NASH-CX: Clinical Trial to Evaluation the Safety and Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis and Resultant Portal Hypertension in Patients With Nash Cirrhosis

• Sponsor: Galectin Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02462967
• Collaborator: Dr. Naga Chalasani, MD, Indiana University (Other), Dr. Stephen A. Harrison, MD, Brooke Army Medical Center (Other)
• Enrollment: 162
• Locations: 46
• Arms: 3
• Duration (Months): 28
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Study GT 026 is a Phase 2, multicenter, parallel group, North American, randomized, placebo controlled, double blind study. This study will enroll subjects with portal hypertension (HVPG greater than or equal to 6 mm Hg) who also have a liver biopsy with cirrhosis (Ishak stage 5 or 6), presumably due to NASH, excluding subjects with medium and large varices and those with decompensated cirrhosis.

Subjects with portal hypertension and cirrhosis will be randomly assigned (1:1:1 ratio) to receive 1 of 3 treatment assignments including placebo, GR MD 02 in a dose of 2 mg/kg lean body mass, or GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 intravenous infusions. The primary endpoint analysis is the baseline adjusted change in HVPG at 1 year (53 55 weeks) in subjects treated with placebo as compared to subjects treated with GR MD 02 (2 mg/kg/week or 8 mg/kg/week).

An esophagogastroduodenoscopy (EGD) with evaluation for varices, HVPG, and liver biopsy will be performed before the first infusion and after the final 26th dose of the investigational medicinal product (IMP). Additionally, subjects will undergo a FibroScan (if available) prior to the first infusion, at Infusion Visit 13, and 14 to 28 days following final 26th infusion, an methacetin breath test (MBT), will be performed if available at screening, at Infusion Visit 13, and 14 to 28 days after the final infusion, and blood will be collected for assessment of biomarkers.

All subjects are to attend 2 postdose visits: the first will occur 14 to 28 days after the final dose administration and a second will occur 14 days following the first postdose visit.

Subjects will be offered enrollment into a subsequent separate study, an open label extension study, if there is adequate tolerability and no safety issues or signs of clinical progression that would recommend discontinuation.

Subjects who do not enroll in the open label extension study will be contacted via telephone every 6 months for 2 years and annually thereafter for a total of 4 years.

Condition or Disease	Intervention/Treatment	Phase
Hypertension, Portal	Drug: GR-MD-02; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 162 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Placebo-controlled, Double-blind, Parallel-group, Phase 2 Clinical Trial to Evaluation the Safety and Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis and Resultant Portal Hypertension in Patients With Nash Cirrhosis
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 2 mg/kg GR MD 02 GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions	Drug: GR-MD-02; GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3; Other Names: galactoarabino rhamnogalacturonate
Active Comparator: 8 mg/kg GR MD 02 GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions	Drug: GR-MD-02; GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3; Other Names: galactoarabino rhamnogalacturonate
Placebo Comparator: Placebo Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions	Drug: Placebo; Placebo for GR-MD-02

Outcome Measures

Primary Outcome Measures

1. Change in Portal Pressure at Year 1 (Change in HVPG From Baseline and 1 Year) [1 year]

   Change in Portal Pressure at Year 1 from Baseline

Secondary Outcome Measures

1. The Baseline-adjusted Mean Change in the Collagen Proportional Area (%), CPA [1 year]

   The baseline-adjusted mean change in the CPA at 1 year as determined by digital morphometric analysis of liver biopsies. Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with liver disease and can sub-classify cirrhosis.

2. The Number (Percentage) of Subjects Who Have at Least a One Stage Change in Ishak Assessment From Liver Biology Histopathology. Histopathological Staging of Fibrosis [1 year]

   The number (percentage) of subjects who have at least a one stage change in Ishak histopathological staging of fibrosis at 1 year as assessed on liver biopsy. Liver biopsy is the accepted standard for histologic assessment of liver disease activity and fibrosis. Ishak assessments on liver biopsy range from 0=no fibrosis to 6=cirrhosis.

3. The Baseline-adjusted Mean Change in Liver Stiffness [14 to 28 days after final infusion]

   The baseline-adjusted mean change in liver stiffness as determined by FibroScan score 14 to 28 days after final infusion. FibroScan is a device that measures scarring by measuring the stiffness of your liver.The fibrosis result is measured in kilopascals (kPa) It's normally between 2 and 6 kPa. The highest possible result is 75 kPa. Many people with liver disease(s) have a result that's higher than the normal range.

4. The Baseline-adjusted Mean Change in Methacetin Breath Test (MBT), Measured in Percentage [14 to 28 days after final infusion]

   The baseline-adjusted mean change in the metabolic capacity of the liver as determined the methacetin breath test (MBT) at 14 to 28 days after final infusion. The results obtained from the MBT medical device are expressed as delta over baseline (DOB), which expresses the change in 13CO2/12CO2 ratio in comparison to the baseline measurement. It can be transformed into the percentage of 13C dose recovered over time (PDR) after the ingestion of Methacetin, and the cumulative PDR (CPDR), the rate at which 13C substrate is metabolized, derived from the breath 13C/12C ratio.

5. The Number (Percentage) of Subjects Who Have at Least a One Stage Change in Brunt-Kleiner Assessment on Liver Biopsy Histopathological Staging of Fibrosis [1 year]

   The number (percentage) of subjects who have at least a one stage change in Brunt-Kleiner histopathological staging of fibrosis at 1 year as assessed on liver biopsy. Liver biopsy is the accepted standard for histologic assessment of liver disease activity and fibrosis. Brunt-Kleiner assessments on liver biopsy range from 0 (absent) to 4 (cirrhosis).

6. The Number (Percentage) of Subjects That Develop a Clinical Complication of Cirrhosis [1 year]

   The number (percentage) of subjects with progression of cirrhosis at 1 year, defined as the development of any of the following clinical complications: esophageal variceal hemorrhage or portal hypertensive gastropathy hemorrhage (confirmed by endoscopy or interventional radiology); clinically apparent ascites; spontaneous bacterial peritonitis; overt hepatic encephalopathy; an increase in Child-Turcotte-Pugh score ≥2 points; newly diagnosed varices in a subject without prior varices; progression from small to medium or large varices; qualification for liver transplant defined as a Model for End-Stage Liver Disease (MELD) score ≥15; listing for a liver transplant or the performance of a liver transplant; liver-related mortality

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Has a HVPG measurement ≥6 mm Hg.

2. Has a liver biopsy with cirrhosis (Ishak stage 5 or 6) presumably due to NASH. A liver biopsy diagnosis of cirrhosis presumably due to NASH will include the following 3 categories:

• Cirrhosis with a definitive pathological diagnosis of NASH (presence of fat, ballooning degeneration, and inflammation);

• Cirrhosis wherein the biopsy contains either fat (>5%) or ballooning hepatocytes with no evidence of viral hepatitis or other liver disease; or

• Cirrhosis with no evidence of viral hepatitis or other liver disease in a subject with at least a 5 year history of obesity (BMI ≥30) or at least a 5 year history of diabetes mellitus (as defined by diagnosis by a physician and treatment with at least 1 antidiabetic medication).

1. Is ≥18 years of age and ≤75 years of age at the time of screening.

2. Absence of hepatocellular carcinoma by valid imaging (liver ultrasound, triple phase computed tomography of liver or magnetic resonance imaging of liver) within 6 months prior to randomization. If there is not such test available, then it should be performed as part of standard of care.

3. Is willing and able to provide written informed consent prior to the initiation of any study specific procedures.

4. Is not pregnant and must have a negative serum pregnancy test result prior to randomization.

5. 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).

• Effective forms of contraception include condom, hormonal methods (birth control pills, injections or implants), diaphragm, cervical cap, or intrauterine device throughout his/her participation in this study and for 90 days after discontinuation of study treatment. Surgically sterile males and females are not required to use contraception provided they have been considered surgically sterile for at least 6 months. Surgical sterility includes history of vasectomy, hysterectomy, bilateral salpingo oophorectomy, or bilateral tubal ligation. Postmenopausal women who have been amenorrheic for at least 2 years at the time of screening will be considered sterile.

1. 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.

2. 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 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.

3. Prior to randomization, any subject on statins, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, or β 1 selective adrenergic receptor inhibitors should have been on a stable dose for at least 2 months and all attempts should be made to continue the subject on the same dose of the medication for the duration of study participation.

Exclusion Criteria:

1. Has a history of hepatic decompensation including any episode of variceal bleeding, ascites not controlled by medication, or overt hepatic encephalopathy (defined by the clinical judgment of the principal investigator but shall include the presence of lethargy, disorientation, inappropriate behavior, and the presence of asterixis).

2. Has a presence of medium or large varices or varices with red signs regardless of size based on endoscopy.

• Small varices are defined by veins that occupy <25% of the distal one third of the esophageal lumen when insufflated. Veins that completely flatten upon insufflation of the esophagus are not conserved varices. Any varices larger than that are medium (up to 50%) or large (>50%).

• Red signs include red wale markings (dilated venules oriented longitudinally on the variceal surface), cherry red spots (small, red, spotty dilated venules usually approximately 2 mm in diameter on the variceal surface) or hematocystic spots (large, round, crimson red projection >3 mm that look like a blood blister on the variceal surface).

1. Has had a prior transjugular porto systemic shunt procedure.

2. Has evidence of other forms of chronic liver disease including viral hepatitis B or C, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, alpha 1 antitrypsin deficiency, alcoholic hepatitis, hemochromatosis, liver cancer, history of biliary diversion, or autoimmune hepatitis.

3. Has any of the following laboratory values:

• Serum alanine aminotransferase levels >10 × the upper limits of normal

• Serum aspartate aminotransferase levels >10 × the upper limits of normal

• Platelet count <60 000/mm3

*. Serum albumin ≤2.8 g/dL

• International normalized ratio (INR) ≥1.7

• Direct bilirubin ≥2.0 mg/dL

• Alpha fetoprotein >200 ng/mL

1. Has a Model End-Stage Liver Disease (MELD) score ≥15 or Child Turcotte Pugh Class B or

1. Has an estimated creatinine clearance of <50 mL/minute. Glomerular filtration rate will be estimated using the Cockcroft-Gault equation (Cockcroft 1976):

• Males: CrCl (mL/min) = ([140 - age] × weight) / (SCr × 72)

• Females: CrCl (mL/min) = ([140 - age]) × weight) / (SCr × 72)] × 0.85

• Where CrCl is creatinine clearance, age is in years, weight is in kg, and SCr is serum creatinine in mg/dL

1. Is unwilling or unable to safely undergo HVPG or liver biopsy.

2. Has known positivity for human immunodeficiency virus (HIV) infection or a positive HIV test result at screening.

3. Has had major surgery within 8 weeks of randomization, significant traumatic injury within 6 months, or anticipation of need for major surgical procedure during the course of the study.

4. Has a history of a solid organ transplant requiring current immunosuppression therapy.

5. Has used nonselective β adrenergic inhibitors within 6 weeks prior to randomization.

6. Has planned or anticipated variceal ligation therapy during the study.

7. Has had weight reduction surgery within the past 3 years or plans to undergo weight reduction surgery during the study.

8. Has current, significant alcohol consumption or a history of significant alcohol consumption for a period of more than 3 consecutive months any time within 1 year prior to screening.

• Significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males. On average, a standard drink in the United States is considered to be 14 grams of alcohol, equivalent to 12 fluid ounces of regular beer (5% alcohol), 5 fluid ounces of table wine (12% alcohol), or 1.5 fluid ounces of 80 proof spirits (40% alcohol).

A score of ≥8 on the Alcohol Use Disorders Identification Test (AUDIT) (Babor 2000) will result in exclusion.

1. Has a positive urine screen result for amphetamines, cocaine, or nonprescription opiates (heroin, morphine) at screening.

2. Has clinically significant and uncontrolled 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 devise/ablation or Grade II or greater peripheral vascular disease within 12 months prior to randomization.

3. 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.

4. Has concurrent infection including diagnoses of fever of unknown origin at the time of randomization.

5. Has a history of malignancy, except for the following: adequately treated nonmetastatic basal cell skin cancer; any other type of skin cancer, except melanoma, that has been adequately treated and has not recurred for at least 1 year prior to enrollment; and adequately treated in situ cervical cancer that has not recurred for at least 1 year prior to screening.

6. Participates in an investigational new drug study within 30 days prior to randomization (including follow up visits) or at any time during the current study.

7. Has a clinically significant medical or psychiatric condition considered high risk for participation in an investigational study.

8. Fails to give informed consent.

9. Has known allergies to the IMP or any of its excipients.

10. Has previously received GR-MD-02 within 6 months of randomization.

11. Is an employee or family member of the investigator or study center personnel.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
2	University of California Davis Medical Center	Sacramento	California	United States	95817
3	University of California San Diego Medical Center	San Diego	California	United States	92103
4	University of Colorado Denver	Aurora	Colorado	United States	80045
5	University of Florida	Gainesville	Florida	United States	32610
6	Florida Digestive Health Specialist	Lakewood Ranch	Florida	United States	34211
7	University of Miami	Miami	Florida	United States	33136
8	IMIC	Palmetto Bay	Florida	United States	33157
9	Tampa General Medical Group	Tampa	Florida	United States	33606
10	Piedmont Hospital	Atlanta	Georgia	United States	30309
11	Feinberg School of Medicine, Northwestern University	Chicago	Illinois	United States	60611
12	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
13	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
14	Mercy Medical Center	Baltimore	Maryland	United States	21202
15	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
16	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
17	University of Michigan	Ann Arbor	Michigan	United States	48109
18	Henry Ford Health System	Detroit	Michigan	United States	48202
19	Minnesota Gastroenterology PA	Saint Paul	Minnesota	United States	55114
20	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
21	Kansas City VA Medical Center	Kansas City	Missouri	United States	64128
22	Saint Louis University	Saint Louis	Missouri	United States	63104
23	North Shore University Hospital	Manhasset	New York	United States	11030
24	Columbia University Medical Center	New York	New York	United States	10032
25	Duke University Medical Center	Durham	North Carolina	United States	27710
26	Digestive Health Specialists	Winston-Salem	North Carolina	United States	27103
27	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
28	Hospital of The University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
29	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
30	University Gastroenterology	Providence	Rhode Island	United States	02905
31	Medical University of South Carolina	Charleston	South Carolina	United States	29403
32	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212-1610
33	Texas Clinical Research Institute LLC	Arlington	Texas	United States	76012
34	Texas Digestive Research Center	Dallas	Texas	United States	75246
35	San Antonio Military Medical Center	Fort Sam Houston	Texas	United States	78234
36	St Luke's Episcopal Hospital	Houston	Texas	United States	77030
37	Pinnacle Clinical Research, PLLC	Live Oak	Texas	United States	78233
38	Texas Liver Institute	San Antonio	Texas	United States	78215
39	Intermountain Medical Center	Murray	Utah	United States	84107
40	Mary Immaculate Hospital	Newport News	Virginia	United States	23602
41	Digestive and Liver Disease Specialists	Norfolk	Virginia	United States	23502
42	Bon Secours St. Mary's Hospital of Richmond	Richmond	Virginia	United States	23226
43	Mcguire Veterans Affairs Medical Center	Richmond	Virginia	United States	23249
44	Virginia Commonwealth University	Richmond	Virginia	United States	23298
45	Swedish Medical Center	Seattle	Washington	United States	98104
46	University of Washington	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Galectin Therapeutics Inc.
• Dr. Naga Chalasani, MD, Indiana University
• Dr. Stephen A. Harrison, MD, Brooke Army Medical Center

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 20, 2015
• Statistical Analysis Plan - Jan 26, 2018

More Information

Publications

None provided.

• Responsible Party: Galectin Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT02462967
• Other Study ID Numbers: GT-026
• First Posted: Jun 4, 2015
• Last Update Posted: Oct 8, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Galectin Therapeutics Inc.: Liver Cirrhosis
• Additional relevant MeSH terms: Liver Cirrhosis; Hypertension, Portal; Hypertension; Fibrosis

Study Results

Participant Flow

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
Period Title: Overall Study
STARTED	54	54	54
COMPLETED	52	48	51
NOT COMPLETED	2	6	3

Baseline Characteristics

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo	Total
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02	Total of all reporting groups
Overall Participants	54	54	54	162
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (7.54)	57.1 (9.30)	58.4 (8.51)	58.3 (8.47)
Sex: Female, Male (Count of Participants)
Female	34 63%	43 79.6%	36 66.7%	113 69.8%
Male	20 37%	11 20.4%	18 33.3%	49 30.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 13%	13 24.1%	8 14.8%	28 17.3%
Not Hispanic or Latino	47 87%	41 75.9%	46 85.2%	134 82.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 1.9%	0 0%	0 0%	1 0.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.9%	0 0%	1 0.6%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	53 98.1%	52 96.3%	54 100%	159 98.1%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 1.9%	0 0%	1 0.6%
Region of Enrollment (participants) [Number]
United States	54 100%	54 100%	54 100%	162 100%
Portal Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	12.36 (4.288)	12.72 (4.203)	11.59 (3.994)	12.22 (4.162)

Outcome Measures

1. Primary Outcome

Title	Change in Portal Pressure at Year 1 (Change in HVPG From Baseline and 1 Year)
Description	Change in Portal Pressure at Year 1 from Baseline
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The analysis is performed with the Full Analysis Set (FAS) in accordance with the Protocol and the Statistical Analysis Plan (SAP). The criteria for the Full Analysis Set is specified in the SAP and resulted in the Overall Number of Participants Analyzed being less than the numbers in the Participant Flow module.

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
Measure Participants	48	45	50
Mean (Standard Deviation) [mm HG]	-0.39 (4.018)	-0.24 (3.100)	0.19 (3.240)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	The Baseline-adjusted Mean Change in the Collagen Proportional Area (%), CPA
Description	The baseline-adjusted mean change in the CPA at 1 year as determined by digital morphometric analysis of liver biopsies. Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with liver disease and can sub-classify cirrhosis.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
Measure Participants	46	41	45
Mean (Standard Deviation) [Percent Area (%)]	1.2 (5.54)	0.1 (5.68)	1.3 (8.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.447
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.921
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	The Number (Percentage) of Subjects Who Have at Least a One Stage Change in Ishak Assessment From Liver Biology Histopathology. Histopathological Staging of Fibrosis
Description	The number (percentage) of subjects who have at least a one stage change in Ishak histopathological staging of fibrosis at 1 year as assessed on liver biopsy. Liver biopsy is the accepted standard for histologic assessment of liver disease activity and fibrosis. Ishak assessments on liver biopsy range from 0=no fibrosis to 6=cirrhosis.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
Measure Participants	54	54	54
Count of Participants [Participants]	17 31.5%	13 24.1%	14 25.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.522
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	The Baseline-adjusted Mean Change in Liver Stiffness
Description	The baseline-adjusted mean change in liver stiffness as determined by FibroScan score 14 to 28 days after final infusion. FibroScan is a device that measures scarring by measuring the stiffness of your liver.The fibrosis result is measured in kilopascals (kPa) It's normally between 2 and 6 kPa. The highest possible result is 75 kPa. Many people with liver disease(s) have a result that's higher than the normal range.
Time Frame	14 to 28 days after final infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
Measure Participants	54	54	54
Mean (Standard Deviation) [Kilopascals, kPa]	-0.59 (2.00)	-2.76 (2.02)	-0.79 (2.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.943
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.492
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	The Baseline-adjusted Mean Change in Methacetin Breath Test (MBT), Measured in Percentage
Description	The baseline-adjusted mean change in the metabolic capacity of the liver as determined the methacetin breath test (MBT) at 14 to 28 days after final infusion. The results obtained from the MBT medical device are expressed as delta over baseline (DOB), which expresses the change in 13CO2/12CO2 ratio in comparison to the baseline measurement. It can be transformed into the percentage of 13C dose recovered over time (PDR) after the ingestion of Methacetin, and the cumulative PDR (CPDR), the rate at which 13C substrate is metabolized, derived from the breath 13C/12C ratio.
Time Frame	14 to 28 days after final infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
Measure Participants	54	54	54
Mean (Standard Deviation) [percent]	-40.51 (34.45)	-20.57 (38.00)	-51.00 (35.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.558
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	The Number (Percentage) of Subjects Who Have at Least a One Stage Change in Brunt-Kleiner Assessment on Liver Biopsy Histopathological Staging of Fibrosis
Description	The number (percentage) of subjects who have at least a one stage change in Brunt-Kleiner histopathological staging of fibrosis at 1 year as assessed on liver biopsy. Liver biopsy is the accepted standard for histologic assessment of liver disease activity and fibrosis. Brunt-Kleiner assessments on liver biopsy range from 0 (absent) to 4 (cirrhosis).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
Measure Participants	54	54	54
Count of Participants [Participants]	3 5.6%	2 3.7%	1 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.362
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.602
	Comments
	Method	ANCOVA
	Comments

7. Secondary Outcome

Title	The Number (Percentage) of Subjects That Develop a Clinical Complication of Cirrhosis
Description	The number (percentage) of subjects with progression of cirrhosis at 1 year, defined as the development of any of the following clinical complications: esophageal variceal hemorrhage or portal hypertensive gastropathy hemorrhage (confirmed by endoscopy or interventional radiology); clinically apparent ascites; spontaneous bacterial peritonitis; overt hepatic encephalopathy; an increase in Child-Turcotte-Pugh score ≥2 points; newly diagnosed varices in a subject without prior varices; progression from small to medium or large varices; qualification for liver transplant defined as a Model for End-Stage Liver Disease (MELD) score ≥15; listing for a liver transplant or the performance of a liver transplant; liver-related mortality
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/kg GR MD 02	8 mg/kg GR MD 02	Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3	Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
Measure Participants	54	54	54
Count of Participants [Participants]	10 18.5%	11 20.4%	12 22.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.633
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg GR MD 02, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.814
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	1 year
Arm/Group Title	2 mg/kg GR MD 02		8 mg/kg GR MD 02		Placebo
Arm/Group Description	GR MD 02 in a dose of 2 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3		GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 infusions GR-MD-02: GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3		Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions Placebo: Placebo for GR-MD-02
All Cause Mortality
	2 mg/kg GR MD 02		8 mg/kg GR MD 02		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/53 (1.9%)		0/54 (0%)		0/54 (0%)
Serious Adverse Events
	2 mg/kg GR MD 02		8 mg/kg GR MD 02		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/53 (18.9%)		16/54 (29.6%)		12/54 (22.2%)
Blood and lymphatic system disorders
ANAEMIA	0/53 (0%)	0	1/54 (1.9%)	1	2/54 (3.7%)	2
Cardiac disorders
SUPRAVENTRICULAR TACHYCARDIA	0/53 (0%)	0	2/54 (3.7%)	2	0/54 (0%)	0
ARTERIOSCLEROSIS CORONARY ARTERY	1/53 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
ATRIAL FIBRILLATION	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
CARDIAC FAILURE CONGESTIVE	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
Gastrointestinal disorders
ABDOMINAL PAIN	2/53 (3.8%)	2	0/54 (0%)	0	1/54 (1.9%)	1
HAEMATEMESIS	1/53 (1.9%)	1	1/54 (1.9%)	1	0/54 (0%)	0
DIARRHOEA	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
GASTROINTESTINAL HAEMORRHAGE	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
HAEMATOCHEZIA	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
OESOPHAGEAL HAEMORRHAGE	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
PANCREATITIS ACUTE	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
SMALL INTESTINAL OBSTRUCTION	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
General disorders
HERNIA PAIN	1/53 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
NON-CARDIAC CHEST PAIN	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
PYREXIA	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
Infections and infestations
SEPSIS	0/53 (0%)	0	2/54 (3.7%)	2	0/54 (0%)	0
ABSCESS OF EYELID	1/53 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
CELLULITIS	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
ESCHERICHIA BACTERAEMIA	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
GASTROENTERITIS SALMONELLA	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
PNEUMONIA	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
Injury, poisoning and procedural complications
DURAL TEAR	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
STOMA COMPLICATION	1/53 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
Metabolism and nutrition disorders
HYPONATRAEMIA	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/53 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
OSTEOARTHRITIS	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA OF SKIN	1/53 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
Nervous system disorders
HYPOAESTHESIA	0/53 (0%)	0	0/54 (0%)	0	1/54 (1.9%)	1
TRANSIENT ISCHAEMIC ATTACK	0/53 (0%)	0	1/54 (1.9%)	1	0/54 (0%)	0
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM	1/53 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
Other (Not Including Serious) Adverse Events
	2 mg/kg GR MD 02		8 mg/kg GR MD 02		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/53 (98.1%)		48/54 (88.9%)		53/54 (98.1%)
Eye disorders
Abdominal pain	5/53 (9.4%)	5	3/54 (5.6%)	3	7/54 (13%)	7
Gastrointestinal disorders
Nausea	14/53 (26.4%)	14	8/54 (14.8%)	8	11/54 (20.4%)	11
Diarrhoea	12/53 (22.6%)	12	8/54 (14.8%)	8	11/54 (20.4%)	11
Abdominal pain upper	8/53 (15.1%)	8	8/54 (14.8%)	8	13/54 (24.1%)	13
Vomiting	7/53 (13.2%)	7	7/54 (13%)	7	2/54 (3.7%)	2
General disorders
Fatigue	9/53 (17%)	9	9/54 (16.7%)	9	10/54 (18.5%)	10
Oedema peripheral	8/53 (15.1%)	8	4/54 (7.4%)	4	7/54 (13%)	7
Infections and infestations
Nasopharyngitis	14/53 (26.4%)	14	5/54 (9.3%)	5	8/54 (14.8%)	8
Urinary tract infection	8/53 (15.1%)	8	6/54 (11.1%)	6	9/54 (16.7%)	9
Sinusitis	6/53 (11.3%)	6	7/54 (13%)	7	4/54 (7.4%)	4
Upper respiratory tract infection	8/53 (15.1%)	8	4/54 (7.4%)	4	5/54 (9.3%)	5
Bronchitis	7/53 (13.2%)	7	3/54 (5.6%)	3	5/54 (9.3%)	5
Injury, poisoning and procedural complications
Contusion	10/53 (18.9%)	10	3/54 (5.6%)	3	6/54 (11.1%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	6/53 (11.3%)	6	9/54 (16.7%)	9	1/54 (1.9%)	1
Muscle spasms	8/53 (15.1%)	8	3/54 (5.6%)	3	4/54 (7.4%)	4
Pain in extremity	4/53 (7.5%)	4	4/54 (7.4%)	4	6/54 (11.1%)	6
Back pain	3/53 (5.7%)	3	7/54 (13%)	7	2/54 (3.7%)	2
Nervous system disorders
Headache	9/53 (17%)	9	6/54 (11.1%)	6	9/54 (16.7%)	9
Dizziness	2/53 (3.8%)	2	5/54 (9.3%)	5	9/54 (16.7%)	9
Skin and subcutaneous tissue disorders
Rash	5/53 (9.4%)	5	5/54 (9.3%)	5	6/54 (11.1%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.