NASH - Nonalcoholic Steatohepatitis
Conditions
Keywords
NASH
Brief summary
This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multiple arm, multicenter study of 3 different doses of HPG1860 versus placebo in subjects with biopsy-confirmed or phenotypic NASH.
Detailed description
This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multiple arm, multicenter study of 3 different doses of HPG1860 versus placebo in subjects with biopsy-confirmed or phenotypic NASH. Screening will occur up to 5 weeks prior to randomization; all eligible subjects will have baseline hepatic imaging during Screening, prior to randomization. Approximately 80 eligible subjects will be randomized 1:1:1:1 on Day 1/Week 0 (T1) to receive either HPG1860 3 mg (n = 20), or 5 mg (n = 20), or 8 mg (n = 20), or placebo (n = 20) for 12 weeks. Following a preplanned interim analysis, a dose cohort may be dropped and/or added.
Interventions
DRUGHPG1860
The dosage form for clinical research is a dry-filled capsule for oral administration manufactured as strengths of 3 mg, 5 mg, and 8 mg.
DRUGPlacebo
Capsule
Sponsors
Hepagene (Shanghai) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
During this study, subjects, investigators, the Sponsor, and the clinical research organization (CRO) (except specific vendors whose role in study conduct requires their unblinding, eg, personnel operationally associated with the interactive response technology \[IRT\]) will be blinded to the study intervention assignment. Study team personnel will remain blinded throughout the study with the exception of a Sponsor Committee who will review interim analysis results and make decisions regarding dropping and/or adding a treatment cohort and an unblinded study team member assigned to monitor that at least 6 subjects in each dose cohort had serial PK measurements taken.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of written informed consent prior to any study-specific procedure. 2. Males and females between 18 and 75 years of age 3. Nonpregnant, nonlactating women. 4. Male subjects must agree to utilize a highly effective method of contraception. 5. Body mass index (BMI) of ≥25 kg/m2 at Screening. 6. Non-cirrhotic NASH subjects. 7. NASH subjects with hepatic fat assessed by a central reader 8. Willing and able to adhere to study restrictions and agree to comply with study protocol.
Exclusion criteria
1. Pregnant or lactating females 2. Current significant alcohol consumption 3. Elevated LDL-C with stable dose of statin an or PCSK9 inhibitor 4. Renal dysfunction or nephritic syndrome or a history of nephritis 5. Recent infarction, unstable angina leading to hospitalization, uncontrolled, symptomatic cardiac arrhythmia 6. Uncontrolled hypertension 7. Type 1 diabetes or uncontrolled T2DM 8. Uncontrolled hypothyroidism 9. Liver transplant and/or other significant liver disease or dysfunction 10. HIV antibody positive 11. Known hypersensitivity or formulation excipient 12. Gastrointestinal conditions or procedures that may affect drug absorption 13. Hematologic or coagulation disorders 14. Unstable weight within the last 3 months 15. Active malignancy 16. Unexplained creatine kinase (CK) \>3 × ULN 17. Blood donation, blood transfusion 18. Unable to undergo or contraindication to MRI procedure 19. A medical or situational finding that in the investigator's opinion may compromise the subject's safety or ability to complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Treatment | 12 weeks | Number of participants Treatment-emergent adverse events (TEAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Liver Fat Content | 12 week | Change from baseline (CFB) in liver fat content (LFC) measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) at Week 12 |
| Percentage of Subjects With ≥30% Reduction in LFC From Baseline | 4 week and 12 week | Percentage of subjects with ≥30% reduction in LFC from baseline measured by MRI-PDFF at Week 4 and Week 12 |
| Change From Baseline (CFB) in Liver Fat Content (LFC) at 4 Week | 4 week | Change from baseline (CFB) in liver fat content (LFC) measured by MRI-PDFF at Week 4 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNaim Alkhouri
Arizona Liver Health - Tucson
Participant flow
Pre-assignment details
Approximately 80 eligible subjects will be randomized 1:1:1:1 to receive either HPG1860 3 mg (n = 20), or 5 mg (n = 20), or 8 mg (n = 20), or placebo (n = 20) for 12 weeks.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54.7 year STANDARD_DEVIATION 10.38 |
| liver fat content | 20.105 liver fat content (%) STANDARD_DEVIATION 4.8983 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 76 Participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 5 / 22 | 9 / 22 | 9 / 21 | 12 / 22 |
| serious Total, serious adverse events | 1 / 22 | 0 / 22 | 0 / 21 | 3 / 22 |
Outcome results
None listed