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

Non-alcoholic Steatohepatitis (NASH) Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04607655
• Other study ID #: GULLIVER-1
• Secondary ID: 2020-000687-34
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: March 2021
• Est. completion date: July 2022

Study information

• Verified date: October 2020
• Source: Galecto Biotech AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• Liver Cirrhosis
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis (NASH)

Intervention

Drug:
• GB1211
GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.
• Placebo
Placebo is administered as inhalation once a day

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Galecto Biotech AB	Covance

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of GB1211	Incidence and severity of adverse events as reported by investigators	12 Weeks
Primary	Safety and Tolerability of GB1211	Incidence of laboratory abnormalities as measured by haematology, clinical chemistry and urinalysis	12 Weeks
Primary	Safety and Tolerability of GB1211	Physical examination abnormalities measured by vital signs and 12 lead ECG	12 Weeks
Secondary	Pharmacokinetics of GB1211	AUC over a dosing interval (AUC0-t)	12 Weeks
Secondary	Pharmacokinetics of GB1211	Cmax	12 Weeks
Secondary	Pharmacokinetics of GB1211	Tmax	12 Weeks
Secondary	Pharmacokinetics of GB1211	t1/2	12 Weeks
Secondary	Pharmacokinetics of GB1211	Minimum observed plasma concentration (Cmin)	12 Weeks
Secondary	Pharmacokinetics of GB1211	Observed accumulation ratio based on AUC0-t (RAAUC0-t)	12 Weeks
Secondary	Pharmacokinetics of GB1211	Observed accumulation ratio based on Cmax (RACmax)	12 Weeks
Secondary	Pharmacokinetics of GB1211	Volume of distribution and rate of elimination	12 Weeks