro Test Score | -0.00 score on a scale | Standard Deviation 0.06 |
Secondary
GGT S
Change from Baseline to Week 14 in Gamma Glutamyl transferase, GGT S
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | GGT S | 5.67 U/L | Standard Deviation 14.12 |
| Leronlimab 350 mg | GGT S | -3.00 U/L | Standard Deviation 14.73 |
| Placebo | GGT S | 0.90 U/L | Standard Deviation 11.61 |
Secondary
IL-1RA
Change from Baseline to Week 14 in Interleukin 1 Receptor Antagonist
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | IL-1RA | 6.37 pg/mL | Standard Deviation 125.39 |
| Leronlimab 350 mg | IL-1RA | -16.24 pg/mL | Standard Deviation 74.4 |
| Placebo | IL-1RA | 15.93 pg/mL | Standard Deviation 54.63 |
Secondary
IL-6
Change from Baseline to Week 14 in Interleukin 6
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | IL-6 | 0.17 pg/mL | Standard Deviation 1.18 |
| Leronlimab 350 mg | IL-6 | -0.24 pg/mL | Standard Deviation 0.68 |
| Placebo | IL-6 | 0.31 pg/mL | Standard Deviation 1.74 |
Secondary
IL-8
Change from Baseline to Week 14 in Interleukin 8
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | IL-8 | -3.25 pg/mL | Standard Deviation 8.89 |
| Leronlimab 350 mg | IL-8 | -2.18 pg/mL | Standard Deviation 7.81 |
| Placebo | IL-8 | -0.54 pg/mL | Standard Deviation 5 |
Secondary
Interleukin-1 Beta
Change from Baseline to Week 14 in Interleukin-1 Beta
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | Interleukin-1 Beta | 0.06 pg/mL | Standard Deviation 0.31 |
| Leronlimab 350 mg | Interleukin-1 Beta | 0.09 pg/mL | Standard Deviation 0.46 |
| Placebo | Interleukin-1 Beta | 0.16 pg/mL | Standard Deviation 0.61 |
Secondary
MRI-cT1 Change From Baseline to Week 14
MRI corrected T1 (cT1) is emerging as a promising quantitative surrogate metric for assessing a composite of liver inflammation and fibrosis.
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leronlimab 700 mg | MRI-cT1 Change From Baseline to Week 14 | -7.0 Milliseconds (ms) |
| Leronlimab 350 mg | MRI-cT1 Change From Baseline to Week 14 | -2.00 Milliseconds (ms) |
| Placebo | MRI-cT1 Change From Baseline to Week 14 | 22.0 Milliseconds (ms) |
Secondary
Neutrophils/Leukocytes
Change in Neutrophils/Leukocytes ratio from Baseline to Week 14
Time frame: Measured at baseline (day 1, start of treatment) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | Neutrophils/Leukocytes | 0.93 Ratio of neutrophils to leukocytes | Standard Deviation 5.94 |
| Leronlimab 350 mg | Neutrophils/Leukocytes | -4.32 Ratio of neutrophils to leukocytes | Standard Deviation 8.42 |
| Placebo | Neutrophils/Leukocytes | 0.55 Ratio of neutrophils to leukocytes | Standard Deviation 6.07 |
Secondary
TIMP-1
Change from Baseline (day 1, start of treatment) to Week 14 (EOT) in Tissue Inhibitor of Metalloproteinases 1 (ng/mL)
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | TIMP-1 | 8.30 ng/mL | Standard Deviation 32.39 |
| Leronlimab 350 mg | TIMP-1 | -11.76 ng/mL | Standard Deviation 29.33 |
| Placebo | TIMP-1 | 1.25 ng/mL | Standard Deviation 25.62 |
Secondary
TNF Receptor 2
Change from baseline (day 1, start of treatment) to Week 14 (EOT) in Tumor Necrosis Factor Receptor 2
Time frame: Measured at baseline (day 1, start of treatment) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | TNF Receptor 2 | 1.04 pg/mL | Standard Deviation 3.25 |
| Leronlimab 350 mg | TNF Receptor 2 | -1.66 pg/mL | Standard Deviation 2.24 |
| Placebo | TNF Receptor 2 | 0.79 pg/mL | Standard Deviation 1.72 |
Secondary
VCAM
Change from Baseline to Week 14 in Vascular Cell Adhesion Molecule 1
Time frame: Measured at baseline (day 1) and at EOT (day 92)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leronlimab 700 mg | VCAM | 35.93 ng/mL | Standard Deviation 178.64 |
| Leronlimab 350 mg | VCAM | -82.80 ng/mL | Standard Deviation 79.95 |
| Placebo | VCAM | 8.89 ng/mL | Standard Deviation 109.96 |