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Phase Ib/II Study to Evaluate the Efficacy and Safety of GH509 Versus Placebo in Patients With NASH/NAFLD

Primary Purpose

NASH, NAFLD

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
GH509
Placebo
Sponsored by
1Globe Biomedical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NASH

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed written informed consent. ≥ 18 years of age and < 75 years old. BMI ≥ 18 kg/m2. Histologically confirmed NASH (defined as the presence of steatosis, inflammation, and ballooning) within 6 months prior to randomization with stage 2-3 fibrosis according to the NASH Clinical Research Network (CRN) classification OR NAFLD diagnosed by imaging assessment (MRI-PDFF ≥10% within 2 months prior to randomization). ≤ 5% weight change within 6 months prior to randomization. Diagnosed with T2DM. For male or female patient of childbearing potential: Must agree to use contraception or take measures to avoid pregnancy during the study, and for 30 days (female) or 90 days (male) after the last dose of GH509/placebo. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG. Serum alanine transaminase (ALT) and serum aspartate transaminase (AST) ≤ 10×ULN within 14 days prior to randomization. Serum creatinine <1.5×ULN within 14 days prior to randomization. Platelets count ≥ 100,000/mm3 within 14 days prior to randomization. Exclusion Criteria: Subjects with a history of significant alcohol consumption for a period of more than 3 consecutive months any time within 1 year prior to screening. Use of injected or oral antidiabetic agents within 3 months including: Thiazolidinediones; Subcutaneously administered agents; Sodium-glucose co-transporter 2 inhibitors Patients with a history of hypoglycemia within 3 months before study enrollment. Subject uses drugs historically associated with NASH/NAFLD for more than 2 weeks in the year prior to randomization. Treatment with a non-stable dose of statins, fibrates, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in 3 months prior to randomization. LDL ≥190 mg/dL. Treatment with a non-stable dose of drugs with potential anti-NASH/NAFLD effect in the 6 months prior to randomization. Participated in a clinical research study with any investigational product being evaluated for the treatment of diabetes, weight loss, or NASH/NAFLD in the 6 months prior to randomization. Subject is listed for orthotopic liver transplant (OLT) or has medical history of: biliary diversion, organ transplant/bone marrow transplant or undergoing immunosuppressive therapy, hepatocellular, pancreatic, thyroid carcinoma, multiple endocrine neoplasia syndrome type 2 (MEN 2) or other malignant disease. Subject has prior or has planned bariatric surgery. Subject had major surgery within 8 weeks prior to randomization, significant traumatic injury, or anticipation of need for major surgical procedure during the course of the study. Presence of cirrhosis on liver biopsy. Model for End-stage Liver Disease (MELD) score greater than 12. Subject with clinical evidence of hepatic decompensation. Subject has evidence of other forms of chronic liver disease:. Acute cholecystitis or known biliary obstruction. Acute or chronic pancreatitis or administration of total parenteral nutrition within 6 months prior to randomization. Subject has gastrointestinal disorder(s) which would significantly impede the absorption of an oral agent. Subject has concurrent severe infection including diagnoses of fever of unknown origin. Clinically significant and uncontrolled cardiovascular disease within 12 months prior to randomization; cerebrovascular disease, grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication or grade II or greater peripheral vascular disease. Subject with history of human immunodeficiency virus (HIV) infection. Subject with known allergies to the study drug or any of its excipients. Subject with an active, serious medical disease with likely life expectancy of less than 5 years. Subject with active substance abuse, including alcohol and/or inhaled or injection drugs, in the year prior to randomization. Subject has participated in an investigational new drug (IND) trial in the 30 days before randomization. Subject has been previously exposed to GH509. Unable or unwilling to swallow GH509/placebo daily. Ineligibility for MRI. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain. Subject has any other condition which would impede compliance or hinder completion of the study.

Sites / Locations

  • The Affiliated Hospital of Hangzhou Normal UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

GH509

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Determine recommended Phase II dose (RP2D)
Determine the recommended Phase II dose (RP2D) of GH509, which is defined as the dose level that is well tolerated by patients
Change in liver fat content as assessed by MRI-PDFF
Proportion of patients achieving ≥30% hepatic fat reduction (assessed by MRI-PDFF) from baseline after 12 weeks of treatment

Secondary Outcome Measures

Change in liver fat as assessed by MRI-PDFF
Change in percent of hepatic fat fraction assessed by MRI-PDFF from baseline after 12 weeks of treatment.
Proportion of MRI-PDFF responders
Proportion of patients achieving ≥30% hepatic fat reduction assessed by MRI-PDFF from baseline after 12 weeks of treatment
Change in liver enzymes as assessed by serum alanine aminotransferase (ALT)
Change in concentration of serum alanine aminotransferase (ALT) from baseline after 12 weeks of treatment.
Change in glycemic control as assessed by HbA1c
Change in percent of hemoglobin A1c (HbA1c) from baseline after 12 weeks of treatment.
Change in glycemic control as assessed by fasting blood glucose (FBG)
Change in concentration of fasting blood glucose (FBG) from baseline after 12 weeks of treatment.
Change in weight control as assessed by weight loss
Change in body weight from baseline after 12 weeks of treatment.
Tolerability and safety as assessed by incidence of adverse events
Number and percentage of adverse events and serious adverse events.

Full Information

First Posted
February 24, 2023
Last Updated
March 26, 2023
Sponsor
1Globe Biomedical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05784779
Brief Title
Phase Ib/II Study to Evaluate the Efficacy and Safety of GH509 Versus Placebo in Patients With NASH/NAFLD
Official Title
Phase Ib/II Study to Evaluate the Efficacy and Safety of GH509 Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH)/Non-alcoholic Fatty Liver Disease (NAFLD)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 28, 2023 (Actual)
Primary Completion Date
May 28, 2024 (Anticipated)
Study Completion Date
June 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
1Globe Biomedical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a Phase Ib/II, randomized, double-blind, placebo-controlled, international multi-center clinical study to investigate the efficacy and safety of GH509 in subjects with NASH/NAFLD

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NASH, NAFLD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GH509
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
GH509
Intervention Description
Orally, once daily before bedtime (qhs)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Orally, once daily before bedtime (qhs)
Primary Outcome Measure Information:
Title
Determine recommended Phase II dose (RP2D)
Description
Determine the recommended Phase II dose (RP2D) of GH509, which is defined as the dose level that is well tolerated by patients
Time Frame
12 weeks
Title
Change in liver fat content as assessed by MRI-PDFF
Description
Proportion of patients achieving ≥30% hepatic fat reduction (assessed by MRI-PDFF) from baseline after 12 weeks of treatment
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Change in liver fat as assessed by MRI-PDFF
Description
Change in percent of hepatic fat fraction assessed by MRI-PDFF from baseline after 12 weeks of treatment.
Time Frame
12 weeks
Title
Proportion of MRI-PDFF responders
Description
Proportion of patients achieving ≥30% hepatic fat reduction assessed by MRI-PDFF from baseline after 12 weeks of treatment
Time Frame
12 weeks
Title
Change in liver enzymes as assessed by serum alanine aminotransferase (ALT)
Description
Change in concentration of serum alanine aminotransferase (ALT) from baseline after 12 weeks of treatment.
Time Frame
12 weeks
Title
Change in glycemic control as assessed by HbA1c
Description
Change in percent of hemoglobin A1c (HbA1c) from baseline after 12 weeks of treatment.
Time Frame
12 weeks
Title
Change in glycemic control as assessed by fasting blood glucose (FBG)
Description
Change in concentration of fasting blood glucose (FBG) from baseline after 12 weeks of treatment.
Time Frame
12 weeks
Title
Change in weight control as assessed by weight loss
Description
Change in body weight from baseline after 12 weeks of treatment.
Time Frame
12 weeks
Title
Tolerability and safety as assessed by incidence of adverse events
Description
Number and percentage of adverse events and serious adverse events.
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed written informed consent. ≥ 18 years of age and < 75 years old. BMI ≥ 18 kg/m2. Histologically confirmed NASH (defined as the presence of steatosis, inflammation, and ballooning) within 6 months prior to randomization with stage 2-3 fibrosis according to the NASH Clinical Research Network (CRN) classification OR NAFLD diagnosed by imaging assessment (MRI-PDFF ≥10% within 2 months prior to randomization). ≤ 5% weight change within 6 months prior to randomization. Diagnosed with T2DM. For male or female patient of childbearing potential: Must agree to use contraception or take measures to avoid pregnancy during the study, and for 30 days (female) or 90 days (male) after the last dose of GH509/placebo. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG. Serum alanine transaminase (ALT) and serum aspartate transaminase (AST) ≤ 10×ULN within 14 days prior to randomization. Serum creatinine <1.5×ULN within 14 days prior to randomization. Platelets count ≥ 100,000/mm3 within 14 days prior to randomization. Exclusion Criteria: Subjects with a history of significant alcohol consumption for a period of more than 3 consecutive months any time within 1 year prior to screening. Use of injected or oral antidiabetic agents within 3 months including: Thiazolidinediones; Subcutaneously administered agents; Sodium-glucose co-transporter 2 inhibitors Patients with a history of hypoglycemia within 3 months before study enrollment. Subject uses drugs historically associated with NASH/NAFLD for more than 2 weeks in the year prior to randomization. Treatment with a non-stable dose of statins, fibrates, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in 3 months prior to randomization. LDL ≥190 mg/dL. Treatment with a non-stable dose of drugs with potential anti-NASH/NAFLD effect in the 6 months prior to randomization. Participated in a clinical research study with any investigational product being evaluated for the treatment of diabetes, weight loss, or NASH/NAFLD in the 6 months prior to randomization. Subject is listed for orthotopic liver transplant (OLT) or has medical history of: biliary diversion, organ transplant/bone marrow transplant or undergoing immunosuppressive therapy, hepatocellular, pancreatic, thyroid carcinoma, multiple endocrine neoplasia syndrome type 2 (MEN 2) or other malignant disease. Subject has prior or has planned bariatric surgery. Subject had major surgery within 8 weeks prior to randomization, significant traumatic injury, or anticipation of need for major surgical procedure during the course of the study. Presence of cirrhosis on liver biopsy. Model for End-stage Liver Disease (MELD) score greater than 12. Subject with clinical evidence of hepatic decompensation. Subject has evidence of other forms of chronic liver disease:. Acute cholecystitis or known biliary obstruction. Acute or chronic pancreatitis or administration of total parenteral nutrition within 6 months prior to randomization. Subject has gastrointestinal disorder(s) which would significantly impede the absorption of an oral agent. Subject has concurrent severe infection including diagnoses of fever of unknown origin. Clinically significant and uncontrolled cardiovascular disease within 12 months prior to randomization; cerebrovascular disease, grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication or grade II or greater peripheral vascular disease. Subject with history of human immunodeficiency virus (HIV) infection. Subject with known allergies to the study drug or any of its excipients. Subject with an active, serious medical disease with likely life expectancy of less than 5 years. Subject with active substance abuse, including alcohol and/or inhaled or injection drugs, in the year prior to randomization. Subject has participated in an investigational new drug (IND) trial in the 30 days before randomization. Subject has been previously exposed to GH509. Unable or unwilling to swallow GH509/placebo daily. Ineligibility for MRI. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain. Subject has any other condition which would impede compliance or hinder completion of the study.
Facility Information:
Facility Name
The Affiliated Hospital of Hangzhou Normal University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310015
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Baiyun Zhao
Phone
0571-88358070
Email
2026609969@qq.com

12. IPD Sharing Statement

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Phase Ib/II Study to Evaluate the Efficacy and Safety of GH509 Versus Placebo in Patients With NASH/NAFLD

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