A First in Human Study to Evaluate the Safety, Tolerability and PK of GB1211 in Healthy Subjects

NCT03809052 | Completed Phase 1 Results

• 3 other identifiers: GB1211-0012018-003914-41Covance Study Number: 8392356
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

This was a Phase 1, randomized, double-blind, placebo-controlled, first-in-human study in which the safety, tolerability, and pharmacokinetics of orally administered GB1211 will be evaluated in healthy adult subjects and adult subjects with indication of suspected Nonalcoholic steatohepatitis (NASH) and liver fibrosis.

Conditions

Safety and Tolerability

Keywords

GB1211; Phase 1; First Time in Human; Safety; Tolerability; Pharmacokinetics; Single Ascending Dose (SAD); Multiple Ascending Dose (MAD); Healthy Volunteers; Nonalcoholic Steatohepatitis (NASH); Liver Fibrosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With of Adverse Events (AEs)

  The number of participants in each arm that report Adverse Events (AEs)

  Up to 5-7 days post final dose (Part A: Single dose), Part B: 6-7 weeks

Study Arms (11)

A1 - 5 mg GB1211 single dose and Placebo

EXPERIMENTAL

6 healthy subjects are administered 5 mg of GB1211 capsules orally as a single dose in the fasted state. 2 subjects receive placebo. 2 subjects (1 active and 1 placebo) will be dosed at least 24 hours before the remaining subjects, where continuation to dose the remaining subjects will be at the Investigator's discretion.

Drug: GB1211

A2 - 20 mg GB1211 single dose and Placebo

EXPERIMENTAL

6 healthy subjects are administered 20 mg of GB1211 capsules orally as a single dose in the fasted state. 2 subjects receive placebo. 2 subjects (1 active and 1 placebo) will be dosed at least 24 hours before the remaining subjects, where continuation to dose the remaining subjects will be at the Investigator's discretion.

Drug: GB1211

A3 - 50 mg GB1211 single dose (food effect cohort) and Placebo

EXPERIMENTAL

6 healthy subjects are administered 50 mg of GB1211 capsules orally as a single dose. 2 subjects receive placebo. 2 subjects (1 active and 1 placebo) will be dosed at least 24 hours before the remaining subjects, where continuation to dose the remaining subjects will be at the Investigator's discretion. Each subject will participate in 2 treatment periods separated by a minimum of 7 days. In Treatment Period 1 doses will be administered in the fasted state, in Treatment Period 2 doses will be administered 30 minutes after the start of a high fat breakfast. Subjects will receive the same treatment in both periods.

Drug: GB1211

A4 - 100 mg GB1211 single dose and Placebo

EXPERIMENTAL

6 healthy subjects are administered 100 mg of GB1211 capsules orally as a single dose in the fasted state. 2 subjects receive placebo. 2 subjects (1 active and 1 placebo) will be dosed at least 24 hours before the remaining subjects, where continuation to dose the remaining subjects will be at the Investigator's discretion.

Drug: GB1211

A5 - 200 mg GB1211 single dose and Placebo

EXPERIMENTAL

6 healthy subjects are administered 200 mg of GB1211 capsules orally as a single dose in the fasted state. 2 subjects receive placebo. 2 subjects (1 active and 1 placebo) will be dosed at least 24 hours before the remaining subjects, where continuation to dose the remaining subjects will be at the Investigator's discretion.

Drug: GB1211

B1 - GB1211 multiple ascending doses, 50mg BID and Placebo

EXPERIMENTAL

GB1211 administered orally twice daily over 10 days. 8 healthy subjects received GB1211 and 3 subjects will receive placebo. Following review of data in Part A (Cohorts A1 to A6), subjects received twice daily (BID) doses under fasted conditions on Days 1 to 9, inclusive, and a final single dose administration on the morning of Day 10 in accordance with the randomisation schedule.

Drug: GB1211

B2 - GB1211 multiple ascending doses, 100mg BID and Placebo

EXPERIMENTAL

GB1211 administered orally twice daily over 10 days. 8 healthy subjects received GB1211 and 3 subjects will receive placebo. Following review of data in Part A (Cohorts A1 to A6), subjects received twice daily (BID) doses under fasted conditions on Days 1 to 9, inclusive, and a final single dose administration on the morning of Day 10 in accordance with the randomisation schedule..

Drug: GB1211

A6 - 50mg GB1211 single dose and Placebo

EXPERIMENTAL

8 healthy subjects are administered 50 mg (10 x 5mg capsules) or placebo without sentinel dosing. Optional cohort, as was added following dose-escalation analysis.

Drug: GB1211

A7 - 400 mg GB1211 single dose and Placebo

EXPERIMENTAL

8 healthy subjects are administered 400 mg (8 x 50mg capsules) or placebo without sentinel dosing. Optional cohort, as was added following dose-escalation analysis.

Drug: GB1211

Part A - Placebo for GB1211

EXPERIMENTAL

In Part A - 2 subjects from each arm (A1-A5) will receive placebo.

Drug: Placebo

Part B - Placebo for GB1211 (BID)

EXPERIMENTAL

Part B - 3 subjects from each arm B1 and B2 will receive placebo.

Drug: Placebo

Interventions

GB1211 DRUG

Hard capsules for oral use

A1 - 5 mg GB1211 single dose and Placebo; A2 - 20 mg GB1211 single dose and Placebo; A3 - 50 mg GB1211 single dose (food effect cohort) and Placebo; A4 - 100 mg GB1211 single dose and Placebo; A5 - 200 mg GB1211 single dose and Placebo; A6 - 50mg GB1211 single dose and Placebo; A7 - 400 mg GB1211 single dose and Placebo; B1 - GB1211 multiple ascending doses, 50mg BID and Placebo; B2 - GB1211 multiple ascending doses, 100mg BID and Placebo

Placebo DRUG

Hard capsules for oral use

Also known as: GB1211

Part A - Placebo for GB1211; Part B - Placebo for GB1211 (BID)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects for Parts A and B must satisfy all of the following criteria at the Screening visit unless otherwise stated:
• Males or females, of any race, between 18 and 55 years of age (60 years for Part B), inclusive.
• Body mass index (BMI) of 18.0 to 32.0 kg/m\^2 (inclusive) with a minimum body weight of 50 kg.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed further in the protocol.
• Male subjects must agree to refrain from sperm donation and females should refrain from ova donation from the date of Check-in (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.
• Subjects for Parts C must satisfy all of the following criteria at the Screening visit unless otherwise stated:
• Males or females, of any race, between 18 and 60 years of age, inclusive.
• Body mass index (BMI) of ≥ 25.0 and ≤ 38.0 kg/m\^2.
• Documented history of fatty liver within the last 24 weeks by one of the following: magnetic resonance imaging (MRI) suggesting liver fat ≥ 8%, ultrasound (US) indicating fatty liver, or Fibroscan Controlled Attenuation Parameter (CAP) \> 270 dB/m. In subjects without a documented history of fatty liver, a Fibroscan CAP or US can be performed at Screening. Subjects with Fibroscan CAP \> 270 dB/m or US indicating fatty liver are eligible.
• Metabolic syndrome (Adult Treatment Panel III definition) or T2DM (defined as stable diabetes with glycosylated haemoglobin \[HbA1c\] ≤ 9.5%).
• Alanine aminotransferase (ALT) ≥ 20 U/L for females and ≥ 30 U/L for males at Screening.
• Fibroscan ≥ 7 KPa and \< 13 KPa, or Fibrosis-4 (FIB-4) index ≥ 1.1 and \<3.25.
• Females of nonchildbearing potential defined as permanently sterile (ie, due to hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) or postmenopausal (defined as at least 12 months postcessation of menses without an alternative medical cause and follicle-stimulating hormone \[FSH\] level ≥ 40 mIU/mL). Males will agree to use contraception as detailed in protocol.

You may not qualify if:

• Subjects from Part A \& B will be excluded from the study if they satisfy any of the following criteria at the Screening visit unless otherwise stated:
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
• History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection.
• (Part A). Any of the following: a. QTcF \> 450 msec confirmed by repeat measurement. b. QRS duration \> 110 msec confirmed by repeat measurement. c. PR interval \> 220 msec confirmed by repeat measurement. d. findings which would make QTc measurements difficult or QTc data uninterpretable. e. history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).
• (Part B). Clinically significant ECG abnormalities or QTcF greater than 450 msec for males and 470 msec for females at either Screening or Day 1 predose, or any prior history of QT abnormality.
• \. History of alcoholism or drug/chemical abuse within 1 year prior to Check-in.
• \. Positive hepatitis panel and/or positive human immunodeficiency virus (HIV) test.
• \. Participation in a clinical study involving administration of an investigational agent or vaccine (new chemical entity) or having received a biological product in the past 90 days prior to dosing.
• \. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
• \. Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
• \. Use of tobacco- or nicotine-containing products within 3 months prior to Check-in, or positive cotinine at Screening or Check-in.
• \. Receipt of blood products within 2 months prior to Check-in and donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
• \. Subject who, in the opinion of the Investigator (or designee), should not participate in this study.
• Subjects from Part C will be excluded from the study if they satisfy any of the following criteria at the Screening visit unless otherwise stated:
• If diabetic and diabetes is other than T2DM.

Sponsors & Collaborators

• Galecto Biotech AB: lead

Study Sites (1)

(For Parts A and B) Covance Clinical Research Unit Ltd

Leeds, LS2 9LH, United Kingdom

Location

Related Publications (1)

• Aslanis V, Slack RJ, MacKinnon AC, McClinton C, Tantawi S, Gravelle L, Nilsson UJ, Leffler H, Brooks A, Khindri SK, Marshall RP, Pedersen A, Schambye H, Zetterberg F. Safety and pharmacokinetics of GB1211, an oral galectin-3 inhibitor: a single- and multiple-dose first-in-human study in healthy participants. Cancer Chemother Pharmacol. 2023 Mar;91(3):267-280. doi: 10.1007/s00280-023-04513-y. Epub 2023 Mar 13.

  PMID: 36914828 DERIVED

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

Results Point of Contact

• Title: Dr Bertil Lindmark, Chief Medical Officer
• Organization: Galecto BIotech

info@galecto.com

+45 70 70 52 10

Study Officials

• Dr Ashley Brooks, MBChB

  Covance

  PRINCIPAL INVESTIGATOR

• Dr Bertil Lindmark MD PHD, Chief Medical Officer

  Galecto Biotech AB

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: 56 subjects will be studied in 7 cohorts (Cohorts A1 to A7) Part B: 22 subjects will be studied in 2 cohorts (Cohorts B1 to B2)

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: January 18, 2019
• Study Start: January 14, 2019
• Primary Completion: June 25, 2019
• Study Completion: June 25, 2019
• Last Updated: March 17, 2021
• Results First Posted: February 23, 2021

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)