Clinical trial NCT04607655: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered GB1211 in Participants With Suspected or Confirmed Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis
Official title: GULLIVER-1 - A Randomised, Double-Blind, Placebo Controlled, Phase Ib, 12-week Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered GB1211 in Participants With Suspected or Confirmed Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Non-alcoholic Steatohepatitis (NASH)
Keywords: GB1211
Non-alcoholic Steatohepatitis
NASH
Liver Fibrosis
Galectin-3 Inhibitor
Lead sponsor: Galecto Biotech AB
Sponsor class: INDUSTRY
Collaborators: name: Covance
First posted: 2020-10-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All subjects eligible for the study will be randomised into one of the three treatment arms:

A. GB1211 100 mg twice a day B. GB1211 10 mg twice a day C. Placebo twice a day
Primary purpose: TREATMENT

Brief summary: This study is a randomised, double-blind, placebo controlled, phase Ib trial in subjects with suspected or confirmed non-alcoholic steatohepatitis (NASH) and liver fibrosis

Detailed description: This study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered GB1211 a gelectin-3 inhibitor over 12 weeks. Participants will receive two doses of GB1211, each given twice per day and compared to placebo in participants with fibrotic NASH

Eligibility criteria: Inclusion Criteria:

1. Males or females, of any race, ≥ 18 and ≤ 75 years of age at enrolment. 2. Body mass index (BMI) of ≥ 25.0 and ≤45.0 kg/m2 3. Diagnosis of suspected NASH and liver fibrosis (Chalasani et al. 2012):

a. Evidence of hepatic steatosis within the 24 weeks prior to Screening: i. magnetic resonance imaging (MRI PDFF) suggesting liver fat ≥ 8% or ii. ultrasound (US) indicating fatty liver or iii. FibroScan Controlled Attenuation Parameter (CAP) \> 270 dB/m. iv. in participants without a documented history of fatty liver, a FibroScan CAP or US can be performed at Screening. Participants with FibroScan CAP \> 270 dB/m or US indicating fatty liver are eligible AND b. Metabolic risk factors: i. Metabolic syndrome (Adult Treatment Panel III definition) requires three or more of the following five disorders (Grundy et al. 2005):

1. elevated waist circumference (≥102 cm in men and ≥88 cm in women),
2. hypertriglyceridemia (≥1.7 mmol/l),
3. low HDL cholesterol level (\<1.03 mmol/l in men and \<1.3 mmol/l in women),
4. high blood pressure (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg and/or pharmacological treatment)
5. elevated fasting glucose (≥5.6 mmol/l and/or pharmacological treatment) ii. OR T2DM (defined as stable diabetes with glycosylated haemoglobin \[HbA1c\] ≤ 9.5%) OR A diagnosis of confirmed NASH and liver fibrosis based on a biopsy within 12-months of Screening

4. Liver stiffness as measured by transient elastography (FibroScan) ≥ 8.5 KPa 5. Women of non-childbearing potential defined as permanently sterile (see Appendix 4) or postmenopausal (see Appendix 4) or Women considered to be of childbearing potential who agree to use highly effective birth control methods until 90 days after the Follow-up visit (see Appendix 4) 6. Males will agree to use contraception throughout the study and until 90-days after the Follow-up visit 7. Male participants must agree to refrain from sperm donation and females should refrain from ova donation from the date of Randomisation (Day -1) until 90 days after the Follow up visit 8. Able to comprehend and willing to sign an ICF and to abide by the study restrictions

Exclusion Criteria:

1. Any other causes for secondary hepatic fat accumulation such as significant alcohol consumption, use of steatogenic medication or hereditary disorders
2. The following clinical laboratory results at Screening:

   1. ALT \> 200 U/L
   2. AST \> 200 U/L
3. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed)
4. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Randomisation
5. Positive hepatitis panel and/or positive HIV test
6. Evidence of acute Hepatitis A virus (HAV) and a positive serological test for anti-HAV IgM antibodies
7. Estimated glomerular filtration rate (eGFR) \< 60 mL/\[min\*1.73 m²\] at Screening
8. Use or intend to use slow release medications/products considered to still be active within 14 days prior to Randomisation, unless deemed acceptable by the Investigator (or Designee)
9. Participant taking any antidiabetic medications, with the exception of metformin and sulfonylureas within 3 months prior to Screening
10. Have previously completed or withdrawn from this study investigating GB1211 and have previously received the investigational product
11. Participant who, in the opinion of the Investigator (or Designee), should not participate in this study
12. Vulnerable/institutionalised patients
13. Patients related to PI/site staff

Primary outcomes:
measure: Safety and Tolerability of GB1211
timeFrame: 12 Weeks
measure: Safety and Tolerability of GB1211
timeFrame: 12 Weeks
measure: Safety and Tolerability of GB1211
timeFrame: 12 Weeks
Secondary outcomes:
measure: Pharmacokinetics of GB1211
timeFrame: 12 Weeks
measure: Pharmacokinetics of GB1211
timeFrame: 12 Weeks
measure: Pharmacokinetics of GB1211
timeFrame: 12 Weeks
measure: Pharmacokinetics of GB1211
timeFrame: 12 Weeks
measure: Pharmacokinetics of GB1211
timeFrame: 12 Weeks
measure: Pharmacokinetics of GB1211
timeFrame: 12 Weeks
measure: Pharmacokinetics of GB1211
timeFrame: 12 Weeks
measure: Pharmacokinetics of GB1211
timeFrame: 12 Weeks
Other outcomes:
Locations:
Study officials:
affiliation: The University of Chicago Biological Sciences
name: Michael Charlton, MD
role: PRINCIPAL_INVESTIGATOR
References: