Non-Alcoholic Steatohepatitis (NASH)Phase 1NCT01899859

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

A Phase 1 study testing GR-MD-02 in people with Non-Alcoholic Steatohepatitis (NASH), run by Galectin Therapeutics Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 74 years
Conditions the study is for: Non-Alcoholic Steatohepatitis (NASH)
What is being tested?: GR-MD-02
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 1 siteUnited States
Study dates: Jul 2013to Feb 2015
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 74 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

Show all 43Show fewer

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.
Subject has evidence of other forms of chronic liver disease:
Hepatitis B as defined by presence of hepatitis B surface antigen.
Evidence of ongoing autoimmune liver disease as defined by compatible liver histology.
Primary biliary cirrhosis as defined by the presence of at least 2 of these criteria (i) Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation (ii) Presence of anti-mitochondrial antibody (iii) Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts.
Primary sclerosing cholangitis.
Wilson's disease as defined by ceruloplasmin below the limits of normal and compatible liver histology.
Alpha-1-antitrypsin deficiency as defined by diagnostic features in liver histology (confirmed by alpha-1 antitrypsin level less than normal; exclusion at the discretion of the study physician).
History of hemochromatosis or iron overload as defined by presence of 3+ or 4+ stainable iron on liver biopsy.
Drug-induced liver disease as defined on the basis of typical exposure and history.
Known bile duct obstruction.
Suspected or proven liver cancer.
Any other type of liver disease other than NASH.
Subject with serum ALT greater than 300 units per liter (U/L) at Screening.
Subject with serum creatinine of 1.5 mg/dL or greater at Screening.
Subject using of any prescription or over-the-counter medication or herbal remedy that are believed to improve or treat NASH or liver disease or obesity during the period beginning 30 days prior to randomization. Subjects who are using Vitamin E or omega-3 fatty acids may continue their use.
Subject had major surgery within 8 weeks prior to Day 0, significant traumatic injury, or anticipation of need for major surgical procedure during the course of the study.
Subject with a history of biliary diversion.
Subject with known positivity for Human Immunodeficiency Virus infection.
Subject with an active, serious medical disease with likely life expectancy of less than 5 years.
Subject with active substance abuse, including inhaled or injection drugs, in the year prior to Screening.
Subject who has clinically significant and uncontrolled cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or Grade II or greater peripheral vascular disease within 12 months prior to Day 0.
Subject has participated in an investigational new drug (IND) trial in the 30 days before randomization.
Subject has a clinically significant medical or psychiatric condition considered a high risk for participation in an investigational study.
Subject has any other condition which, in the opinion of the Investigator, would impede compliance or hinder completion of the study.
Subject has been previously exposed to GR MD 02.
Subject with known allergies to the study drug or any of its excipients.
Subject with malignant disease (other than basal and squamous cell carcinoma of the skin and in situ carcinoma of the cervix) with at least 5 years of follow-up showing no recurrence.
Subject has an abnormal chest x-ray indicative of acute or chronic lung disease on screening examination.

Trial locations and contacts

1 site in 1 country.

United States1 site

Brooke Army Medical Ctr.
San Antonio, Texas, 78234

Other trials in United States

About this study

Official title: A Multi-Center, Partially Blinded, Maximum Tolerated Multiple Dose Escalation, Phase 1 Clinical Trial to Evaluate the Safety of GR-MD-02 in Subjects With Non-Alcoholic Steatohepatitis (NASH)With Advanced Hepatic Fibrosis

Read the detailed description

This study is a dose ranging study to assess in sequential fashion, the safety, tolerability, and dose limiting toxicities (DLTs) of GR-MD-02, in subjects with biopsy-proven NASH with advanced fibrosis. This is a dose escalation design comprised of 3 sequential cohorts to evaluate the safety of GR MD 02 when administered as a single IV infusion followed by 3 additional weekly infusions starting 28 days after the first dose. Each cohort will consist of 8 subjects, 6 randomized to receive active drug and 2 randomized to receive placebo.Based on data safety monitoring board (DSMB) and FDA review, 2 additional cohorts may be implemented, consisting of 8 subjects.

Conditions: Non-Alcoholic Steatohepatitis (NASH)
Being tested: GR-MD-02, Placebo
Keywords: Non-Alcoholic Steatohepatitis (NASH)
Medical subject headings: Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GR-MD-02Drug
Also called galactoarabino-rhamnogalaturonate
GR-MD-02; galactoarabino-rhamnogalaturonate
PlaceboDrug
GR-MD-02 Placebo

Study groups in NCT01899859
Study group	Role	What they receive
Cohort 1	Active comparator	Patient receives dose of GR-MD-02 or placebo Receives: Drug: GR-MD-02; Drug: Placebo
Cohort 2	Active comparator	Patient receives dose of GR-MD-02 or Placebo Receives: Drug: GR-MD-02; Drug: Placebo
Cohort 3	Active comparator	Patient receives dose of GR-MD-02 or placebo Receives: Drug: GR-MD-02; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
A secondary objective for the study is to characterize the first-dose PK profile of GR-MD-02 administered as an IV infusion. Specifically, 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.
Measured: 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.
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.
Measured: 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.
A secondary objective for this study is to evaluate change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), ratio of AST:ALT, alkaline phosphatase, and gamma glutamyl transpeptidase (GGTP) levels; and change in AST/platelet ratio index.
Measured: Baseline; Week 7 (End of Study)
A secondary objective for this study is to evaluate changes in exploratory pharmacodynamic biomarkers in serum
A secondary objective for this study is to evaluate levels of exploratory pharmacodynamic biomarkers in serum including galectin-3, inflammatory, cell-death, and fibrosis markers.
Measured: Baseline; Week 7 (End of Study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2013Feb 2015

First posted16 Jul 2013 (estimated)
Study startJul 2013
Primary completionFeb 2015
Study completionFeb 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Non-Alcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01899859
Sponsor's protocol ID: GT-020
Status last verified: Jun 2014
First submitted: 9 Jul 2013
Last updated: 23 Feb 2015
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 24388030

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Non-Alcoholic Steatohepatitis (NASH) trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-Center, Partially Blinded, Maximum Tolerated Multiple Dose Escalation, Phase 1 Clinical Trial to Evaluate the Safety of GR-MD-02 in Subjects With Non-Alcoholic Steatohepatitis (NASH)With Advanced Hepatic Fibrosis
ClinicalTrials.gov ID: NCT01899859
Acronym / sponsor ID: GT-020
Conditions: Non-Alcoholic Steatohepatitis (NASH)
Keywords: Non-Alcoholic Steatohepatitis (NASH)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Galectin Therapeutics Inc.Industry (pharma, biotech, devices)
Study start: Jul 2013
Primary completion: Feb 2015 (actual)
Study completion: Feb 2015 (actual)
First posted: 16 Jul 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Cohort 1	Active comparator	Drug: GR-MD-02, Drug: PlaceboPatient receives dose of GR-MD-02 or placebo
Cohort 2	Active comparator	Drug: GR-MD-02, Drug: PlaceboPatient receives dose of GR-MD-02 or Placebo
Cohort 3	Active comparator	Drug: GR-MD-02, Drug: PlaceboPatient receives dose of GR-MD-02 or placebo

Who may qualify

Ages: 18 to 74 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (43 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GR-MD-02Also: galactoarabino-rhamnogalaturonateGR-MD-02; galactoarabino-rhamnogalaturonate	Drug	Cohort 1, Cohort 2, Cohort 3
PlaceboGR-MD-02 Placebo	Drug	Cohort 1, Cohort 2, Cohort 3

Primary outcome

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.
Time frame: Baseline; Week 1-7 (End of Study); Week 9; Week 11 (Follow-up)
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.

4 secondary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline; Week 7 (End of Study)
A secondary objective for this study is to evaluate changes in exploratory pharmacodynamic biomarkers in serum
Time frame: Baseline; Week 7 (End of Study)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2015.
Derived from this study: PubMed 24388030Machado 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.

Related trials for Non-Alcoholic Steatohepatitis (NASH)

Not yet recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stephen Harrison, MD principal investigator

Brooke Army Medical Center

Naga Chalasani, MD principal investigator

Indiana University

Ram Subramanian, MD principal investigator

Emory University Hospital (Transplant Center Clinical Research)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GR-MD-02 in people with Non-Alcoholic Steatohepatitis (NASH), run by Galectin Therapeutics Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Baseline; Week 1-7 (End of Study); Week 9; Week 11 (Follow-up)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01899859, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2015.