Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in patients with cancer MedDRA version: 23.0 Level: LLT Classification code 10084270 Term: SARS-CoV-2 acute respiratory disease System Organ Class: 100000004862
Conditions
Interventions
Product Name: TL-895
Product Code: TL-895
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TL-895
CAS Number: 1415823-49-2
Current Sponsor code: TL-895
Other descriptive name: M7583
Concen
Sponsors
Telios Pharma, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adults =18 years of age 2. Known diagnosis of active cancer that is not considered cured or disease free. 3. Confirmed COVID-19 infection as per World Health Organization (WHO) criteria (including positive nucleic acid test of any specimen [e.g., respiratory, blood, urine, stool, or other bodily fluid] within 3 weeks of Cycle 1 Day 1) with suspected pneumonia requiring hospitalization and oxygen saturation upper limit of normal (ULN), then subjects are eligible if the direct bilirubin =2.0 × ULN b. Aspartate aminotransferase (AST) = 2.5 × ULN, and alanine aminotransferase (ALT) = 2.5 × ULN. 6. Adequate renal function defined by an estimated creatinine clearance = 30 mL/min according Cockcroft Gault 7. Ability to swallow and absorb oral medications 8. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential, must both use an effective contraception method during the study and continue to use contraception for 60 days after the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 67 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 79
Exclusion criteria
Exclusion criteria: 1. Subjects with a life expectancy of less than 6 months 2. No remaining available therapies for advanced or metastatic malignancies 3. Subjects with an advanced healthcare directive that includes a do not intubate (DNI) or do not resuscitate (DNR) orders. 5. Subjects who require chemotherapy due to active oncologic disease that cannot be suspended while receiving study treatment. 6. Subjects with new onset malignancy who require urgent systemic therapy because of active oncologic disease 7. Subjects who received systemic chemotherapy resulting in immunosuppression within 14 days of Cycle 1 Day 1. 8. Active treatment with immunomodulator medications including immune checkpoint inhibitors (PD-1, PD-L1, CTLA4 blockers) that could not be suspended for the duration of the study. 9. Subjects who received prior anti-cytokine therapy (anti-IL-6) within 5 half-lives of the drug from Cycle 1 Day 1. 10. Participation in another clinical study with therapeutic intent for COVID-19. The only exception is that patients participating in clinical trials receiving hydroxychloroquine or chloroquine and/or azithromycin and/or remdesivir will be allowed 11. Patients on warfarin at study entry 12. Patients on combined anti-platelet and therapeutic anti-coagulation therapy (LMWH or DOAC). 13. Myocardial infarct within 6 months, unstable angina, uncontrolled cardiac arrhythmia, or New York Heart Association (NYHA) class 3/4 heart failure 14. Requirement for artificial ventilation (HFNC, NiPPV, ECMO, or intubation and MV) at screening 15. Known bleeding disorders (e.g., Von Willebrand’s disease, platelet storage pool disorders, or hemophilia) 16. Stroke or intracranial hemorrhage within 6 months of Cycle 1 Day 1 17. Women who are pregnant or breastfeeding 18. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study. 19. Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV) 20. Subjects with known history of human immunodeficiency virus (HIV) 21. Grade 2 or higher QTc prolongation (> 480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [v 5.0]) 22. Disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease, etc.) 23. Patients receiving radiation therapy to the lung or mediastinum for treatment of COVID-19 24. Untreated or actively progressing known CNS lesions (carcinomatous meningitis). Patients with a history of CNS lesions are eligible, provided that all of the following criteria are met: – All known CNS lesions have been treated with radiotherapy or surgery. – Any radiotherapy or surgery must be completed = 4 weeks prior to initiation of study treatment. – No history of intracranial hemorrhage from CNS lesions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To evaluate the safety and tolerability of TL-895 in COVID-19 infected subjects and determine the recommended Phase 2 dose (RP2D) Part 2: To determine whether TL-895 plus standard available therapy (SAT) (Arm 1) can diminish the need for artificial ventilation or death as compared to placebo plus SAT (Arm 2) from Day 1 through Day 29 of study treatment;Secondary Objective: Part 1: -To determine whether TL-895 can diminish the need for artificial ventilation or death -To determine whether TL-895 decreases respiratory failure events that require invasive ventilation or death -To determine the time to hospital discharge -To examine the 1- and 3-months overall survival -To determine the proportion of subjects with viral clearance at time of hospital discharge and post discharge -To determine toxicity observed in subjects treated with TL-895 -To characterize the pharmacokinetic profile of TL-895 Part 2: -To determine whether TL-895 plus SAT (Arm 1) can diminish the need for artificial ventilation or death as compared to placebo plus SAT (Arm 2) during the study -To determine whether Arm 1 decreases respiratory failure events that require invasive ventilation or death as compared to Arm 2 during the study. -To determine the time to hospital discharge for subjects treated with Arm 1 versus Arm 2 see Protocol for full list of Secondary objectives ;Primary end point(s): Part 1: DLTs will be used to establish the RP2D. Part 2: The proportion of subjects per arm requiring artificial ventilation (intubation and mechanical ventilation [MV], extracorporeal membrane oxygenation [ECMO], heated, humidified high-flow nasal cannula oxygen [HFNC], noninvasive positive pressure ventilation [NiPPV]) or death from Day 1 through Day 29 of study treatment. ;Timepoint(s) of evaluation of this end point: Day 29 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: - The proportion of subjects requiring artificial ventilation (intubation and MV, ECMO, HFNC, NiPPV) or death - The proportion of subjects requiring intubation and MV, ECMO or death. - Duration from first dose to hospital discharge. - Time from first dose to landmark follow-up or death from any causes. - SARS-CoV-2 Nasopharyngeal Swab test by polymerase chain reaction (PCR) - Analyses of the safety endpoints will include the following measurements or assessments: physical examinations, laboratory tests, adverse events (AEs), serious AEs (SAEs), electrocardiograms (ECGs), vital signs. - TL-895 PK parameters, including but not limited to: • Predose concentration (C0h) • Concentration at 2 hours post-dose (C2h) • Maximum observed concentration (Cmax) • Time of maximum concentration (Tmax) • Area under the plasma concentration-time curve (AUC) Part2: -The proportion of subjects per arm requiring artificial ventilation (intubation and MV, ECMO, HFNC, NiPPV) or death -The proportion of subjects per arm requiring intubation and MV, ECMO or death -Duration from randomization to hospital discharge per arm. -Time from randomization to landmark follow-up or death from any causes. -SARS-CoV-2 Nasopharyngeal Swab test by polymerase chain reaction (PCR) -Analyses of the safety endpoints will include the following measurements or assessments: physical examinations, laboratory tests, adverse events (AEs), serious AEs (SAEs), electrocardiograms (ECGs), vital signs. -TL-895 PK parameters, including but not limited to: • Predose concentration (C0h) • Concentration at 2 hours post-dose (C2h) • Maximum observed concentration (Cmax) • Time of maximum concentration (Tmax) • Area under the plasma concentration-time curve (AUC);Timepoint(s) of evaluation of this end point: Days 1 and 8, Hospital Discharge, 1 and 3 months Follow-up | — |
Countries
Argentina, Brazil, France, Germany, Hungary, Italy, Peru, Philippines, Russian Federation, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactAssociate Director, Regulatory
Telios Pharma, Inc.
Outcome results
None listed