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

NCT04607655 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: GULLIVER-12020-000687-34
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Conditions

Non-alcoholic Steatohepatitis (NASH)

Keywords

GB1211; Non-alcoholic Steatohepatitis; NASH; Liver Fibrosis; Galectin-3 Inhibitor

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Pharmacokinetics of GB1211

  12 Weeks

• Pharmacokinetics of GB1211

  12 Weeks

• Pharmacokinetics of GB1211

  12 Weeks

• Pharmacokinetics of GB1211

  12 Weeks

• Pharmacokinetics of GB1211

  12 Weeks

Study Arms (3)

Oral GB1211, 100 mg, twice a day

EXPERIMENTAL

GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.

Drug: GB1211

Oral GB1211, 10 mg, twice a day

EXPERIMENTAL

GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.

Drug: GB1211

Oral GB1211, Placebo, twice a day

PLACEBO COMPARATOR

Placebo is administered as inhalation once a day

Drug: Placebo

Interventions

GB1211 DRUG

GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day.

Oral GB1211, 10 mg, twice a day; Oral GB1211, 100 mg, twice a day

Placebo DRUG

Placebo is administered as inhalation once a day

Oral GB1211, Placebo, twice a day

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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):
• elevated waist circumference (≥102 cm in men and ≥88 cm in women),
• hypertriglyceridemia (≥1.7 mmol/l),
• low HDL cholesterol level (\<1.03 mmol/l in men and \<1.3 mmol/l in women),
• high blood pressure (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg and/or pharmacological treatment)
• 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
• \. 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

You may not qualify if:

• Any other causes for secondary hepatic fat accumulation such as significant alcohol consumption, use of steatogenic medication or hereditary disorders
• The following clinical laboratory results at Screening:
• ALT \> 200 U/L
• AST \> 200 U/L
• 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)
• Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Randomisation
• Positive hepatitis panel and/or positive HIV test
• Evidence of acute Hepatitis A virus (HAV) and a positive serological test for anti-HAV IgM antibodies
• Estimated glomerular filtration rate (eGFR) \< 60 mL/\[min\*1.73 m²\] at Screening
• 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)
• Participant taking any antidiabetic medications, with the exception of metformin and sulfonylureas within 3 months prior to Screening
• Have previously completed or withdrawn from this study investigating GB1211 and have previously received the investigational product
• Participant who, in the opinion of the Investigator (or Designee), should not participate in this study
• Vulnerable/institutionalised patients
• Patients related to PI/site staff

Sponsors & Collaborators

• Galecto Biotech AB: lead
• Covance: collaborator

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Charlton, MD

  The University of Chicago Biological Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is a double-blind study. The blinding will be maintained throughout the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: October 29, 2020
• Study Start: March 1, 2021
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: February 4, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share