Rencofilstat for NASH with Advanced Liver Fibrosis

(ASCEND Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Rencofilstat for individuals with NASH, a liver condition that causes scarring and damage. The goal is to determine if Rencofilstat can improve liver health by reducing fibrosis (scarring). Participants will receive different doses of Rencofilstat or a placebo (a harmless pill with no active medicine) to compare results. Suitable candidates for this trial are adults with a confirmed diagnosis of NASH and moderate to severe liver scarring (F2 or F3 fibrosis) from a recent liver biopsy. As a Phase 2 trial, this research measures how well Rencofilstat works in an initial, smaller group, offering participants a chance to contribute to potential advancements in NASH treatment.

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.

Is there any evidence suggesting that Rencofilstat is likely to be safe for humans?

Research has shown that Rencofilstat was safe in earlier studies. Patients tolerated Rencofilstat well. In a review of 75 mg doses given to patients with NASH, no safety concerns or serious side effects emerged. This suggests that Rencofilstat could be a safe option for people with NASH and advanced liver fibrosis. However, individuals should consider their own health and consult a healthcare provider before joining any clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NASH?

Researchers are excited about Rencofilstat for treating NASH with advanced liver fibrosis because it targets the underlying mechanisms of fibrosis differently than current treatments. While most standard treatments, like lifestyle changes and medications such as vitamin E and pioglitazone, focus on managing symptoms or general liver health, Rencofilstat directly inhibits certain enzymes involved in fibrotic tissue formation. This targeted approach could potentially slow or reverse liver damage more effectively. Additionally, Rencofilstat offers various dosing options, which could provide flexibility in managing the condition based on individual patient needs.

What evidence suggests that Rencofilstat might be an effective treatment for NASH with advanced liver fibrosis?

Research has shown that Rencofilstat, a type of medication, offers potential benefits for people with NASH (a liver condition) and advanced liver scarring. In earlier studies, patients who took Rencofilstat showed noticeable improvements in liver stiffness, indicating better liver health. These results suggest that Rencofilstat might help reduce liver scarring caused by NASH. Some initial studies also found positive changes in markers related to liver health. This early evidence supports the idea that Rencofilstat could effectively treat those with NASH and liver scarring. Participants in this trial will receive different dosages of Rencofilstat or a placebo to further evaluate its effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

Stephen Harrison, MD

Principal Investigator

Pinnacle Clinical Research

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9701462/

Rencofilstat, a cyclophilin inhibitor: A phase 2a, multicenter ... The primary outcomes for the study were safety, tolerability, PK, and exploratory NASH biomarkers identified in subjects with presumed F2/F3 ...

2. journals.lww.com journals.lww.com/hepcomm/fulltext/2022/12000/rencofilstat,_a_cyclophilin_inhibitor__a_phase_2a,.9.aspx

Rencofilstat, a cyclophilin inhibitor: A phase 2a,... The primary outcomes for the study were safety, tolerability, PK, and exploratory NASH biomarkers identified in subjects with presumed F2/F3 NASH. Exploratory ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05461105

A Study to Evaluate the Safety and Efficacy of Rencofilstat ... This is a randomized, open-label, parallel-dosing, multi-center study to evaluate the safety and efficacy of rencofilstat as evidenced by assessing changes ...

4. hepionpharma.com hepionpharma.com/news/hepion-pharmaceuticals-announces-major-reductions-in-liver-stiffness-with-rencofilstat-treatment-in-17-week-phase-2-study-of-advanced-f3-mash-liver-disease/

Hepion Pharmaceuticals 17 weeks of rencofilstat treatment was associated with significant reduction in liver stiffness (FibroScan) in MASH subjects with advanced F3.

5. trialx.com trialx.com/clinical-trials/listings/220061/a-study-to-evaluate-the-efficacy-and-safety-of-rencofilstat-in-subjects-with-nash-and-advanced-liver-fibrosis/

A Study to Evaluate the Efficacy and Safety of Rencofilstat ... This is a randomized, double-blind, placebo-controlled, parallel-dosing, multi-center study to evaluate the efficacy and safety of Rencofilstat ...

6. hepionpharma.com hepionpharma.com/news/hepion-pharmaceuticals-data-safety-monitoring-board-recommends-continuation-of-phase-2a-ambition-clinical-trial-for-treatment-of-advanced-nash/

Hepion Pharmaceuticals Data Safety Monitoring Board ... Interim DSMB review at the midpoint of the first dose cohort affirmed no safety or tolerability concerns with 75 mg of Rencofilstat in NASH ...