What Is CX-4945?
CX-4945, also known by its investigational name Silmitasertib, is a drug currently under study. It is being investigated for its potential to treat various medical conditions. The provided trial descriptions indicate that CX-4945 is administered as an API powder-in-capsule, typically in a 200 mg strength. While the specific mechanism of action is not detailed in the available trial information, it is being explored as a treatment across a range of diseases.
Currently, CX-4945 is being investigated in 6 clinical trials for several conditions, including various cancers and infectious diseases. A total of 304 participants have been enrolled to evaluate its safety and effectiveness. The first trial for CX-4945 began in 2009, with the latest trial starting in 2024. These studies aim to understand how the drug works and its potential benefits for patients.
Uses and Conditions Under Study
CX-4945 is being investigated in clinical trials for a variety of serious conditions, primarily focusing on different types of cancer and infectious diseases. A total of 6 trials have been conducted or are ongoing, enrolling 304 participants.
- Cancers: CX-4945 is being studied as a potential treatment for several forms of cancer, including Multiple Myeloma (in 2 trials), Breast Cancer, Inflammatory Breast Cancer, Carcinoma, Basal Cell, Cholangiocarcinoma, and Advanced Solid Tumors.
- Infectious and Inflammatory Diseases: The drug is also being evaluated for its role in treating certain infections and inflammatory conditions, such as COVID-19, Influenza With Pneumonia, Community-acquired Pneumonia, and Castleman's Disease.
These studies aim to determine the safety and effectiveness of CX-4945 across these diverse medical challenges.
Dosing
CX-4945 is formulated as capsules, containing the active pharmaceutical ingredient (API) as a powder. The primary strength studied is 200 mg per capsule, though trials have explored various dosing regimens and strengths.
Dosing schedules for CX-4945 have varied significantly depending on the condition being studied and the phase of the clinical trial:
- For conditions such as SARS-CoV-2 (COVID-19) and influenza, CX-4945 has been administered at a dose of 400 mg twice daily (BID) for up to 5 days, often in addition to standard of care (SOC).
- In some cancer studies, CX-4945 capsules have been given as escalating doses, either twice daily or four times daily, for 21 consecutive days followed by a 7-day break, completing a 28-day cycle.
- Other strengths studied include 200 mg once daily (QD) and 200 mg BID.
These diverse dosing strategies are part of the ongoing research to identify the most effective and safest way to administer CX-4945 for each specific indication.
Side Effects
The most common side effect reported in a clinical trial involving CX-4945 was diarrhea. 50.0% of patients taking CX-4945 experienced diarrhea, compared to 18.2% of patients on placebo. This data comes from a single clinical trial with 22 participants receiving CX-4945.
Other common side effects included:
- Nausea: 22.7% of patients on CX-4945 experienced nausea, compared to 4.5% on placebo.
- Dysphonia (difficulty speaking): 9.1% of patients on CX-4945 experienced dysphonia, compared to 0.0% on placebo.
- Dizziness: 9.1% of patients on CX-4945 experienced dizziness, compared to 0.0% on placebo.
- Cough: 4.5% of patients on CX-4945 experienced cough, compared to 0.0% on placebo.
- Conjunctival hyperaemia (eye redness): 4.5% of patients on CX-4945 experienced conjunctival hyperaemia, compared to 0.0% on placebo.
- Contusion (bruising): 4.5% of patients on CX-4945 experienced contusion, compared to 0.0% on placebo.
- Dysgeusia (altered taste): 4.5% of patients on CX-4945 experienced dysgeusia, compared to 0.0% on placebo.
Clinical Trial Results
Basal Cell Carcinoma (BCC)
A study (NCT03897036) investigated the appropriate dose for CX-4945 in patients with Basal Cell Carcinoma. The recommended Phase 2 dose determined in this study was 1000 mg.
Healthy Subjects
In a study involving healthy subjects (NCT05817708), various doses of CX-4945 were evaluated for their effects on blood chemistry and safety. Changes in blood chemistry markers were observed across different dosing regimens. For example, some markers showed mean reductions ranging from -0.3 U/L to -65.1 U/L, while others showed small increases, such as 0.1 U/L to 3.4 U/L. The specific markers and their clinical significance were not detailed in the provided data. The study also monitored for heart rhythm abnormalities; between 3 and 9 participants across the different CX-4945 dosing groups (200mg once daily, 200mg twice daily, and 400mg twice daily) were evaluated as having abnormalities in their ECGs. Additionally, 1 to 7 participants experienced treatment-emergent adverse events, depending on the dose received. The total number of participants in each dosing group was not provided for percentage calculations.
Viral Community Acquired Pneumonia (CAP)
A study (NCT06202521) evaluated CX-4945 in combination with standard of care (SOC) for patients with CAP caused by influenza virus or SARS-CoV-2. The results were compared to placebo plus SOC. The total number of participants in each group was not provided for percentage calculations, so results are presented as counts or mean changes.
- Oxygenation (SpO2/FiO2 Ratio): For patients with influenza virus CAP, those receiving CX-4945 + SOC showed a mean increase in their SpO2/FiO2 ratio of approximately 3.32, compared to a mean increase of approximately 1.55 for those on placebo + SOC. For SARS-CoV-2 CAP, the mean increases were similar: approximately 1.16 for CX-4945 + SOC and 1.23 for placebo + SOC. A higher ratio indicates better oxygenation.
- Health Improvement: In the influenza domain, 2 participants receiving CX-4945 + SOC showed health improvement on the NIAID 8-point Ordinal Scale, compared to 1 participant on placebo + SOC. In the SARS-CoV-2 domain, 2 to 5 participants on CX-4945 + SOC showed health improvement, compared to 1 to 2 participants on placebo + SOC.
- Pulmonary X-ray Findings: For influenza CAP, 19 participants on CX-4945 + SOC showed improved pulmonary X-ray findings, compared to 18 participants on placebo + SOC. For SARS-CoV-2 CAP, 45 participants on CX-4945 + SOC showed improved pulmonary X-ray findings, compared to 43 participants on placebo + SOC.
- Fever Resolution: The median time to fever resolution for influenza CAP was 1.8 days for CX-4945 + SOC and 1.7 days for placebo + SOC. For SARS-CoV-2 CAP, the median time was 1.8 days for CX-4945 + SOC and 1.2 days for placebo + SOC.
No participants in either the CX-4945 + SOC or placebo + SOC groups for either influenza or SARS-CoV-2 CAP required hospitalization, emergency room visits, or died due to the progression of CAP. One participant in the CX-4945 + SOC influenza group experienced all-cause hospitalization, emergency room visit, or death during the study period, and one participant in the placebo + SOC SARS-CoV-2 group experienced the same.
Currently Recruiting Trials
Currently, there are no clinical trials for CX-4945 actively recruiting new participants. This means that no studies are presently seeking volunteers to test this investigational drug. Patients interested in CX-4945 should consult with their healthcare provider and monitor official clinical trial registries for any future studies that may open.
Where to Participate
At this time, no clinical trial sites for CX-4945 are open and accepting participants. This means there are no locations in any city or state where you can enroll in a study for this drug right now. When trials for CX-4945 have been conducted, eligibility criteria have typically included participants of all genders. However, these studies have not included healthy volunteers or children. Specific age ranges would be detailed for each individual study. Interested individuals should consult with their doctor for personalized advice.
Development Timeline
The journey of CX-4945 in clinical development began on May 1, 2009. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia. Early development was supported by Cylene Pharmaceuticals, which sponsored two trials. As research progressed, Senhwa Biosciences, Inc. took on a leading role, sponsoring four trials and significantly broadening the scope of investigation for CX-4945.
Across its development, CX-4945 has been studied in a total of six clinical trials, involving 304 participants. The majority of these studies have focused on early-stage research, with four trials conducted in Phase 1 and one in Phase 1/Phase 2. One study has reached Phase 2, indicating progression in understanding its effects.
Over time, the potential applications for CX-4945 have expanded considerably beyond its initial indications. The drug has been investigated for a diverse range of conditions, including:
- Carcinoma, Basal Cell
- Castleman's Disease
- Cholangiocarcinoma
- Community-acquired Pneumonia
- COVID-19
- Inflammatory Breast Cancer
- Influenza With Pneumonia
- Advanced Solid Tumors
- SARS-CoV-2 -Associated Pneumonia
The most recent trial for CX-4945 began on January 11, 2024, continuing its ongoing exploration in various therapeutic areas.