Rencofilstat for NASH with Advanced Liver Fibrosis

(ASCEND Trial)

Recruiting at 40 trial locations

Overseen By Kristen Fetchko

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hepion Pharmaceuticals, Inc.

Must not be taking: Anticoagulants, Antidiabetics, Antifibrotics, others

Disqualifiers: Pregnancy, Hepatitis, HIV, Cardiac events, others

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

Compensation: Varies

Number of Visits: 2

Duration: 52 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests Rencofilstat, a medication that may improve liver damage, in adults with NASH and significant liver fibrosis. The drug works by reducing liver scarring and damage.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have Type 2 diabetes, you should not have recent changes in certain diabetes medications. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Rencofilstat for NASH with advanced liver fibrosis?

In a Phase 2a study, Rencofilstat showed potential benefits for patients with NASH by reducing levels of ALT (a liver enzyme), ProC3, and C6M, which are markers related to liver fibrosis. These results suggest that Rencofilstat may help reduce liver scarring, supporting its further study in larger trials. ^{1 2 3 4 5}

Is Rencofilstat safe for humans?

Rencofilstat was found to be safe and well tolerated in a Phase 2a study for patients with nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis. Common side effects included constipation, diarrhea, back pain, dizziness, and headache, but no serious safety concerns were identified. ^{1 2 4 6 7}

How does the drug Rencofilstat differ from other treatments for NASH with advanced liver fibrosis?

Rencofilstat is unique because it is a cyclophilin inhibitor that shows direct antifibrotic effects by reducing key collagen genes, which may help suppress or reverse collagen buildup in the liver. Unlike other treatments, it has demonstrated significant reductions in liver enzymes and fibrosis biomarkers, suggesting it could effectively target the underlying fibrosis in NASH. ^{1 2 8 9 10}

Research Team

Stephen Harrison, MD

Principal Investigator

Pinnacle Clinical Research

Eligibility Criteria

Adults aged 18-75 with NASH and stage 2 or 3 liver fibrosis, who have a biopsy confirming the condition within the last 6 months. Participants should not have severe heart issues, decompensated cirrhosis, recent drug trials participation, uncontrolled diabetes (HbA1c >9.5%), or infections like hepatitis B/C or HIV.

Inclusion Criteria

My liver has moderate to severe scarring according to a specific biopsy test.

Blood pressure up to 160/100 mmHg; potential subjects who meet other eligibility requirements, but who have out of range blood pressure measurements deemed to be not clinically significant by the investigator, may still be considered for study inclusion

My liver biopsy shows I have NASH with specific inflammation and cell damage.

Exclusion Criteria

Subjects with ALP >2 x ULN

Inability to undergo MRE procedure due to unremovable metal or foreign object(s) or contraindication for any other reason including but not limited to pacemaker, shrapnel injury, extensive tattoos, severe claustrophobia, ear (cochlea) implant

An estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] method)

Timeline

Screening and Randomization

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Rencofilstat or placebo for 1 year to evaluate efficacy and safety in NASH subjects with advanced liver fibrosis

52 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Rencofilstat

Trial Overview The trial is testing Rencofilstat against a placebo to see if it can improve liver fibrosis in NASH patients. It's randomized and double-blind, meaning neither doctors nor participants know who gets the real medicine versus placebo.

Participant Groups

Group I: Cohort C: Rencofilstat 225 mg Experimental Treatment 1 Intervention

Eighty-four (84) biopsy-proven NASH F2/F3 subjects to complete study on Rencofilstat 225 mg daily.

Group II: Cohort B: Rencofilstat 150 mg Experimental Treatment 1 Intervention

Eighty-four (84) biopsy-proven NASH F2/F3 subjects to complete study on Rencofilstat 150 mg daily.

Group III: Cohort A: Rencofilstat 75 mg Experimental Treatment 1 Intervention

Eighty-four (84) biopsy-proven NASH F2/F3 subjects to complete study on Rencofilstat 75 mg daily.

Group IV: Cohort D: Placebo Placebo Group 1 Intervention

Eighty-four (84) biopsy-proven NASH F2 / F3 subjects to complete study on matching placebo.

Who Is Running the Clinical Trial?

Hepion Pharmaceuticals, Inc.

Lead Sponsor

Trials

5

Recruited

330+

Findings from Research

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 52-week phase 3 trial involving 1,143 adults with presumed NASH, resmetirom was found to be safe and well tolerated, with treatment-emergent adverse events occurring in similar rates compared to placebo.

Resmetirom significantly reduced hepatic fat, LDL-C, apoB, and triglycerides, indicating its potential efficacy in treating nonalcoholic steatohepatitis and supporting further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Harrison, SA., Taub, R., Neff, GW., et al.[2023]

Lipid-lowering agents, such as statins and fibrates, have been found to be both safe and effective in treating patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), potentially reducing liver fat accumulation.

Despite concerns about liver enzyme elevation (transaminitis) in patients treated with statins, the review of studies indicates that these treatments can be beneficial, highlighting the need for larger, well-designed randomized controlled trials to confirm their efficacy and safety in various patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid-lowering agents in nonalcoholic fatty liver disease and steatohepatitis: human studies. Nseir, W., Mograbi, J., Ghali, M.[2021]

References

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

Rencofilstat, a cyclophilin inhibitor: A phase 2a, multicenter, single-blind, placebo-controlled study in F2/F3 NASH. [2023]

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

Improvements of Fibrosis and Disease Activity Are Associated With Improvement of Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis. [2023]

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

NASH Drug Development: Seeing the Light at the End of the Tunnel? [2023]

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

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

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

Current status and challenges in the drug treatment for fibrotic nonalcoholic steatohepatitis. [2023]

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

Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. [2023]

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

Lipid-lowering agents in nonalcoholic fatty liver disease and steatohepatitis: human studies. [2021]

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

What Does the Future Hold for Patients With Nonalcoholic Steatohepatitis: Diagnostic Strategies and Treatment Options in 2021 and Beyond? [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

M-PAST score is better than MAST score for the diagnosis of active fibrotic nonalcoholic steatohepatitis. [2023]

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

Hepatic Stellate Cells: Dictating Outcome in Nonalcoholic Fatty Liver Disease. [2023]