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

NCT02462967 | Completed Phase 2 Results DMC

• 1 other identifier: GT-026
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 46

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.

Conditions

Hypertension, Portal

Keywords

Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Change in Portal Pressure at Year 1 (Change in HVPG From Baseline and 1 Year)

  Change in Portal Pressure at Year 1 from Baseline

  1 year

Secondary Outcomes (6)

• The Baseline-adjusted Mean Change in the Collagen Proportional Area (%), CPA

  1 year

• 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 Baseline-adjusted Mean Change in Liver Stiffness

  14 to 28 days after final infusion

• The Baseline-adjusted Mean Change in Methacetin Breath Test (MBT), Measured in Percentage

  14 to 28 days after final infusion

• 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

Study Arms (3)

2 mg/kg GR MD 02

ACTIVE COMPARATOR

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

8 mg/kg GR MD 02

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Phosphate buffered saline solution administered every other week over a 52 week period for a total of 26 infusions

Drug: Placebo

Interventions

GR-MD-02 DRUG

GR MD 02 (galactoarabino rhamnogalacturonate), a complex carbohydrate drug that binds to galectin 3

Also known as: galactoarabino rhamnogalacturonate

2 mg/kg GR MD 02; 8 mg/kg GR MD 02

Placebo DRUG

Placebo for GR-MD-02

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a HVPG measurement ≥6 mm Hg.
• 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).
• Is ≥18 years of age and ≤75 years of age at the time of screening.
• 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.
• Is willing and able to provide written informed consent prior to the initiation of any study specific procedures.
• Is not pregnant and must have a negative serum pregnancy test result prior to randomization.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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).
• 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).
• Has had a prior transjugular porto systemic shunt procedure.
• 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.
• 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
• Has a Model End-Stage Liver Disease (MELD) score ≥15 or Child Turcotte Pugh Class B or C.

Sponsors & Collaborators

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

Study Sites (46)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Diego Medical Center

San Diego, California, 92103, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Florida Digestive Health Specialist

Lakewood Rch, Florida, 34211, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

IMIC

Palmetto Bay, Florida, 33157, United States

Location

Tampa General Medical Group

Tampa, Florida, 33606, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Feinberg School of Medicine, Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Minnesota Gastroenterology PA

Saint Paul, Minnesota, 55114, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Kansas City VA Medical Center

Kansas City, Missouri, 64128, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Digestive Health Specialists

Winston-Salem, North Carolina, 27103, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Hospital of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University Gastroenterology

Providence, Rhode Island, 02905, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212-1610, United States

Location

Texas Clinical Research Institute LLC

Arlington, Texas, 76012, United States

Location

Texas Digestive Research Center

Dallas, Texas, 75246, United States

Location

San Antonio Military Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

St Luke's Episcopal Hospital

Houston, Texas, 77030, United States

Location

Pinnacle Clinical Research, PLLC

Live Oak, Texas, 78233, United States

Location

Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Mary Immaculate Hospital

Newport News, Virginia, 23602, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Bon Secours St. Mary's Hospital of Richmond

Richmond, Virginia, 23226, United States

Location

Mcguire Veterans Affairs Medical Center

Richmond, Virginia, 23249, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• Chalasani N, Abdelmalek MF, Garcia-Tsao G, Vuppalanchi R, Alkhouri N, Rinella M, Noureddin M, Pyko M, Shiffman M, Sanyal A, Allgood A, Shlevin H, Horton R, Zomer E, Irish W, Goodman Z, Harrison SA, Traber PG; Belapectin (GR-MD-02) Study Investigators. Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension. Gastroenterology. 2020 Apr;158(5):1334-1345.e5. doi: 10.1053/j.gastro.2019.11.296. Epub 2019 Dec 5.

  PMID: 31812510 RESULT

• Are VS, Vuppalanchi R, Vilar-Gomez E, Chalasani N. Enhanced Liver Fibrosis Score Can Be Used to Predict Liver-Related Events in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1292-1293.e3. doi: 10.1016/j.cgh.2020.06.070. Epub 2020 Jul 3.

  PMID: 32629127 DERIVED

MeSH Terms

Conditions

Hypertension, Portal; Liver Cirrhosis

Interventions

belapectin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Vice President of Regulatory Affairs
• Organization: Galectin Therapeutics

horton@galectintherapeutics.com

678-620-3186

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2015
• First Posted: June 4, 2015
• Study Start: June 1, 2015
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: October 8, 2020
• Results First Posted: October 8, 2020

Record last verified: 2020-10

Locations

US (46)