NASH-FX: Clinical Trial to Evaluate Efficacy of GR-MD-02 for Treatment of Liver Fibrosis in Patients With NASH With Advanced Fibrosis

• Sponsor: Galectin Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02421094
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Actual Duration (Months): 12.9
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

A Randomized, Controlled, Double-blind, Parallel Group, Single Center Phase 2 Clinical Trial to Evaluate Multiple Non-Invasive Liver Fibrosis Imaging Methods in the Assessment of the Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis in Patients with NASH with Advanced Fibrosis

Condition or Disease	Intervention/Treatment	Phase
Nonalcoholic Steatohepatitis	Drug: GR-MD-02; Drug: Placebo	Phase 2

Detailed Description

The primary objective is to determine the difference between placebo and GR-MD-02 treatment in the baseline adjusted mean change in liver fibrosis as measured by corrected T1 (cT1) mapping as determined from LiverMultiScan (LMS), a multi-parametric MRI protocol.

Secondary objectives include evaluating differences between subjects treated with GR-MD-02 versus placebo in:

• The baseline-adjusted change in liver stiffness as measured by MR-elastography

• The baseline-adjusted change in liver stiffness as measured by FibroScan® scores.

An exploratory objective will be to evaluate the correlation of the three diagnostic modalities of LiverMultiScan, MR-Elastography, and FibroScan®.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study to Evaluate Non-Invasive Imaging Methods in Efficacy Assessment of GR-MD-02 for the Treatment of Liver Fibrosis in Patients With NASH With Advanced Fibrosis
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Sep 27, 2016
• Actual Study Completion Date: Sep 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: GR-MD-02 Active	Drug: GR-MD-02; GM-MD-02 active; Other Names: galactoarabino-rhamnogalacturonate
Placebo Comparator: Placebo Placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Mean Change in Liver Fibrosis of Corrected T1 (cT1) Mapping (LiverMultiScan -LMS) [16 weeks]

   Difference in baseline adjusted mean change in liver fibrosis of corrected T1 (cT1) mapping with LiverMultiScan (LMS). LiverMultiScan is CE marked as a class IIa medical device. Corrected T1 (cT1) is a Magnetic Resonance (MR) relaxation parameter/measure from the device.The measure cT1 can be compared across different Magnetic Resonance Imaging (MRI) systems and sites. It is an emerging biomarker for rapid quantification of hepatic fibro-inflammatory disease. In unhealthy tissue, such as in inflamed and fibrotic tissues, measures result in longer cT1-relaxation.

Secondary Outcome Measures

1. Baseline-adjusted Change in Liver Stiffness With MR-elastography (MRE) [16 weeks]

   Baseline-adjusted change in liver stiffness as measured by MR-elastography. Magnetic resonance elastography (MRE) is a technology that uses MRI imaging with low-frequency vibrations to create a visual map (elastogram) that shows stiffness of body tissues. Currently, MRE is used to detect stiffening of the liver caused by fibrosis and inflammation in chronic liver disease. Liver stiffness increases with liver damage/disease.

2. Baseline-adjusted Change in Liver Stiffness by FibroScan® [16 weeks]

   Baseline-adjusted change in liver stiffness as measured by FibroScan® scores. FibroScan 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. Many people with liver disease(s) have a result that's higher than the normal range.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects must have liver biopsy demonstrating NASH with Brunt Stage 3 fibrosis within 12 months of randomization. The subject is ≥ 18 years of age and ≤ 75 years old at the time of screening

• The subject is willing and able to provide written informed consent

• The subject is not pregnant and must have a negative pregnancy test prior to start of the study. Post-menopausal women must have been amenorrheic for at least 12 months to be considered of non-child-bearing potential.

• Fertile men and women participating in heterosexual relations must agree to use effective means of contraception throughout their participation in this study and for 90 days after discontinuation of study medication.

• Lactating females must agree to discontinue nursing before the start of study treatment and refrain from nursing until 90 days after discontinuation of study medication.

• Male subjects must refrain from sperm donation throughout the study period and for a period of 90 days following the last dose of study drug.

Exclusion Criteria:

• A history of hepatic decompensation including any episode of variceal bleeding, clinically detectable ascites, or overt hepatic encephalopathy.

• Status post TIPS (Transjugular Intrahepatic Porto-systemic Shunt) procedure.

• 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, or history of biliary diversion.

• Any of the following laboratory values: Serum alanine aminotransferase (ALT) and aspartate aminotransferase levels > 10X upper limits of normal, Serum creatinine ≥ 2.0 mg/dL, Platelet count < 60,000/mm3, Serum albumin ≤ 2.8 g/dL, INR ≥ 1.7, Direct bilirubin ≥ 2.0 mg/dL

• A MELD score ≥ 15 or Child-Pugh-Turcotte Stage B or C

• Known positivity for Human Immunodeficiency Virus (HIV) infection

• Any subject who had major surgery within 8 weeks of Day 1, significant traumatic injury, or anticipation of need for major surgical procedure during the course of the study.

• Weight reduction surgery within the past 3 years.

• Any subject with 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 will be excluded.

• Any subject with concurrent infection including diagnoses of fever of unknown origin (FUO) (subjects must be afebrile at the start of therapy).

• Any history of malignancy, except for the following adequately-treated non metastatic 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 enrollment.

• Participation in an investigational new drug (IND) trial in the 30 days before randomization

• Clinically significant medical or psychiatric condition considered a high risk for participation in an investigational study.

• Failure to give informed consent

• Subjects with known allergies to the study drug or any of its excipients.

• Is an employee or family member of the investigator or study site personnel.

• Any subject who cannot undergo an MRI, e.g., due to certain metal or electronic device implants, as determined by the Principal Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234

Sponsors and Collaborators

• Galectin Therapeutics Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Galectin Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT02421094
• Other Study ID Numbers: GT-028
• First Posted: Apr 20, 2015
• Last Update Posted: Oct 8, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Fibrosis

Study Results

Participant Flow

Arm/Group Title	GR-MD-02 8 mg/kg	Placebo
Arm/Group Description	Active GR-MD-02: GM-MD-02 active	Placebo Placebo: Placebo
Period Title: Overall Study
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	GR-MD-02 8 mg/kg	Placebo	Total
Arm/Group Description	Active GR-MD-02: GM-MD-02 active	Placebo Placebo: Placebo	Total of all reporting groups
Overall Participants	15	15	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.7 (6.19)	56.7 (6.15)	58.2 (6.17)
Sex: Female, Male (Count of Participants)
Female	6 40%	7 46.7%	13 43.3%
Male	9 60%	8 53.3%	17 56.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 46.7%	6 40%	13 43.3%
Not Hispanic or Latino	8 53.3%	9 60%	17 56.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 6.7%	0 0%	1 3.3%
Native Hawaiian or Other Pacific Islander	1 6.7%	0 0%	1 3.3%
Black or African American	0 0%	0 0%	0 0%
White	13 86.7%	15 100%	28 93.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Liver Fibrosis of Corrected T1 (cT1) Mapping (LiverMultiScan -LMS)
Description	Difference in baseline adjusted mean change in liver fibrosis of corrected T1 (cT1) mapping with LiverMultiScan (LMS). LiverMultiScan is CE marked as a class IIa medical device. Corrected T1 (cT1) is a Magnetic Resonance (MR) relaxation parameter/measure from the device.The measure cT1 can be compared across different Magnetic Resonance Imaging (MRI) systems and sites. It is an emerging biomarker for rapid quantification of hepatic fibro-inflammatory disease. In unhealthy tissue, such as in inflamed and fibrotic tissues, measures result in longer cT1-relaxation.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GR-MD-02 8 mg/kg	Placebo
Arm/Group Description	Active GR-MD-02: GM-MD-02 active	Placebo Placebo: Placebo
Measure Participants	15	15
Least Squares Mean (95% Confidence Interval) [milliseconds (ms)]	19.15	1.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GR-MD-02 8 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1621
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Baseline-adjusted Change in Liver Stiffness With MR-elastography (MRE)
Description	Baseline-adjusted change in liver stiffness as measured by MR-elastography. Magnetic resonance elastography (MRE) is a technology that uses MRI imaging with low-frequency vibrations to create a visual map (elastogram) that shows stiffness of body tissues. Currently, MRE is used to detect stiffening of the liver caused by fibrosis and inflammation in chronic liver disease. Liver stiffness increases with liver damage/disease.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GR-MD-02 8 mg/kg	Placebo
Arm/Group Description	Active GR-MD-02: GM-MD-02 active	Placebo Placebo: Placebo
Measure Participants	15	15
Mean (Standard Deviation) [Kilopascals, kPa]	0.17 (0.55)	0.18 (0.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GR-MD-02 8 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9835
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Baseline-adjusted Change in Liver Stiffness by FibroScan®
Description	Baseline-adjusted change in liver stiffness as measured by FibroScan® scores. FibroScan 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. Many people with liver disease(s) have a result that's higher than the normal range.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GR-MD-02 8 mg/kg	Placebo
Arm/Group Description	Active GR-MD-02: GM-MD-02 active	Placebo Placebo: Placebo
Measure Participants	15	15
Mean (Standard Deviation) [Kilopascals, kPa]	1.11 (9.51)	-2.32 (5.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GR-MD-02 8 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2660
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	16 weeks
Arm/Group Title	GR-MD-02 8 mg/kg		Placebo
Arm/Group Description	Active GR-MD-02: GM-MD-02 active		Placebo Placebo: Placebo
All Cause Mortality
	GR-MD-02 8 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	GR-MD-02 8 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	GR-MD-02 8 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/15 (73.3%)		11/15 (73.3%)
Blood and lymphatic system disorders
Lymphadenopathy	2/15 (13.3%)	2	0/15 (0%)	0
Cardiac disorders
Cardiac murmur	1/15 (6.7%)	1	1/15 (6.7%)	1
Gastrointestinal disorders
Abdominal distension	1/15 (6.7%)	1	0/15 (0%)	0
Abdominal pain	0/15 (0%)	0	1/15 (6.7%)	1
Constipation	2/15 (13.3%)	2	1/15 (6.7%)	1
Diarrhoea	4/15 (26.7%)	4	2/15 (13.3%)	2
Haemorrhoids	1/15 (6.7%)	1	0/15 (0%)	0
Nausea	3/15 (20%)	3	1/15 (6.7%)	1
General disorders
Chest pain	1/15 (6.7%)	1	0/15 (0%)	0
Cyst	0/15 (0%)	0	1/15 (6.7%)	1
Oedema peripheral	0/15 (0%)	0	1/15 (6.7%)	1
Food allergy	0/15 (0%)	0	1/15 (6.7%)	1
Infections and infestations
Body tinea	0/15 (0%)	0	1/15 (6.7%)	1
Bronchitis	0/15 (0%)	0	1/15 (6.7%)	1
Diverticulitis	1/15 (6.7%)	1	0/15 (0%)	0
Gastroenteritis viral	0/15 (0%)	0	1/15 (6.7%)	1
Sinusitis	1/15 (6.7%)	1	0/15 (0%)	0
Upper respiratory tract infection	1/15 (6.7%)	1	1/15 (6.7%)	1
Urinary tract infection	1/15 (6.7%)	1	0/15 (0%)	0
Injury, poisoning and procedural complications
Ligament sprain	1/15 (6.7%)	1	1/15 (6.7%)	1
Muscle sprain	1/15 (6.7%)	1	1/15 (6.7%)	1
Procedural pain	0/15 (0%)	0	1/15 (6.7%)	1
Tendon injury	1/15 (6.7%)	1	0/15 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	2/15 (13.3%)	2	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/15 (0%)	0	1/15 (6.7%)	1
Muscle Spasms	1/15 (6.7%)	1	1/15 (6.7%)	1
Myalgia	1/15 (6.7%)	1	0/15 (0%)	0
Nervous system disorders
Dizziness	2/15 (13.3%)	2	0/15 (0%)	0
Headache	1/15 (6.7%)	1	1/15 (6.7%)	1
Lethargy	0/15 (0%)	0	1/15 (6.7%)	1
Tension headache	0/15 (0%)	0	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/15 (6.7%)	1	0/15 (0%)	0
Nasal Congestion	0/15 (0%)	0	1/15 (6.7%)	1
Oropharyngeal pain	1/15 (6.7%)	1	0/15 (0%)	0
Paranasal sinus discomfort	0/15 (0%)	0	1/15 (6.7%)	1
Productive cough	1/15 (6.7%)	1	0/15 (0%)	0
Skin and subcutaneous tissue disorders
Palmar erythematous	0/15 (0%)	0	1/15 (6.7%)	1
Pruritus	1/15 (6.7%)	1	0/15 (0%)	0
Rash Erythematous	1/15 (6.7%)	1	0/15 (0%)	0
Skin exfoliation	0/15 (0%)	0	1/15 (6.7%)	1
Telangiectasia	1/15 (6.7%)	1	2/15 (13.3%)	2

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.