HPG1860 for NASH

(RISE Trial)

Overseen By Nian Liang

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hepagene (Shanghai) Co., Ltd.

Must not be taking: Statins, PCSK9 inhibitors

Disqualifiers: Alcohol, Renal dysfunction, Cardiac issues, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HPG1860 for individuals with NASH (non-alcoholic steatohepatitis), a type of fatty liver disease. Researchers are evaluating three different doses of HPG1860 to determine their effectiveness compared to a placebo (a pill with no active medicine). The trial suits those with NASH confirmed by a biopsy or specific characteristics and a BMI over 25, but not those with serious health issues like uncontrolled diabetes or heart problems. Participants will take the treatment once daily and must adhere to the study's rules.

As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in NASH treatment.

Do I need to stop my current medications to join the trial?

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

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

Research has shown that HPG1860 is generally safe. In earlier studies, participants tolerated it well. Few side effects occurred, and these were usually mild. Common issues included headaches, drowsiness, and weakness. These side effects also appeared in those taking a placebo (a harmless pill with no active drug), suggesting they might not be directly caused by HPG1860.

In summary, current data indicates that HPG1860 seems safe. Participants experienced few problems, and the treatment appears to balance effectiveness with safety well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HPG1860 for treating non-alcoholic steatohepatitis (NASH) because it offers a novel approach compared to current options, which typically include lifestyle changes and medications like vitamin E and pioglitazone. Unlike these treatments, HPG1860 targets a different pathway in the liver that may reduce inflammation and fat buildup more effectively. This new mechanism of action could potentially lead to better outcomes for patients with NASH, providing a promising alternative to existing therapies.

What evidence suggests that this trial's treatments could be effective for NASH?

Research has shown that HPG1860 could help treat NASH, a liver condition. In earlier studies, participants tolerated HPG1860 well, and it had a strong effect on the FXR, a part of the liver crucial for health. The treatment significantly reduced a liver marker called C4, with reductions up to 97.6%. This suggests that HPG1860 might improve liver health in people with NASH. Overall, the results so far are promising and indicate that HPG1860 may be effective for this condition. Participants in this trial will receive different dosages of HPG1860 or a placebo to further evaluate its effectiveness and safety. ^{2 4 6 7 8}

Who Is on the Research Team?

Naim Alkhouri

Principal Investigator

Arizona Liver Health - Tucson

Are You a Good Fit for This Trial?

Inclusion Criteria

Body mass index (BMI) of ≥25 kg/m2 at Screening.

You are male and you agree to use a highly effective method of contraception.

You have hepatic fat assessed by a central reader.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Baseline hepatic imaging during screening

Treatment

Participants receive HPG1860 or placebo for 12 weeks

12 weeks

Regular visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HPG1860
• Placebo

How Is the Trial Designed?

Group I: HPG1860 8 mg Experimental Treatment 1 Intervention

20 subjects will be treated with HPG1860 5 mg once daily at a similar time with or without food.

Group II: HPG1860 5 mg Experimental Treatment 1 Intervention

20 subjects will be treated with HPG1860 5 mg once daily at a similar time with or without food.

Group III: HPG1860 3 mg Experimental Treatment 1 Intervention

20 subjects will be treated with HPG1860 3 mg once daily at a similar time with or without food.

Group IV: Placebo Placebo Group 1 Intervention

20 subjects will be treated with Placebo once daily at a similar time with or without food.

Who Is Running the Clinical Trial?

Hepagene (Shanghai) Co., Ltd.

Lead Sponsor

Trials

2

Recruited

150+

Published Research Related to This Trial

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

Adverse events (AEs) are reported in 49.1% of trial participants in placebo groups, indicating that these events are quite common and not solely due to the natural progression of conditions.

The prevalence of AEs in placebo groups (6.51%) is higher than in untreated groups (4.25%), suggesting that the nocebo effect may play a significant role in the experience of AEs during clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Howick, J., Webster, R., Kirby, N., et al.[2022]

SPH3127 demonstrated a dose-dependent increase in exposure and effectively suppressed plasma renin activity by up to 90% for 24 hours, indicating its potential efficacy in managing conditions related to renin activity.

The drug was well tolerated among healthy individuals, with only mild adverse events reported in 29.2% of single-dose and 33.3% of multiple-dose participants, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial. Jing, S., Xu, R., Yang, K., et al.[2021]

The Drug Adverse Reaction Database (DART) provides detailed information on 147 confirmed and 89 potential protein targets associated with adverse drug reactions (ADRs), which is crucial for understanding the mechanisms behind these reactions and aiding in drug discovery.

DART includes extensive data on 257 drugs and 1080 ligands, offering insights into their binding properties, physiological functions, and the specific adverse effects they may cause, making it a valuable resource for researchers and developers in pharmacology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Adverse Reaction Target Database (DART) : proteins related to adverse drug reactions. Ji, ZL., Han, LY., Yap, CW., et al.[2018]

Citations

1. hepagene.com hepagene.com/m_news.html

Hepagene Therapeutics Findings show that treatment with HPG1860 was safe, well-tolerated and demonstrated a robust target engagement with a favorable pharmacokinetic (PK) profile ...

2. biospace.com biospace.com/hepagene-therapeutics-reports-positive-top-line-results-for-phase-2a-rise-study-of-fxr-agonist-hpg1860-in-patients-with-nash

Hepagene Therapeutics Reports Positive Top-line Results ... In the RISE trial, once daily administration of HPG1860 for 12 weeks was generally well tolerated and most AEs were mild and moderate. Treatment ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/hepagene-phase-iia-trial-hpg1860-nash/

Hepagene begins Phase IIa clinical trial of HPG1860 to ... We have recently reported positive phase I data of HPG1860 at the 2021 AASLD meeting. ... “We look forward to assessing safety and efficacy of ...

4. prnewswire.com prnewswire.com/news-releases/hepagene-therapeutics-reports-positive-top-line-results-for-phase-2a-rise-study-of-fxr-agonist-hpg1860-in-patients-with-nash-301725438.html

Hepagene Therapeutics Reports Positive Top-line Results ... In the RISE trial, once daily administration of HPG1860 for 12 weeks was generally well tolerated and most AEs were mild and moderate. Treatment ...

5. biospace.com biospace.com/hepagene-therapeutics-inc-announces-positive-results-from-phase-i-trial-of-hpg1860

Hepagene Therapeutics, Inc. Announces Positive Results ... HPG1860 exhibited a favorable PK profile as well as robust FXR target engagement with notable C4 regression – 93.1%, 97.0% and 97.6% decrease ...

6. szabo-scandic.com szabo-scandic.com/media/product_data/msds/CAY/CAY-MSDS-CAY39481-1.pdf

Safety Data Sheet Product identifier. · Trade name: HPG1860. · Synonym. · Article number: 39481. · CAS Number: 2226133-29-3. · Application of the substance / the mixture.

7. withpower.com withpower.com/trial/phase-2-non-alcoholic-steatohepatitis-nash-10-2021-625f2

Phase 2a Study of HPG1860 in Subjects With NASH In studies involving healthy volunteers, 19% reported side effects when given a placebo, with common issues being headaches, drowsiness, and weakness. This ...

8. biospace.com biospace.com/hepagene-therapeutics-to-present-at-the-european-association-for-the-study-of-the-liver-easl-congress-2023

Hepagene Therapeutics to Present at the European ... In summary, given its significant improvement in LFC and a benign safety profile in NASH patients, HPG1860 has shown favorable risk-benefit data ...