Hepatic Impairment
Conditions
Keywords
Child Pugh B, Child Pugh C, Liver Cirrhosis, Galectin 3 Inhibitor
Brief summary
This study is a a single (open-label) and repeat dose (randomised, placebo controlled) trial to assess the safety, tolerability and pharmacokinetics of GB1211 (Gal-3 inhibitor) in participants with hepatic impairment (Child Pugh B and Child Pugh C)
Detailed description
PART 1 A single dose, open-label safety and PK study of GB1211 administered to participants with moderate hepatic impairment (Child Pugh B) and to matched healthy participants (controls). PART 2 A randomised, double-blind, placebo-controlled study in participants with moderate hepatic impairment (Child Pugh B). GB1211 or placebo will be administered daily for 12 weeks. PART 3 A single dose, open-label safety and PK study of GB1211 administered to participants with severe hepatic impairment (Child Pugh C) and to healthy participants (controls).
Interventions
DRUGGB1211
GB1211 is a galectin-3 inhibitor an orally available small molecule anti-fibrotic. It is administered orally twice a day
DRUGPlacebo
Placebo is administered orally twice a day
Sponsors
Comac Medical
Galecto Biotech AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Parts 1 & 3 - Open Label, Single Dose Part 2 - Double-blind. The blinding will be maintained throughout the study.
Intervention model description
Parts 1 & 3 Open Label, Single Dose Part 2 Randomised to either GB1211 or Placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: 1. Males or females, of any race, ≥ 18 and ≤ 75 years of age at enrolment 2. Body mass index (BMI) of ≥ 18-40 kg/m2 3. Participants with hepatic impairment: 1. PART 1 and PART 2: Moderate hepatic impairment, as defined by the Child-Pugh score (Child-Pugh B) \[1\] who exhibit physical signs consistent with stable hepatic impairment and free of significant medical disorders unrelated to their hepatic disorder and are on stable concomitant medication for 2 weeks prior to and for the duration of this study 2. PART 3: Severe hepatic impairment as defined by the Child-Pugh score (Child Pugh C) who exhibit physical signs consistent with stable hepatic impairment and free of significant medical disorders unrelated to their hepatic disorder and are on stable concomitant medication for 2 weeks prior to and for the duration of this study 4. Healthy participants (controls) in PART 1 and PART 3: 1. Healthy as determined by the investigator, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac assessment 2. Match at least one of the participants with moderate or severe hepatic impairment with respect to gender, age (±10 years), and body mass index (BMI) ± 15% (ensure every participant with hepatic impairment has at least 1 matched control) 5. Women of non-childbearing potential defined as permanently sterile or postmenopausal 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 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
All parts and all groups (control healthy volunteers and hepatic impairment) 1. History of an organ transplant, including a remote history of bone marrow transplant 2. History of febrile illness within 7 days prior to the first dose of study drug or participants with evidence of active infection 3. Use of any oral glucocorticoids at any dose within 30 days prior to Screening and until study completion 4. Have previously completed or withdrawn from a study investigating GB1211 and have previously received the investigational product 5. Participant who, in the opinion of the Investigator (or Designee), should not participate in this study 6. Vulnerable/institutionalised patients 7. Patients related to Principal Investigator (PI)/site staff 8. If female, the participant is of child-bearing potential 9. Participation in a clinical study involving administration of an investigational agent e.g. new chemical entity or a biological product in the past 90 days (or 5 multiples of half-life, whichever is longer) prior to dosing. 10. Medical history of cardiac disease and/or clinically significant ECG abnormalities. An abnormal ECG is defined as PR \> 220 msec, QRS complex \>120 msec, QTcF \> 450 msec (males) and \> 470msec (females), or any other morphological changes, other than nonspecific T-wave changes 11. Donation or loss of ≥ 400 mL blood or plasma less than 4 weeks prior to screening, or longer if required by local regulations 12. Positive HIV test 13. Have received live vaccine(s) within 30 days prior to Screening or who will require a vaccine(s) and until study completion 14. Use of any medications/products that may inhibit biliary excretion, e.g. bile salt chelators, mycophenolic acid, warfarin, and digoxin, within 30 days prior to Screening and until study completion 15. Use of any medications/products that may inhibit renal excretion; e.g. cimetidine, pyrimethamine, dolutegravir, probenecid, within 30 days prior to Screening and until study completion 16. Use of any medications/products that are known inhibitors of P-gp (e.g. clarithromycin, fostamatinib, quinidine, quinine) and inducers of P-gp (e.g. carbmazepine, rifampin, St. John's wort) within 30 days prior to Screening and until study completion Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 Safety and Tolerability of GB1211 | 11 Days | Incidence and severity of adverse events as reported by investigators |
| Parts 2 Safety and Tolerability of GB1211 | 12 Weeks | Incidence and severity of adverse events as reported by investigators |
| Parts 3 Safety and Tolerability of GB1211 | 11 Days | Incidence and severity of adverse events as reported by investigators |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2 Collagen Production and Breakdown Biomarkers | 12 Weeks | Assessment of liver fibrosis using pro-C3, CK18 and PAI-1 Biomarkers |
| Part 2 Changes on liver and spleen stiffness | 12 Weeks | Assessment of liver and spleen stiffness measured by vibration control transient elastography |
| Part 2 Changes in Liver Functional Capacity | 12 Weeks | Assessment of Liver functional Capacity measured by 13C methacetin breath test |
Countries
Bulgaria
Outcome results
None listed