Clinical Trials Register

Summary
EudraCT Number:	2019-001983-31
Sponsor's Protocol Code Number:	GT-031
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-12-29
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2019-001983-31

A.3

Full title of the trial

A Seamless, Adaptive, Phase 2b/3, Double-Blind, Randomized, Placebo-controlled, Multicenter, International Study Evaluating the Efficacy and Safety of Belapectin (GR MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis.

Elastyczne, adaptacyjne, prowadzone metodą podwójnie ślepej próby, randomizowane, wieloośrodkowe, międzynarodowe badanie fazy IIb/III z grupą kontrolną otrzymującą placebo, oceniające skuteczność i bezpieczeństwo stosowania leku badanego Belapectin (GR-MD-02) w zapobieganiu żylakom przełyku w marskości wątroby spowodowanej przez niealkoholowe stłuszczeniowe zapalenie wątroby (NASH)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Badanie oceniające skuteczność i bezpieczeństwo stosowania leku badanego Belapectin (GR-MD-02) w zapobieganiu żylakom przełyku w marskości wątroby spowodowanej przez niealkoholowe stłuszczeniowe zapalenie wątroby (NASH).

A.3.2

Name or abbreviated title of the trial where available

NASH-RX

A.4.1

Sponsor's protocol code number

GT-031

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Galectin Therapeutics Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Galectin Therapeutics Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Galectin Therapeutics Inc.
B.5.2	Functional name of contact point	Steve Schoenfeld
B.5.3	Address:
B.5.3.1	Street Address	4960 Peachtree Industrial Boulevard; Suite 240
B.5.3.2	Town/ city	Norcross, Georgia
B.5.3.3	Post code	30071
B.5.3.4	Country	United States
B.5.6	E-mail	schoenfeld@galectintherapeutics.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Belapectin
D.3.2	Product code	GR-MD-02
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N.A.
D.3.9.1	CAS number	1980787-47-0
D.3.9.2	Current sponsor code	GR-MD-02
D.3.9.3	Other descriptive name	Galactoarabino-rhamnogalacturonate
D.3.9.4	EV Substance Code	SUB204211
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	27
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Esophageal Varices in NASH Cirrhosis

E.1.1.1

Medical condition in easily understood language

Varices (enlarged veins) in oesophagus (muscular tube connecting the throat with the stomach) in patients with liver cirrhosis (scarring) due to non-alcoholic fatty liver disease with inflammation.

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10009214
E.1.2	Term	Cirrhosis of liver without mention of alcohol
E.1.2	System Organ Class	100000004871

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10055489
E.1.2	Term	Esophageal varices in cirrhosis of liver
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

To evaluate the effect of belapectin on composite clinical outcomes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Is male or female, ≥ 18 and ≤ 75 years of age at the time of Screening.
2. Is willing and able to provide written informed consent prior to the
initiation of any study-specific procedures.
Has evidence of portal hypertension, with
3. either one of the following:
a. platelet count <150,000/mm3
OR
b. documented HVPG measurement >6 mmHg
OR
c. at least two of the following:
- spleen size ≥ 14 cm (documented by ultrasound, MRI, or CT scan)
- abdominal collateral circulation (documented by ultrasound, MRI, or CT
scan, or physical examination, ie, caput medusae)
- documented liver transient elastography (eg, FibroScan) ≥20 kPa
- AST/ALT >1.
4. Has a history confirming NASH cirrhosis, with at least one of the following:
• There is a historical liver biopsy showing cirrhosis with steatohepatitis. There is no evidence for a competing etiology for the cirrhosis.
• There is a historical liver biopsy showing steatohepatitis, and there is evidence of cirrhosis from clinical or imaging data or a second liver biopsy showing cirrhosis without all features of NASH (as the histological NASH lesions may have burnt out). There is no evidence for a competing etiology. There is at least 1 co-existing 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.
• There is a historical liver biopsy showing cirrhosis with steatosis but not steatohepatitis. 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.
• There is a historical liver biopsy showing steatosis but now with cirrhosis either by physical examination, imaging, or biopsy. If there is a current biopsy, it does not show evidence of steatosis or steatohepatitis as histological lesions may have burned out. 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 (e.g. ultrasound, CT scan or MRI)
within 6 months prior to randomization. If no such imaging result is
available, then it should be performed as part of standard of care.
6. Patients with diabetes mellitus can be enrolled, if they are adequately controlled on a stable dose or doses of antidiabetic medication(s) for at least 3 months before Screening, and their screening HbA1c is ≤9.5%.
7. Patients on vitamin E or pioglitazone 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.
8. Patients on a statin can be enrolled if they are on a stable regimen for at least 3 months before Screening, and expected to be held stable
during the trial.
9. Is not pregnant and must have 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. If a lactating woman, agrees to discontinue nursing before the start of study treatment and refrain from nursing until 90 days after the last dose of study treatment.
12. If a man, agrees to refrain from sperm donation throughout the study period and for a period of 90 days following the last dose of investigational medicinal product (IMP). Female subjects may not begin a cycle of ova donation or harvest throughout the study period and for a period of 90 days following the last dose of IMP.

Please refer to the protocol for full details.

E.4

Principal exclusion criteria

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.
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 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 drug-induced liver disease
• Alcoholic liver disease
• Autoimmune hepatitis
• Wilson's disease
• Hemochromatosis
• Primary biliary cholangitis
• Primary sclerosing cholangitis
• Genetic hemochromatosis
• History or planned liver transplantation
• 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
• 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
• 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 regimen for at least 3 months prior to Screening, and no
changes in the regimen are anticipated during the 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 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.
15. Has participated in an investigational new drug study within 30 days or 5 half-lives whichever is longer, prior to randomization.
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, 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.
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.
Please refer to the protocol for full details.

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase 2b-Phase 3

E.5.2

Secondary end point(s)

Key Secondary Efficacy Endpoint
Incidence rate of patients in the belapectin
treatment groups, compared to placebo, who
develop any of the following: 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

E.5.2.1

Timepoint(s) of evaluation of this end point

Phase 2b-Phase 3

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Seamless, Adaptive

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Chile

Australia

Brazil

Canada

Israel

Korea, Republic of

Mexico

United Kingdom

United States

Belgium

France

Germany

Poland

Spain

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

316

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

102

F.4.2.2

In the whole clinical trial

395

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-10-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-10-13

P. End of Trial
P.	End of Trial Status	Ongoing

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