Clinical trial NCT05009680: A Single and Repeat Dose Trial in Participants With Hepatic Impairment
Official title: GULLIVER-2 - A Single (Open-label) and Repeat Dose (Randomised, Placebo-controlled) Trial to Assess the Safety, Tolerability and Pharmacokinetics of GB1211 in Participants With Hepatic Impairment (Child Pugh B & C)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hepatic Impairment
Keywords: Child Pugh B
Child Pugh C
Liver Cirrhosis
Galectin 3 Inhibitor
Lead sponsor: Galecto Biotech AB
Sponsor class: INDUSTRY
Collaborators: name: Comac Medical
First posted: 2021-08-17
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parts 1 \& 3 Open Label, Single Dose Part 2 Randomised to either GB1211 or Placebo
Primary purpose: TREATMENT

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).

Eligibility criteria: 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 exclusion criteria for matched healthy control subjects:
17. Use of any prescription or non-prescription medication (OTC), herbal medication, dietary supplements or vitamins during 30 days prior to dosing. Acetaminophen is acceptable
18. History or presence of liver disease or liver injury as indicated by an abnormal liver function profile such as AST, ALT, alkaline phosphatase, or serum bilirubin
19. A positive Hepatitis C test or a positive Hepatitis B surface antigen (HBsAg)
20. Estimated glomerular filtration rate (eGFR) \< 80 mL/\[min\*1.73 m²\] (estimated using the Modification of Diet in Renal Disease \[MDRD\] equation) at Screening

    Additional exclusion criteria for hepatic impaired subjects:

    Participants meeting any of the following exclusion criteria are not to be enrolled in the study/randomised to treatment:
21. History of any known serious disease (such as cancer, except skin basal cell carcinomas, major infection, clinically significant gastrointestinal disorder, major autoimmune disease) or other disease which in the Investigator's opinion would exclude the patient from the study
22. Estimated glomerular filtration rate (eGFR) \< 40 mL/\[min\*1.73 m²\] (estimated using the \[MDRD\] equation) at Screening
23. Use of any hepatotoxic drug (e.g. methotrexate, isoniazid, amiodarone) within 30 days of Screening and until study completion
24. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, or other putatively hepatoprotective herbal remedies such as milk thistle derivatives, within 30 days prior to dosing, unless deemed acceptable by the Investigator (or Designee). Milk thistle derivates or other hepatoprotective herbal remedies are allowed if stable dose is administered 30 days before dosing
25. 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)

Primary outcomes:
measure: Parts 1 Safety and Tolerability of GB1211
timeFrame: 11 Days
measure: Parts 2 Safety and Tolerability of GB1211
timeFrame: 12 Weeks
measure: Parts 3 Safety and Tolerability of GB1211
timeFrame: 11 Days
Secondary outcomes:
measure: Part 2 Collagen Production and Breakdown Biomarkers
timeFrame: 12 Weeks
measure: Part 2 Changes on liver and spleen stiffness
timeFrame: 12 Weeks
measure: Part 2 Changes in Liver Functional Capacity
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: COAMC Medical
city: Sofia
country: Bulgaria
facility: Gastroenterology Clinic, Lozenets district
city: Sofia
country: Bulgaria
facility: Diagnostic-Advisory center 'ALEKSANDROVSKA" Ltd
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital, Clinic of gastroenterology
state: Оborishte District
Study officials:
affiliation: Comac Medical
name: Zahariy Krastev, MD
role: PRINCIPAL_INVESTIGATOR
References: