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

Sponsor
Galecto Biotech AB (Industry)
Overall Status
Withdrawn
CT.gov ID
NCT04607655
Collaborator
Covance (Industry)
0
3
16

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
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 dayAll subjects eligible for the study will be randomised into one of the three treatment arms:GB1211 100 mg twice a day B. GB1211 10 mg twice a day C. Placebo twice a day
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
This study is a double-blind study. The blinding will be maintained throughout the study.
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Mar 1, 2021
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Safety and Tolerability of GB1211 [12 Weeks]

    Incidence and severity of adverse events as reported by investigators

  2. Safety and Tolerability of GB1211 [12 Weeks]

    Incidence of laboratory abnormalities as measured by haematology, clinical chemistry and urinalysis

  3. Safety and Tolerability of GB1211 [12 Weeks]

    Physical examination abnormalities measured by vital signs and 12 lead ECG

Secondary Outcome Measures

  1. Pharmacokinetics of GB1211 [12 Weeks]

    AUC over a dosing interval (AUC0-τ)

  2. Pharmacokinetics of GB1211 [12 Weeks]

    Cmax

  3. Pharmacokinetics of GB1211 [12 Weeks]

    Tmax

  4. Pharmacokinetics of GB1211 [12 Weeks]

    t1/2

  5. Pharmacokinetics of GB1211 [12 Weeks]

    Minimum observed plasma concentration (Cmin)

  6. Pharmacokinetics of GB1211 [12 Weeks]

    Observed accumulation ratio based on AUC0-τ (RAAUC0-τ)

  7. Pharmacokinetics of GB1211 [12 Weeks]

    Observed accumulation ratio based on Cmax (RACmax)

  8. Pharmacokinetics of GB1211 [12 Weeks]

    Volume of distribution and rate of elimination

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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):
  1. 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

  6. 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:

  3. ALT > 200 U/L

  4. AST > 200 U/L

  5. 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)

  6. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Randomisation

  7. Positive hepatitis panel and/or positive HIV test

  8. Evidence of acute Hepatitis A virus (HAV) and a positive serological test for anti-HAV IgM antibodies

  9. Estimated glomerular filtration rate (eGFR) < 60 mL/[min*1.73 m²] at Screening

  10. 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)

  11. Participant taking any antidiabetic medications, with the exception of metformin and sulfonylureas within 3 months prior to Screening

  12. Have previously completed or withdrawn from this study investigating GB1211 and have previously received the investigational product

  13. Participant who, in the opinion of the Investigator (or Designee), should not participate in this study

  14. Vulnerable/institutionalised patients

  15. Patients related to PI/site staff

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Galecto Biotech AB
  • Covance

Investigators

  • Principal Investigator: Michael Charlton, MD, The University of Chicago Biological Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Galecto Biotech AB
ClinicalTrials.gov Identifier:
NCT04607655
Other Study ID Numbers:
  • GULLIVER-1
  • 2020-000687-34
First Posted:
Oct 29, 2020
Last Update Posted:
Feb 4, 2021
Last Verified:
Oct 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Galecto Biotech AB
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 4, 2021