Belapectin for NASH Cirrhosis

(NAVIGATE Trial)

Recruiting at 180 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called belapectin for individuals with nonalcoholic steatohepatitis (NASH) cirrhosis, a liver condition, who show signs of increased blood pressure in the liver but have no esophageal varices (abnormal veins in the esophagus). The goal is to determine if belapectin is safe and effective compared to a placebo (a substance with no active treatment). Participants will receive either a low or high dose of belapectin or a placebo every two weeks for about 18 months. Individuals diagnosed with NASH cirrhosis and showing signs of increased liver pressure without certain liver complications might be suitable for this trial. As a Phase 2 trial, this research measures how well belapectin works in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that belapectin, a substance that blocks the protein galectin-3, is safe for human use. In past studies, researchers administered belapectin to individuals with NASH cirrhosis and high blood pressure in the liver for one year. These studies found the treatment safe and well-tolerated, with no major safety issues reported. Additionally, earlier animal research demonstrated that belapectin reduced liver damage and high blood pressure in the liver, suggesting it could be effective without causing major side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Belapectin is unique because it targets galectin-3, a protein involved in liver inflammation and fibrosis, which is a new approach for treating NASH cirrhosis. Unlike standard treatments like lifestyle changes, vitamin E, or pioglitazone, which primarily focus on metabolic aspects and symptom management, Belapectin directly addresses the fibrotic process. Researchers are excited because this could lead to a more effective way to halt or reverse liver damage in NASH cirrhosis patients, potentially offering a breakthrough where current options fall short.

What evidence suggests that belapectin might be an effective treatment for NASH cirrhosis?

Studies have shown that belapectin, which blocks the protein galectin-3, can reduce liver scarring and high blood pressure in the veins around the liver in animal studies. In human research, belapectin was safe over a year of treatment, but it did not consistently improve conditions for all patients with NASH cirrhosis and portal hypertension. However, evidence suggests it may help prevent the development of enlarged veins in the esophagus in patients with this condition. This trial will evaluate belapectin at dosages of 2 mg/kg and 4 mg/kg lean body mass to assess its potential benefits in managing liver-related issues. ^{1 2 3 6 7}

Who Is on the Research Team?

Khurram Jamil, M.D.

Principal Investigator

Galectin Therapeutics Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31812510/

Effects of Belapectin, an Inhibitor of Galectin-3, in Patients ... Belapectin is an inhibitor of galectin 3 that reduces liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

2. investor.galectintherapeutics.com investor.galectintherapeutics.com/news-releases/news-release-details/galectin-therapeutics-announces-top-line-results-navigate

Press Release - Investor Relations | Galectin Therapeutics Inc. Galectin Therapeutics announces top-line results of NAVIGATE clinical trial evaluating Belapectin in patients with cirrhotic portal hypertension caused by MASH.

3. gastrojournal.org gastrojournal.org/article/S0016-5085(19)41895-7/fulltext

Effects of Belapectin, an Inhibitor of Galectin-3, in Patients ... In a study of patients with NASH cirrhosis, and portal hypertension, 1 year of biweekly infusion of belapectin was safe but not associated with ...

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT04365868

Belapectin for the Prevention of Esophageal Varices in NASH ... Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis · Summary · Description ...

5. navigatenash.com navigatenash.com/the-navigate-study/

The NAVIGATE Study Clinical Trial in NASH Cirrhosis An earlier clinical trial showed that belapectin, the candidate treatment, may prevent the development of esophageal varices in patients with compensated NASH ...

6. investor.galectintherapeutics.com investor.galectintherapeutics.com/news-releases/news-release-details/galectin-therapeutics-reports-positive-outcome-fifth-data-and

Press Release - Investor Relations | Galectin Therapeutics Inc. A Phase 2 study showed belapectin may prevent the development of esophageal varices in MASH cirrhosis, and these results provide the basis for ...

7. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/study-evaluating-the-efficacy-and-safety-of-belapectin-gr-md-02/

Study Evaluating the Efficacy and Safety of Belapectin (GR- ... Pre-clinical data in animal studies have shown that Belapectin has robust treatment effects reversing liver fibrosis and cirrhosis. When studied in clinical ...