CS0159 in Healthy Volunteers

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Cascade Pharmaceuticals, Inc

Disqualifiers: Special diet, Pregnant, SARS-CoV-2, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called CS0159, an experimental treatment, in healthy volunteers. Researchers aim to assess its safety, how the body processes it, and its effectiveness. Different groups will receive varying doses either once or over 14 days to monitor for any side effects or reactions. Participants must be generally healthy with no significant medical problems. Those who meet this criteria may find this trial a suitable match. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study is for healthy volunteers, it is likely that participants should not be on any regular medications.

Is there any evidence suggesting that CS0159 is likely to be safe for humans?

Research has shown that CS0159 has undergone testing in various studies to assess its safety for humans. In one study involving patients with Non-Alcoholic Steatohepatitis (NASH), CS0159 was generally well-tolerated, with most participants experiencing no serious side effects. Another study with individuals who have Primary Biliary Cholangitis (PBC) also found the treatment to be mostly safe.

As this is an early-stage study, the primary goal is to identify any side effects and evaluate how well participants tolerate different doses. Early-stage studies like this one focus on safety, so if the study progresses, it likely indicates that the treatment has demonstrated sufficient safety for further testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CS0159 because it potentially offers a new way to manage conditions that current treatments may not fully address. Unlike other treatments, CS0159 is being explored for its unique pharmacokinetics and pharmacodynamics, which could mean improved absorption and efficacy. Additionally, the treatment's flexibility in dosing, ranging from a single low dose to daily doses over two weeks, could provide tailored options for patients, potentially improving adherence and outcomes. This fresh approach might offer new hope for patients who need alternatives to existing therapies.

What evidence suggests that this trial's treatment, CS0159, could be effective?

Research shows that CS0159 has promising results for treating certain liver conditions. In a study with patients who have Primary Biliary Cholangitis (PBC), CS0159 demonstrated strong potential for effectiveness and safety. Another study examined patients with Metabolic Associated Steatohepatitis (MASH) and found that CS0159 might work well, especially when combined with semaglutide. These findings suggest that CS0159 could help improve liver function in these conditions. Although more research is needed, early results are encouraging for its potential use in liver diseases. Participants in this trial will receive different dosages of CS0159 to further evaluate its effects. ^{1 3 4 5 6}

Who Is on the Research Team?

Kathleen Doisy, MD

Principal Investigator

Labcorp Clinical Research Unit, Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

Healthy male and non-pregnant female volunteers

In good health, determined by having no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD) Study

Participants receive a single oral dose of CS0159 or placebo in a fasted state, with a pilot food effect study for some cohorts

1 day

1 visit (in-person)

Multiple Ascending Dose (MAD) Study

Participants receive CS0159 or placebo once daily for 14 consecutive days

14 days

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CS0159

How Is the Trial Designed?

Group I: Cohort B4: 4mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 4 mg or placebo once daily for a consecutive 14 days.

Group II: Cohort B3: 2 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 2 mg or placebo once daily for a consecutive 14 days.

Group III: Cohort B2: 1 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 1 mg or placebo once daily for a consecutive 14 days.

Group IV: Cohort B1: 0.4 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 0.4 mg or placebo once daily for a consecutive 14 days.

Group V: Cohort A6: 8 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 8 mg or placebo once on Day 1.

Group VI: Cohort A5: 4 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 4 mg or placebo once on Day 1.

Group VII: Cohort A4: 2 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 2 mg or placebo once on Day 1.

Group VIII: Cohort A3: 1 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 1 mg or placebo once on Day 1 followed by a 7-day washout period then given in 1 mg tablet (in fed state) on Day 8.

Group IX: Cohort A2: 0.6 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 0.6 mg or placebo once on Day 1.

Group X: Cohort A1: 0.2 mg Experimental Treatment 1 Intervention

Participants in fasted state will receive CS0159 0.2 mg or placebo once on Day 1.

Who Is Running the Clinical Trial?

Cascade Pharmaceuticals, Inc

Lead Sponsor

Trials

9

Recruited

540+

Covance

Industry Sponsor

Trials

124

Recruited

13,300+

Dr. Paul Kirchgraber

Covance

Chief Executive Officer since 2019

MD

Dr. Robert Dow

Covance

Chief Medical Officer since 2020

MD

Published Research Related to This Trial

The benchmark dose (BMD) modeling approach provides more detailed insights into dose-response relationships in drug development compared to the traditional no-observed-adverse-effect-level (NOAEL) method, allowing for better hazard characterization.

Using BMD modeling can reduce the need for animal testing by yielding more information from fewer animals and lower doses, making it a promising alternative or complement to the NOAEL approach in assessing potential drug toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benchmark dose-response analyses for multiple endpoints in drug safety evaluation. Vieira Silva, A., Ringblom, J., Moldeus, P., et al.[2021]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

In a clinical development program involving 1684 subjects and 2038 injections, OptiMARK demonstrated a safety profile comparable to Magnevist, with 31% of its injections associated with adverse events.

OptiMARK was found to be safe and well-tolerated, showing fewer adverse events compared to Magnevist (35%) and placebo (48%), indicating its potential as a reliable imaging agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The OptiMARK clinical development program: summary of safety data. Brown, JJ., Kristy, RM., Stevens, GR., et al.[2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05896124

CS0159 in Chinese Patients With PBC (Primary Biliary ...

This is a phase II study to evaluate safety, tolerability and efficacy of CS0159 in patients with PBC (Primary Biliary Cholangitis). The study has been designed ...

2.

trial.medpath.com

trial.medpath.com/clinical-trial/115a24e103328b23

Efficacy and Safety of CS0159 Combined With Semaglutide in ...

This is an exploratory study to evaluate the efficacy, safety, and tolerability of CS0159 in combination with Semaglutide in MASH patients ...

3.

delta.larvol.com

delta.larvol.com/Products/?ProductId=98e1a12a-a858-432b-84c9-bf70fc9cf3e2

linafexor (CS0159) / Cascade Pharma

... CS0159 has demonstrated excellent efficacy and safety potential in a Phase II clinical trial for PBC. A Phase III clinical trial is planned to initiate in ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05591079

NCT05591079 | A Study to Assess the Safety, Tolerability ...

A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of CS0159 in subjects with Non-Alcoholic Steatohepatitis (NASH)

5.

withpower.com

withpower.com/trial/phase-1-cholangitis-9-2021-77a4e

Study in Healthy Volunteers to Evaluate the Safety ...

This trial tests a new drug called CS0159 in healthy people to see if it is safe and how it behaves in their bodies. Researchers will study how the drug is ...

6.

medchemexpress.com

medchemexpress.com/linafexor.html?srsltid=AfmBOooAV59LgX_2K4m085XXB4Su-k-VITlK6R3RzXX2Z2QOxzvj7m47

Linafexor (CS-0159) | FXR Agonist

SAFETY DATA SHEET (SDS). Request for HNMR Report. We have received your request and will respond to you as soon as possible. [e-mail]; 609-228 ...