Study Evaluating the Efficacy and Safety of Belapectin (GR-MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Galectin Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

8 Mar 2021 → 11 Mar 2025

Decision date (initial)

2024-05-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Galectin Therapeutics Inc.

External identifiers

EU CT number

2024-512619-28-00

EudraCT number

2019-001983-31

ClinicalTrials.gov

NCT04365868

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety, Pharmacodynamic, Pharmacokinetic

To evaluate the efficacy of 2 mg/kg and 4 mg/kg lean body mass (LBM) of belapectin (GR MD 02) compared to placebo in preventing the development of esophageal varices.

Secondary objectives 1

1. To evaluate the effect of belapectin on composite clinical outcomes.

Conditions and MedDRA coding

Esophageal Varices in NASH Cirrhosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male or female, ≥ 18 and ≤ 75 years old.
2. Willing and able to provide written informed consent.
3. Has evidence of portal hypertension, with either one: a.platelet count <150K/mm3 (from central laboratory or historical record, e.g. detailed chart notes providing platelet numbers or copies of laboratory reports showing platelet count[s] below 150K/mm3) OR b.documented HVPG measurement >6 mmHg OR c.at least two of the following: -spleen size ≥ 14 cm -abdominal collateral circulation -documented liver transient elastography ≥20 kPa -AST/ALT >1.
4. History confirming NASH cirrhosis, with at least one: •Historical liver biopsy showing cirrhosis with steatohepatitis (if slides or blocks are not available, the biopsy report must clearly indicate cirrhosis with steatohepatitis). •Historical liver biopsy showing steatohepatitis (if slides or blocks are not available, the biopsy report must clearly indicate steatohepatitis), and there is evidence of cirrhosis from clinical or imaging data or a second liver biopsy showing cirrhosis without all features of NASH. There is no evidence for a competing etiology. There is at least 1 coexisting or history of metabolic comorbidity at Screening: obesity (with either body mass index [BMI] ≥30 kg/m2 or waist circumference ≥102 cm [40 in, men] or ≥88 cm [35 in, women], or by ethnically appropriate cutpoints); hypertension (either on anti hypertensive drug therapy for at least 1 year or systolic/diastolic BP >140/80 mm Hg); Type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.5%, or on anti-diabetic medication for at least 1 year); or dyslipidemia (triglycerides ≥150 mg/dL or on drug therapy for hypertriglyceridemia for at least 6 months; high-density lipoprotein cholesterol ≤40 mg/dL [men] or ≤50 mg/dL [women]) to corroborate a diagnosis of NAFLD. •Historical liver biopsy showing cirrhosis with steatosis but not steatohepatitis (if slides or blocks are not available, the biopsy report must clearly indicate cirrhosis with steatosis). •Historical liver biopsy showing steatosis (if slides or blocks are not available, the biopsy report must clearly indicate steatosis) but now with cirrhosis either by physical examination, imaging, or biopsy. There is no evidence for a competing etiology. There are at least 2 co existing (or history of) metabolic comorbidities (with obesity or diabetes being one of them) to corroborate a diagnosis of NAFLD. •Patient with cirrhosis with current or previous imaging showing steatosis. There is no liver histology available. There is no evidence for a competing etiology. There are at least two co-existing or history of metabolic comorbidities with obesity or diabetes being one of them to corroborate a diagnosis of NAFLD. •For patients not meeting the above mentioned criteria, a screening liver biopsy is necessary.
5. Absence of HCC by valid imaging within 6 months prior to randomization.
6. Patients with type 2 diabetes mellitus can be enrolled, if they are adequately controlled on a stable of antidiabetic medication(s) for at least 3 months before Screening, with screening HbA1c ≤9.5%.
7. Patients on therapeutic doses of vitamin E or pioglitazone can be enrolled if were on a stable regimen for at least 3 months before screening, and regimen is expected to be held constant during the trial.
8. Patients on a statin can be enrolled if they are on a stable dose and regimen for at least 3 months before Screening, and the dose is expected to be held constant during the trial.
9. Is not pregnant and has a negative serum pregnancy test result prior to randomization.
10. Is of non-childbearing potential or if a fertile man or woman participating in heterosexual relations, agrees to use effective means of contraception (ie, 2 effective methods of contraception, one of which must be a physical barrier method).
11. Lactating woman: agrees to discontinue nursing before the start of study treatment and refrain from nursing 90 days after the last dose of study treatment.
12. Man: agrees to refrain from sperm donation throughout the study period and 90 days after the last dose of investigational medicinal product (IMP). Female: may not begin a cycle of ova donation or harvest throughout the study period and 90 days following the last dose of IMP.

Exclusion criteria 21

1. Presence of esophageal, gastroesophageal, or isolated gastric varices, based on an upper GI EGD exam conducted during Screening. Patients with portal hypertensive gastropathy could be enrolled.
2. History of hepatic cirrhosis decompensation including any episode of variceal bleeding, ascites not controlled by medication, spontaneous bacterial peritonitis or overt hepatic encephalopathy (West Haven grade ≥2 as assessed by the principal investigator), OR develops signs of hepatic cirrhosis decompensation during Screening.
3. Known or suspected abuse of alcohol, as per medical history.
4. Alcohol dependence.
5. Narcotics or any other drug abuse or dependence in the last 5 years
6. Prior trans-jugular intrahepatic portal-systemic (TIPS) shunt procedure.
7. Documented causes of chronic liver disease other than NASH, including but not restricted to: •Viral hepatitis, unless eradicated at least 3 years prior to Screening •acute hepatitis A infection (presence of hepatitis A immunoglobulin M [IgM] at Screening) •positive hepatitis B surface antigen •positive hepatitis C virus (HCV) ribonucleic acid (to be performed prior to randomization in case of positive HCV antibody) •Documented of drug-induced liver disease •Alcoholic liver disease •Autoimmune hepatitis •Wilson's disease •Hemochromatosis •Primary biliary cholangitis (also termed primary biliary cirrhosis) •Primary sclerosing cholangitis •Genetic hemochromatosis •Known or suspected HCC •History or planned liver transplantation, or current MELD score ≥12 •Alpha-1 antitrypsin deficiency
8. History of human immunodeficiency virus (HIV), or positive HIV test at Screening.
9. Any of the following test or score values during Screening Visit (SV) 1, SV2, and SV3 (if required/available): •serum ALT > 5 × upper limit of normal (ULN) •serum AST > 5 × ULN •serum ALP > 2 × ULN •mean platelet count < 150,000/mm3 •albumin ≤ 3.5 g/dL •INR ≥1.5 (without anticoagulant therapy) •total bilirubin ≥ 2.0 mg/dL (subjects with a documented history of Gilbert's syndrome can be enrolled if the direct bilirubin is within normal reference range) •MELD score >12 (patients on warfarin will be exempt from this criterion) •CTP Score ≥7 •estimated creatinine clearance < 45 mL/min
10. Taking an angiotensin converting enzyme inhibitor, angiotensin II receptor blocker, or β-1 selective adrenergic receptor inhibitor, unless on a stable dose and dosing regimen for at least 3 months prior to Screening, and no changes in the dose or dosing regimen are anticipated during the entire study. Subjects taking a non-selective beta blocker are not eligible to be enrolled (Investigators are encouraged to substitute another medication, if clinically warranted).
11. History of major surgery during the Screening.
12. History of a solid organ transplant requiring continuing immunosuppressive therapy.
13. History of bariatric surgery within 1 year of randomization, or plan to undergo bariatric surgery during the study.
14. Has positive screening test for illicit drugs of abuse at Screening. Positive marijuana/cannabinoids (THC) usage is not an automatic exclusion, but rather should be based upon local requirements where applicable.
15. Has participated in an investigational new drug study within 30 days or 5 half-lives whichever is longer, prior to randomization (including follow-up visits) or at any time during the current study.
16. Has a history of malignancy within 5 years of randomization, except for basal cell carcinoma, squamous cell carcinoma and adequately treated in situ uterine cervical cancer.
17. Has clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction within 6 months prior to randomization, unstable angina), New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring intervention (eg, pacemaker/ablation) or Grade II or greater peripheral vascular disease within 12 months prior to randomization.
18. Has a history of clinically significant hematologic, renal, hepatic, pulmonary, neurological, psychiatric, gastrointestinal, systemic inflammatory, metabolic or endocrine disorder or any other condition that, in the opinion of the Investigator, renders the subject a poor candidate for inclusion into the study.
19. Has known allergies to the IMP or any of its excipients.
20. Has previously received belapectin within 6 months of randomization.
21. Is an employee or family member of the Investigator or study center personnel.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients in the belapectin treatment groups who develop esophageal varices at 78 weeks (18 months) of treatment compared to placebo.

Secondary endpoints 1

1. Incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop any of:1)varices (esophageal or gastric) requiring treatment,2)variceal bleed requiring hospitalization,3)clinically significant ascites requiring hospitalization,4)spontaneous bacterial peritonitis,5)overt hepatic encephalopathy (West Haven score ≥2 and requiring hospitalization),6)mortality(all-cause),7)liver transplant,8)model for end-stage liver disease(MELD)score ≥15 on 2 consecutive occasions.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Galectin Therapeutics Inc.

Sponsor organisation

Galectin Therapeutics Inc.

Address

4960 Peachtree Industrial Boulevard Suite 240

City

Berkeley Lake

Postcode

30071-1580

Country

United States

Scientific contact point

Organisation

Galectin Therapeutics Inc.

Contact name

Susan Thornton

Public contact point

Organisation

Galectin Therapeutics Inc.

Contact name

Susan Thornton

Third parties 11

Locations

5 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications