Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CS0159

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

79 Participants Needed

Trial Summary

What is the purpose of this trial?

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 absorbed, distributed, metabolized, and excreted, as well as its effects on the body.

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.

What safety data exists for the treatment known as CS0159?

The research discusses methods for evaluating drug safety, such as the benchmark dose (BMD) modeling approach, which provides more detailed information on potential toxic effects compared to traditional methods. However, it does not provide specific safety data for CS0159. ^{1 2 3 4 5}

How does the drug CS0159 differ from other treatments for this condition?

CS0159 is unique because it involves the use of synthetic oligodeoxynucleotides that activate the immune system through Toll-like receptor 9 (TLR9), which is different from many traditional treatments that may not target this specific immune pathway. This mechanism can potentially stimulate a strong immune response, making it a novel approach compared to existing therapies. ^{6 7 8 9 10}

Research Team

Kathleen Doisy, MD

Principal Investigator

Labcorp Clinical Research Unit, Inc.

Eligibility Criteria

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

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

Treatment Details

Interventions

• CS0159

Participant Groups

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

Findings from Research

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]

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]

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]

References

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

The OptiMARK clinical development program: summary of safety data. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Withdrawn 2.0-update on withdrawn drugs with pharmacovigilance data. [2023]

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

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

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

Benchmark dose-response analyses for multiple endpoints in drug safety evaluation. [2021]

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

Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies. [2016]

6. Germany pubmed.ncbi.nlm.nih.gov

Structure-activity relationship studies on the immune stimulatory effects of base-modified CpG toll-like receptor 9 agonists. [2013]

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

TLR9-independent effects of inhibitory oligonucleotides on macrophage responses to S. typhimurium. [2021]

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

CpG DNA activation and plasma-cell differentiation of CD27- naive human B cells. [2022]

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

Novel protein-based pneumococcal vaccines administered with the Th1-promoting adjuvant IC31 induce protective immunity against pneumococcal disease in neonatal mice. [2021]

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

A naturally occurring variant in human TLR9, P99L, is associated with loss of CpG oligonucleotide responsiveness. [2021]