Phase 1 Study to Evaluate Safety of GR-MD-02 in Subjects With Non-Alcoholic Steatohepatitis (NASH) and Advanced Fibrosis

NCT01899859 | Completed Phase 1 DMC

• 1 other identifier: GT-020
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to characterize the safety, tolerability and dose-limiting toxicities (DLTs) for GR-MD-02 when administered intravenously to subjects with biopsy-proven NASH with advanced liver fibrosis.

Conditions

Non-Alcoholic Steatohepatitis (NASH)

Keywords

Non-Alcoholic Steatohepatitis (NASH)

Outcome Measures

Primary Outcomes (1)

• Primary objective is to characterize safety for GR-MD-02 administered intravenously to subjects w/ biopsy-proven NASH w/ advanced liver fibrosis. Specifically assessed by number of subjects experiencing TEAEs.

  The primary objective of this study is to characterize the safety, which includes the tolerability and dose-limiting toxicity (DLT), for GR-MD-02 when administered intravenously to subjects with biopsy-proven NASH with advanced liver fibrosis. Specifically, this measure will be assessed by number of subjects experiencing treatment emergent adverse events indicative of DLT.

  Baseline; Week 1-7 (End of Study); Week 9; Week 11 (Follow-up)

Secondary Outcomes (4)

• A secondary objective is to characterize the first-dose PK profile of GR-MD-02. The PK profile is assessed by the AUC (area under the plasma concentration versus time curve) and Cmax (peak plasma concentration) of GR-MD-02.

  Baseline; Week 1-4

• A secondary objective for the study is to characterize the PK profile and serum level accumulation of GR-MD-02 following administration of 3 subsequent weekly doses given by IV infusion beginning 28 days after the first dose.

  Baseline; Week 5-7 (End of Study)

• A secondary objective is to evaluate change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), ratio of AST:ALT, alkaline phosphatase, and gamma glutamyl transpeptidase (GGTP); change in AST/platelet ratio index.

  Baseline; Week 7 (End of Study)

• A secondary objective for this study is to evaluate changes in exploratory pharmacodynamic biomarkers in serum

  Baseline; Week 7 (End of Study)

Study Arms (3)

Cohort 1

ACTIVE COMPARATOR

Patient receives dose of GR-MD-02 or placebo

Drug: GR-MD-02; Drug: Placebo

Cohort 2

ACTIVE COMPARATOR

Patient receives dose of GR-MD-02 or Placebo

Drug: GR-MD-02; Drug: Placebo

Cohort 3

ACTIVE COMPARATOR

Patient receives dose of GR-MD-02 or placebo

Drug: GR-MD-02; Drug: Placebo

Interventions

GR-MD-02 DRUG

GR-MD-02; galactoarabino-rhamnogalaturonate

Also known as: galactoarabino-rhamnogalaturonate

Cohort 1; Cohort 2; Cohort 3

Placebo DRUG

GR-MD-02 Placebo

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects meeting all of the following criteria will be considered for admission to the study:
• Institutional Review Board (IRB approved written Informed Consent and privacy language as per national regulation (eg, Health Insurance Portability and Accountability Act \[HIPAA\] Authorization for US sites) must be obtained from the subject or legally authorized representative prior to any study related procedures, including screening evaluations and tests.
• Subject is ≥ 18 years of age and \< 75 years old at the time of consent.
• Subject has had a percutaneous liver biopsy within 12 months from Screening that shows a definitive diagnosis of NASH with advanced (Brunt stage 3) hepatic fibrosis.
• Sexually active males and females of childbearing potential must agree to use adequate contraception (condoms, intra-uterine contraceptive device, implants, injectables, sexual abstinence or vasectomized partner) throughout their participation in this study and for 30 days after the last dose of study drug. Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to the first dose. Post-menopausal women must have been amenorrheic for at least 12 months to be considered of non-child-bearing potential.

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• Subject is a pregnant or lactating female.
• 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. Significant alcohol consumption is defined as more than 20 gram per day in females and more than 30 grams per day in males, on average (a standard drink in the US is considered to be 14 grams of alcohol).
• Subject is unable to reliably quantify alcohol consumption based upon local study physician judgment.
• Subject uses drugs historically associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks in the year prior to Screening.
• Subject requires use of drugs with a narrow therapeutic window metabolized by CYP3A4 such as fast acting opioids (alfentanil and fentanyl), immunosuppressive drugs (cyclosporine, sirolimus, and tacrolimus), some cardiovascular agents (ergotamine, quinidine and dihydroergotamine), and select psychotropic agents (pimozide).
• Subject has prior or has planned (during the study period) bariatric surgery (eg, gastroplasty, Roux-en-Y gastric bypass).
• Subject has concurrent infection including diagnoses of fever of unknown origin and evidence of possible central line sepsis (subjects must be afebrile at the start of therapy).
• Subject with a platelet count below 100,000/mm3 at Screening.
• Subject with clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities at Screening:
• Serum albumin less than 3.5 grams/deciliter (g/dL).
• An INR greater than 1.1.
• Direct bilirubin greater than 1.3 milligrams per deciliter (mg/dL).
• Subject has a history of bleeding esophageal varices, ascites or hepatic encephalopathy
• Subject has a history of hepatitis C. Patients found on screening to have hepatitis C antibody, even if PCR negative for HCV RNA, are excluded from this study.

Sponsors & Collaborators

• Galectin Therapeutics Inc.: lead

Study Sites (1)

Brooke Army Medical Ctr.

San Antonio, Texas, 78234, United States

Location

Related Publications (1)

• Machado MV, Diehl AM. Liver renewal: detecting misrepair and optimizing regeneration. Mayo Clin Proc. 2014 Jan;89(1):120-30. doi: 10.1016/j.mayocp.2013.10.009.

  PMID: 24388030 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

belapectin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Stephen Harrison, MD

  Brooke Army Medical Center

  PRINCIPAL INVESTIGATOR

• Naga Chalasani, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

• Ram Subramanian, MD

  Emory University Hospital (Transplant Center Clinical Research)

  PRINCIPAL INVESTIGATOR

• Thomas Schiano, MD

  The Mount Sinai Medical Center (Division of Liver Diseases)

  PRINCIPAL INVESTIGATOR

• Brent A Tetri, MD

  St. Louis University School of Medicine

  PRINCIPAL INVESTIGATOR

• Mohammad S Siddiqui, MD

  Virginia Commonwealth University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: July 9, 2013
• First Posted: July 16, 2013
• Study Start: July 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: February 23, 2015

Record last verified: 2014-06

Locations

US (1)