A Single and Repeat Dose Trial in Participants With Hepatic Impairment

NCT05009680 | Unknown Phase 1 DMC

• 1 other identifier: GULLIVER-2
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 4

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)

Conditions

Hepatic Impairment

Keywords

Child Pugh B; Child Pugh C; Liver Cirrhosis; Galectin 3 Inhibitor

Outcome Measures

Primary Outcomes (3)

• Parts 1 Safety and Tolerability of GB1211

  Incidence and severity of adverse events as reported by investigators

  11 Days

• Parts 2 Safety and Tolerability of GB1211

  Incidence and severity of adverse events as reported by investigators

  12 Weeks

• Parts 3 Safety and Tolerability of GB1211

  Incidence and severity of adverse events as reported by investigators

  11 Days

Secondary Outcomes (3)

• Part 2 Collagen Production and Breakdown Biomarkers

  12 Weeks

• Part 2 Changes on liver and spleen stiffness

  12 Weeks

• Part 2 Changes in Liver Functional Capacity

  12 Weeks

Study Arms (6)

Part 1 GB1211, Single Dose (Child Pugh B)

EXPERIMENTAL

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

Drug: GB1211

Part 1 GB1211 Healthy Matched Participants, Single Dose

EXPERIMENTAL

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

Drug: GB1211

Part 2 GB1211 Multiple Dose, Twice a day (Child Pugh B)

EXPERIMENTAL

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

Drug: GB1211

Part 2 Placebo, Twice a day (Child Pugh B)

PLACEBO COMPARATOR

Placebo is administered twice daily

Drug: Placebo

Part 1 GB1211, Single Dose (Child Pugh C)

EXPERIMENTAL

Part 1 GB1211 Healthy Matched Participants, Single Dose

Drug: GB1211

Part 3 GB1211 Healthy Matched Participants, Single Dose

EXPERIMENTAL

Part 1 GB1211 Healthy Matched Participants, Single Dose

Drug: GB1211

Interventions

GB1211 DRUG

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

Part 1 GB1211 Healthy Matched Participants, Single Dose; Part 1 GB1211, Single Dose (Child Pugh B); Part 1 GB1211, Single Dose (Child Pugh C); Part 2 GB1211 Multiple Dose, Twice a day (Child Pugh B); Part 3 GB1211 Healthy Matched Participants, Single Dose

Placebo DRUG

Placebo is administered orally twice a day

Part 2 Placebo, Twice a day (Child Pugh B)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• 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
• Body mass index (BMI) of ≥ 18-40 kg/m2
• Participants with hepatic impairment:
• 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
• 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
• Healthy participants (controls) in PART 1 and PART 3:
• Healthy as determined by the investigator, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac assessment
• 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)
• Women of non-childbearing potential defined as permanently sterile or postmenopausal
• Males will agree to use contraception throughout the study and until 90-days after the Follow-up visit
• Male participants must agree to refrain from sperm donation from the date of Randomisation (Day 1) until 90 days after the Follow up visit
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions

You may not qualify if:

• All parts and all groups (control healthy volunteers and hepatic impairment)
• History of an organ transplant, including a remote history of bone marrow transplant
• History of febrile illness within 7 days prior to the first dose of study drug or participants with evidence of active infection
• Use of any oral glucocorticoids at any dose within 30 days prior to Screening and until study completion
• Have previously completed or withdrawn from a 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 Principal Investigator (PI)/site staff
• If female, the participant is of child-bearing potential
• 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.
• 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
• Donation or loss of ≥ 400 mL blood or plasma less than 4 weeks prior to screening, or longer if required by local regulations
• Positive HIV test
• Have received live vaccine(s) within 30 days prior to Screening or who will require a vaccine(s) and until study completion
• 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

Sponsors & Collaborators

• Galecto Biotech AB: lead
• Comac Medical: collaborator

Study Sites (4)

COAMC Medical

Sofia, 1000, Bulgaria

Location

Gastroenterology Clinic, Lozenets district

Sofia, 1407, Bulgaria

Location

Diagnostic-Advisory center 'ALEKSANDROVSKA" Ltd

Sofia, 1431, Bulgaria

Location

University Multiprofile Hospital, Clinic of gastroenterology

Sofia, Оborishte District, 1527, Bulgaria

Location

Related Publications (1)

• Aslanis V, Gray M, Slack RJ, Zetterberg FR, Tonev D, Phung D, Smith B, Jacoby B, Schambye H, Krastev Z, Ungell AL, Lindmark B. Single-Dose Pharmacokinetics and Safety of the Oral Galectin-3 Inhibitor, Selvigaltin (GB1211), in Participants with Hepatic Impairment. Clin Drug Investig. 2024 Oct;44(10):773-787. doi: 10.1007/s40261-024-01395-7. Epub 2024 Oct 2.

  PMID: 39358661 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Zahariy Krastev, MD

  Comac Medical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Parts 1 \& 3 - Open Label, Single Dose Part 2 - Double-blind. The blinding will be maintained throughout the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parts 1 \& 3 Open Label, Single Dose Part 2 Randomised to either GB1211 or Placebo

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: August 17, 2021
• Study Start: September 9, 2021
• Primary Completion: July 18, 2022
• Study Completion: July 4, 2023
• Last Updated: May 11, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

BU (4)