NAFLD
Conditions
Brief summary
This study is a phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses of HM15211 in obese subjects with NAFLD
Detailed description
This study will be single-blind and conducted in up to 6 cohorts comprising a total of up to 72 obese subjects with NAFLD. Each cohort will enroll subjects to ensure that at least 12 subjects per cohort will complete the study. Subjects will be randomized to investigational product (IP) or placebo in a 3:1 ratio via an Interactive Web Response System (IWRS). Per cohort (n=12 subjects), 9 subjects will be randomized to IP and 3 subjects to placebo. Cohorts may partially overlap after at least 9 subjects have completed 2-4 weeks of treatment (2 weeks of treatment is reached at Visit week 3) and a dose escalation decision has been made. Study drug will be administered weekly over a period of 12 weeks.
Interventions
DRUGHM15211
A sterile solution of HM15211 contained in pre-filled syringes
A sterile, matching solution in pre-filled syringes
Sponsors
Hanmi Pharmaceutical Company Limited
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index ≥ 30 kg/m2 * Waist circumference ≤ 57 inches * Fasting Plasma Glucose \< 7 mmol/L (126 mg/dL) * HbA1c \< 6.5% * Controlled Attenuation Parameter ≥ 300 dB/m by FibroScan * Liver fat by MRI-PDFF ≥ 10%.
Exclusion criteria
* A history of or active chronic liver disease due to alcohol, auto-immune, HIV, HBV or active HCV-infection or NASH disease * Any history of clinically significant chronic liver disease including esophageal varices, ascites, encephalopathy or any hospitalization for treatment of chronic liver disease; or Model for End Stage Liver Disease (MELD) ≥ 10 * Previous surgical treatment for obesity * Uncontrolled hypertension * Any weight control treatment * History or current diagnosis of acute or chronic pancreatitis or factors for pancreatitis * History of major depression, anxiety, suicidal behavior or attempts, or other psychiatric disorder requiring medical treatment * History or current diagnosis of heart disease * Presence of clinically significant ECG findings * History of renal disease or abnormal kidney function tests * History of alcohol or illicit drug abuse * Daily heavy use of cigarettes or any tobacco product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 12 weeks | Cardiovascular events, rash/inflammatory dermatitis and other skin disorders, GI events, and gallstone formation \[cholelithiasis\] were managed following a separate AE guidance document |
| Incidence of Clinical Renal Function Lab Abnormalities | baseline and 12 weeks | Observed Values and Change from Baseline in Renal Function of Urea Nitrogen |
| Vital Signs | baseline and 12 weeks | Change from baseline in vital signs (Systolic Blood) |
| 12-lead ECG | baseline and 12 weeks | Change from baseline in 12-lead ECG; the primary ECG endpoint was QTcF |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Mass Index | baseline and 12 weeks | Change of Body Mass Index from baseline to 12 weeks after IP injection |
Countries
United States
Participant flow
Recruitment details
Date of first enrollment was November 1st, 2018. Last subject was enrolled on March 3rd, 2020.
Participants by arm
| Arm | Count |
|---|---|
| HM15211 0.01 mg/kg HM15211: A sterile solution of HM15211 contained in pre-filled syringes | 9 |
| HM15211 0.02 mg/kg HM15211: A sterile solution of HM15211 contained in pre-filled syringes | 10 |
| HM15211 0.04 mg/kg HM15211: A sterile solution of HM15211 contained in pre-filled syringes | 12 |
| HM15211 0.06 mg/kg HM15211: A sterile solution of HM15211 contained in pre-filled syringes | 9 |
| HM15211 0.08 mg/kg HM15211: A sterile solution of HM15211 contained in pre-filled syringes | 9 |
| Placebo Placebo of HM15211: A sterile, matching solution in pre-filled syringes | 17 |
| Total | 66 |
Baseline characteristics
| Characteristic | HM15211 0.01 mg/kg | HM15211 0.02 mg/kg | HM15211 0.04 mg/kg | HM15211 0.06 mg/kg | HM15211 0.08 mg/kg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 12 Participants | 9 Participants | 9 Participants | 17 Participants | 66 Participants |
| Race/Ethnicity, Customized Ethnicity : Hispanic or Latino | 7 Participants | 10 Participants | 11 Participants | 8 Participants | 7 Participants | 14 Participants | 57 Participants |
| Race/Ethnicity, Customized Ethnicity : Not Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Race : Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race : Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Race: Multiple | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race : White | 8 Participants | 10 Participants | 10 Participants | 9 Participants | 6 Participants | 15 Participants | 58 Participants |
| Region of Enrollment United States | 9 participants | 10 participants | 12 participants | 9 participants | 9 participants | 17 participants | 66 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 8 Participants | 3 Participants | 3 Participants | 9 Participants | 33 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 8 Participants | 33 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 | 0 / 12 | 0 / 9 | 0 / 9 | 0 / 17 |
| other Total, other adverse events | 7 / 9 | 9 / 10 | 9 / 12 | 8 / 9 | 6 / 9 | 8 / 17 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 | 0 / 12 | 0 / 9 | 0 / 9 | 0 / 17 |
Outcome results
Primary
12-lead ECG
Change from baseline in 12-lead ECG; the primary ECG endpoint was QTcF
Time frame: baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HM15211 0.01 mg/kg | 12-lead ECG | 4.2 milliseconds | Standard Deviation 7.79 |
| HM15211 0.02 mg/kg | 12-lead ECG | 1.3 milliseconds | Standard Deviation 9.51 |
| HM15211 0.04 mg/kg | 12-lead ECG | -1.3 milliseconds | Standard Deviation 7.14 |
| HM15211 0.06 mg/kg | 12-lead ECG | 0 milliseconds | Standard Deviation 3.59 |
| HM15211 0.08 mg/kg | 12-lead ECG | -2.2 milliseconds | Standard Deviation 9.02 |
| Placebo | 12-lead ECG | 2.5 milliseconds | Standard Deviation 4.83 |
Primary
Incidence of Clinical Renal Function Lab Abnormalities
Observed Values and Change from Baseline in Renal Function of Urea Nitrogen
Time frame: baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HM15211 0.01 mg/kg | Incidence of Clinical Renal Function Lab Abnormalities | -1.111 mmol/L | Standard Deviation 0.724 |
| HM15211 0.02 mg/kg | Incidence of Clinical Renal Function Lab Abnormalities | -0.238 mmol/L | Standard Deviation 0.7142 |
| HM15211 0.04 mg/kg | Incidence of Clinical Renal Function Lab Abnormalities | 0.036 mmol/L | Standard Deviation 1.135 |
| HM15211 0.06 mg/kg | Incidence of Clinical Renal Function Lab Abnormalities | -0.754 mmol/L | Standard Deviation 0.7242 |
| HM15211 0.08 mg/kg | Incidence of Clinical Renal Function Lab Abnormalities | -0.893 mmol/L | Standard Deviation 0.5414 |
| Placebo | Incidence of Clinical Renal Function Lab Abnormalities | 0.190 mmol/L | Standard Deviation 1.4962 |
Primary
Number of Participants With Adverse Events
Cardiovascular events, rash/inflammatory dermatitis and other skin disorders, GI events, and gallstone formation \[cholelithiasis\] were managed following a separate AE guidance document
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HM15211 0.01 mg/kg | Number of Participants With Adverse Events | 7 Participants |
| HM15211 0.02 mg/kg | Number of Participants With Adverse Events | 9 Participants |
| HM15211 0.04 mg/kg | Number of Participants With Adverse Events | 9 Participants |
| HM15211 0.06 mg/kg | Number of Participants With Adverse Events | 8 Participants |
| HM15211 0.08 mg/kg | Number of Participants With Adverse Events | 6 Participants |
| Placebo | Number of Participants With Adverse Events | 8 Participants |
Primary
Vital Signs
Change from baseline in vital signs (Systolic Blood)
Time frame: baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HM15211 0.01 mg/kg | Vital Signs | 7.2 mmHg | Standard Deviation 14.96 |
| HM15211 0.02 mg/kg | Vital Signs | 7.1 mmHg | Standard Deviation 12.64 |
| HM15211 0.04 mg/kg | Vital Signs | -0.7 mmHg | Standard Deviation 13.33 |
| HM15211 0.06 mg/kg | Vital Signs | -3.3 mmHg | Standard Deviation 8.67 |
| HM15211 0.08 mg/kg | Vital Signs | -4.5 mmHg | Standard Deviation 18.8 |
| Placebo | Vital Signs | 2.2 mmHg | Standard Deviation 12.27 |
Secondary
Body Mass Index
Change of Body Mass Index from baseline to 12 weeks after IP injection
Time frame: baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HM15211 0.01 mg/kg | Body Mass Index | 35.46 kg/m2 | Standard Deviation 3.835 |
| HM15211 0.02 mg/kg | Body Mass Index | 32.91 kg/m2 | Standard Deviation 2.936 |
| HM15211 0.04 mg/kg | Body Mass Index | 37.86 kg/m2 | Standard Deviation 6.254 |
| HM15211 0.06 mg/kg | Body Mass Index | 40.13 kg/m2 | Standard Deviation 7.113 |
| HM15211 0.08 mg/kg | Body Mass Index | 35.74 kg/m2 | Standard Deviation 3.796 |
| Placebo | Body Mass Index | 34.61 kg/m2 | Standard Deviation 3.521 |