Belapectin for NASH Cirrhosis

(NAVIGATE Trial)

Recruiting at 158 trial locations

Overseen By Julia Wattacheril, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2 & 3

Sponsor: Galectin Therapeutics Inc.

Must not be taking: Non-selective beta blockers

Disqualifiers: Alcohol abuse, Drug abuse, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

357 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing belapectin, a medication aimed at helping people with a severe liver condition called NASH cirrhosis. The study focuses on patients who have high blood pressure in their liver but no swollen veins in their esophagus. Belapectin works by reducing liver inflammation and scarring, which can improve liver function and reduce health problems.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications like vitamin E, pioglitazone, or a statin, you can continue them if the dose has been stable for at least 3 months before the trial and is expected to remain stable during the trial.

What data supports the effectiveness of the drug Belapectin for NASH cirrhosis?

Research shows that Belapectin, which blocks a protein called galectin 3, can reduce liver scarring and high blood pressure in the liver in animal studies. It was also found to be safe in early human trials. ^{1 2 3 4 5}

How is the drug Belapectin different from other treatments for NASH cirrhosis?

Belapectin is unique because it targets galectin-3, a protein involved in liver inflammation and fibrosis, which is not addressed by other treatments. This drug aims to reduce liver scarring and portal hypertension, offering a novel approach for patients with NASH cirrhosis. ^{1 4 6 7 8}

Research Team

Khurram Jamil, M.D.

Principal Investigator

Galectin Therapeutics Inc.

Eligibility Criteria

Adults aged 18-75 with NASH cirrhosis and signs of portal hypertension but no esophageal varices. They must have certain liver stiffness, blood work results, and agree to use contraception if fertile. Excluded are those with recent drug abuse, certain other liver diseases, major surgery or organ transplants within specific time frames.

Inclusion Criteria

I have abnormal blood vessels in my abdomen confirmed by a scan or physical exam.

My liver biopsy shows cirrhosis caused by fatty liver disease, with no other cause.

I have a liver condition with cirrhosis and no other liver disease causes, plus obesity, high blood pressure, diabetes, or abnormal blood fats.

Exclusion Criteria

You have liver disease that is not caused by NASH.

My kidney function is reduced, with a filtration rate under 45 mL/min.

You have taken part in a new drug research study within the past 30 days or 5 half-lives, whichever is longer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 2b

Participants receive belapectin or placebo intravenously every other week

78 weeks

Bi-weekly visits (in-person)

Treatment Phase 3

Participants continue with the optimal dose of belapectin or placebo intravenously every other week

78 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Belapectin

Trial Overview The trial is testing the effectiveness and safety of Belapectin against a placebo in preventing esophageal varices in patients with NASH cirrhosis. It's a two-stage study where participants are randomly assigned to receive either Belapectin or a placebo.

Participant Groups

Group I: belapectin 4 mg/kg lean body mass (LBM) Experimental Treatment 1 Intervention

Phase 2b: Belapectin 4 mg/kg lean body mass administered intravenously (IV) every other week for 78 weeks (18 months) Phase 3: The patient will be switched to the optimal dose

Group II: belapectin 2 mg/kg lean body mass (LBM) Experimental Treatment 1 Intervention

Phase 2b: Belapectin 2 mg/kg lean body mass administered intravenously (IV) every other week for 78 weeks (18 months) Phase 3: The patient will be switched to the optimal dose

Group III: Placebo Placebo Group 1 Intervention

Phase 2b: Placebo, administered intravenously (IV) every other week for 78 weeks (18 months) Phase 3:Placebo, administered intravenously (IV) every other week for 78 weeks (18 months)

Who Is Running the Clinical Trial?

Galectin Therapeutics Inc.

Lead Sponsor

Trials

12

Recruited

730+

Findings from Research

Non-alcoholic steatohepatitis (NASH) is a leading cause of liver failure and transplantation in the U.S., linked to conditions like obesity and type 2 diabetes, highlighting the urgent need for effective treatments.

Current first-line treatments focus on weight loss and lifestyle changes, but these may not work for patients with advanced liver disease, emphasizing the importance of ongoing drug development targeting NASH's underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs for NASH. Albhaisi, SAM., Sanyal, AJ.[2021]

In the LIVIFY trial involving 120 patients with suspected fibrotic NASH, vonafexor significantly reduced liver fat content after 12 weeks, with the 100 mg and 200 mg doses showing reductions of -6.3% and -5.4% respectively, compared to -2.3% in the placebo group.

Vonafexor was found to be safe, leading to improvements in liver enzymes, body weight, and even renal function, although mild to moderate pruritus was reported in some patients, indicating manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. Ratziu, V., Harrison, SA., Loustaud-Ratti, V., et al.[2023]

In a phase 2 trial involving 71 patients with NASH-related cirrhosis, semaglutide did not significantly improve liver fibrosis or lead to NASH resolution compared to placebo after 48 weeks.

The safety profile of semaglutide was similar to that of the placebo, with no new safety concerns identified, and common side effects included nausea and diarrhea, but overall liver and kidney function remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Loomba, R., Abdelmalek, MF., Armstrong, MJ., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

New drugs for NASH. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Pathogenesis and novel treatment options for non-alcoholic steatohepatitis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Galectin-3 inhibition as a potential therapeutic target in non-alcoholic steatohepatitis liver fibrosis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Review of galectin-3 inhibitors in the treatment of nonalcoholic steatohepatitis. [2022]