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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Non-alcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: Placebo; Drug: GB1211

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

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Oral GB1211, 100 mg, twice a day; GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.	Drug: GB1211; GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.
EXPERIMENTAL: Oral GB1211, 10 mg, twice a day; GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.	Drug: GB1211; GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.
PLACEBO_COMPARATOR: Oral GB1211, Placebo, twice a day; Placebo is administered as inhalation once a day	Drug: Placebo; Placebo is administered as inhalation once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of GB1211	Incidence and severity of adverse events as reported by investigators	12 Weeks
Safety and Tolerability of GB1211	Incidence of laboratory abnormalities as measured by haematology, clinical chemistry and urinalysis	12 Weeks
Safety and Tolerability of GB1211	Physical examination abnormalities measured by vital signs and 12 lead ECG	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of GB1211	AUC over a dosing interval (AUC0-τ)	12 Weeks
Pharmacokinetics of GB1211	Cmax	12 Weeks
Pharmacokinetics of GB1211	Tmax	12 Weeks
Pharmacokinetics of GB1211	t1/2	12 Weeks
Pharmacokinetics of GB1211	Minimum observed plasma concentration (Cmin)	12 Weeks
Pharmacokinetics of GB1211	Observed accumulation ratio based on AUC0-τ (RAAUC0-τ)	12 Weeks
Pharmacokinetics of GB1211	Observed accumulation ratio based on Cmax (RACmax)	12 Weeks
Pharmacokinetics of GB1211	Volume of distribution and rate of elimination	12 Weeks

Collaborators and Investigators

• Sponsor: Galecto Biotech AB
• Collaborators: Covance
• Investigators: Principal Investigator: Michael Charlton, MD, The University of Chicago Biological Sciences

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2021
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): July 1, 2022

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (ACTUAL): October 29, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: NASH; Liver Fibrosis; Non-alcoholic Steatohepatitis; GB1211; Galectin-3 Inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: GULLIVER-1; 2020-000687-34 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No