Silmitasertib (CX-4945) in Patients With Severe Coronavirus Disease 2019 (COVID-19)

NCT04668209 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CX4945-AV02-IIT
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

This multi-center, open-label, 2 arm parallel-group, randomized, interventional prospective exploratory study in 40 patients aimed to evaluate safety and explore putative clinical benefits of Silmitasertib 1000 mg BID dose in patients with severe illness caused be SARS-COV-2. This will be a two-arm trial comparing the SOC/best supportive care alone to the SOC/best supportive care with addition of Silmitasertib (allocation ratio 1:1).

Conditions

Coronavirus

Keywords

SARS-CoV-2; COVID-19

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]

  Adverse Events experienced by the patients from randomization to Day 60 (including vital signs, physical findings, clinical laboratory, and ECG results) as characterized by type, frequency, severity (as graded by Common Terminology Criteria for Adverse Events (CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

  Through Day 60

Secondary Outcomes (22)

• To Compare Time to Clinical Recovery in CX-4945 Treatment Group Evaluated From Randomization Through Day 28 as Compared to the Control Arm.

  Through Day 28

• To Compare Time to Clinical Recovery in CX-4945 Treatment Group Evaluated From Randomization Through Day 28 as Compared to the Control Arm.

  Through hospital discharge, an average of 28 days

• To Compare Time to Clinical Recovery in CX-4945 Treatment Group Evaluated From Randomization Through Day 28 as Compared to the Control Arm.

  Through Day 28

• To Compare Changes in Clinical Status of Patients Enrolled to CX-4945 Treatment Arm as Compared to the Control Arm at Day 14 and Day 28.

  Assessed on Day 14 and Day 28

• To Compare Changes in Clinical Status of Patients Enrolled to CX-4945 Treatment Arm as Compared to the Control Arm at Day 14 and Day 28.

  Through Day 28

Study Arms (2)

Silmitasertib

ACTIVE COMPARATOR

Standard of care / supportive care in combination with Silmitasertib (CX-4945)

Drug: Silmitasertib

Standard of Care

NO INTERVENTION

Standard of care / supportive care

Interventions

Silmitasertib DRUG

Standard of care / best supportive care in combination with CX-4945 1000 mg administered orally, two times a day.

Also known as: CX-4945

Silmitasertib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-pregnant female adult ≥ 18 years of age
• Diagnosed/confirmed with COVID-19 by standard RT-PCR assay or equivalent testing within 7 days prior to randomization (Day1).
• Hospitalized patient with severe illness caused by SARS-CoV-2 (Note: Prior or current use of remdesivir or dexamethasone (SOC) are allowed under the investigator's discretion. Concomitant treatment with other investigational antiviral drugs or immunomodulators are not permitted from Day1 through Day 28)
• Symptoms of severe systemic illness/infection with COVID-19:
• At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory infection including dyspnea at rest or respiratory distress AND Clinical signs indicative of severe systemic illness/infection with COVID-19 At least 1 of the following: RR ≥ 30, HR ≥ 125, SaO2 \<93% on room air or requires \> 2L oxygen by nasal cannula in order to maintain SaO2 ≥93%
• Patient (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
• Adequate hematopoietic capacity, as defined by the following:
• Hemoglobin ≥ 9.0 g/dL and not transfusion dependent
• Platelets ≥ 100,000/mm3
• Absolute neutrophil count ≥ 1500 cells/mm3
• Adequate hepatic function, as defined by the following:
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• Albumin ≥ 3.0 g/dL
• Adequate renal function, as defined by the following:

You may not qualify if:

• Patient showing signs of respiratory failure necessitating mechanical ventilation
• Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a man father a child, or a woman become pregnant or suspect she is pregnant while participating in this study, he or she should inform the treating physician immediately.
• Active or uncontrolled infections other than COVID-19 or with serious illnesses or medical conditions which would not permit the patient to receive study treatment
• Active or planned concomitant treatment with other investigational antivirals or immunomodulators
• Chronic diarrhea (excess of 2-3 stools/day above normal frequency)
• Current use or anticipated need for drugs that are known strong inhibitors or inducers of major CYP enzymes.

Sponsors & Collaborators

• University of Arizona: lead
• Senhwa Biosciences, Inc.: collaborator

Study Sites (2)

Banner University Medical Center Phoenix

Phoenix, Arizona, 85006, United States

Location

Banner University Medical Center Tucson

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

silmitasertib

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

After 15 months of active enrollment and a lack of qualifying hospitalized COVID-19 patients, the Sponsor-Investigator, Marilyn Csete Glassberg, MD, decided to terminate recruitment before meeting the stated enrollment objectives.

Results Point of Contact

• Title: Jessica Winters
• Organization: University of Arizona

jwinters1@arizona.edu

520-780-1882

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 16, 2020
• Study Start: January 21, 2021
• Primary Completion: June 30, 2022
• Study Completion: October 19, 2022
• Last Updated: November 7, 2023
• Results First Posted: August 14, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)