ALN-HSD for NASH with Fibrosis

(NASHGEN-2 Trial)

Recruiting at 64 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: Chronic liver disease, Substance abuse, Diabetes, Bariatric surgery, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

How does the drug ALN-HSD differ from other treatments for NASH with fibrosis?

ALN-HSD is unique because it targets specific molecular pathways involved in liver fibrosis, which is a key unmet need in treating NASH. Unlike other treatments, it may offer a novel approach by focusing on the underlying mechanisms of fibrosis progression. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new drug called ALN-HSD to help people with a liver disease called NASH. NASH causes fat to build up in the liver, leading to damage and scarring. The drug aims to reduce this damage and improve liver health.

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

This trial is for adults with a condition called NASH, where fat buildup leads to liver inflammation and scarring. Participants must have a certain level of liver damage (stage 2 or 3 fibrosis) and meet specific genetic criteria.

Inclusion Criteria

My genetic test results match the study's requirements.

Exclusion Criteria

History of Type 1 diabetes

I have a long-term liver condition.

I had or plan to have weight-loss surgery within the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the study drug ALN-HSD or placebo to assess its effect on liver scarring related to NASH

52 weeks

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ALN-HSD
• Placebo

Trial Overview The study tests ALN-HSD, an investigational drug, against a placebo to see if it can reduce liver scarring in NASH patients. It also examines how the body processes the drug and its effects on liver function and inflammation.

Participant Groups

Group I: ALN-HSD Experimental Treatment 1 Intervention

Randomized 1:1

Group II: Placebo Placebo Group 1 Intervention

Randomized 1:1

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Nonalcoholic fatty liver disease (NAFLD), now also known as metabolic dysfunction associated fatty liver disease (MAFLD), affects about 25% of the global population and can progress from benign liver fat accumulation to more severe conditions like non-alcoholic steatohepatitis (NASH).

NASH is linked to serious liver complications, including fibrosis, cirrhosis, and liver cancer, with the activation of hepatic stellate cells (HSC) playing a crucial role in the development of fibrosis, highlighting the importance of understanding the cellular interactions involved in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibrogenic Pathways in Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD). Subramanian, P., Hampe, J., Tacke, F., et al.[2022]

Leonurine hydrochloride (LH) demonstrated hepatoprotective effects in both cell and rodent models of non-alcoholic steatohepatitis (NASH), significantly improving lipid accumulation and liver enzyme levels in a dose-dependent manner over 6 weeks.

The mechanism of LH's action appears to involve the AMPK/SREBP1 pathway, as it upregulated AMPK phosphorylation and downregulated SREBP-1c and its target genes, suggesting a novel therapeutic approach for treating NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel hepatoprotective role of Leonurine hydrochloride against experimental non-alcoholic steatohepatitis mediated via AMPK/SREBP1 signaling pathway. Zhang, L., Li, HX., Pan, WS., et al.[2019]

Obeticholic acid (OCA), an FXR agonist, has shown significant improvement in hepatic fibrosis for patients with NASH stage 2/3 in a phase 3 trial, although it has side effects like itching and increased LDL cholesterol.

Several other treatments, including selonsertib and emricasan, were discontinued due to lack of efficacy, while new agents and combination therapies are being explored in ongoing phase 3 trials, indicating a continued search for effective NASH treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and new pharmacotherapy options for non-alcoholic steatohepatitis. Sumida, Y., Yoneda, M., Ogawa, Y., et al.[2022]

Nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease (NAFLD), is linked to liver damage and increased cardiovascular risk due to complex interactions between liver cells, including hepatocytes, hepatic stellate cells, and macrophages.

The activation of hepatic stem/progenitor cells (HPCs) in response to oxidative stress contributes to liver damage and fibrosis in NASH, suggesting that targeting these cellular interactions and the role of adipokines could be crucial for developing new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of hepatic progenitor cells in nonalcoholic fatty liver disease development: cellular cross-talks and molecular networks. Carpino, G., Renzi, A., Onori, P., et al.[2021]

In a study involving Wistar rats with non-alcoholic steatohepatitis (NASH), treatment with β-hydroxyphosphocarnitine (β-HPC) for 4 weeks significantly reduced liver inflammation, necrosis, and fibrosis, indicating its potential efficacy in improving liver health.

The treatment with β-HPC also led to a notable decrease in triglyceride levels and did not cause any adverse effects on liver enzyme function, suggesting it may be a safe option for managing NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats. Sánchez-Quevedo, J., Ocampo-Rodríguez, E., Alvarez-Ayala, E., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Fibrogenic Pathways in Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD). [2022]

2. France pubmed.ncbi.nlm.nih.gov

Novel hepatoprotective role of Leonurine hydrochloride against experimental non-alcoholic steatohepatitis mediated via AMPK/SREBP1 signaling pathway. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Current and new pharmacotherapy options for non-alcoholic steatohepatitis. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Role of hepatic progenitor cells in nonalcoholic fatty liver disease development: cellular cross-talks and molecular networks. [2021]

5. England pubmed.ncbi.nlm.nih.gov

β-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats. [2022]