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Safety and Efficacy of Trans Sodium Crocetinate (TSC) in SARS-CoV-2 (COVID-19) Infected Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04573322
Recruitment Status : Completed
First Posted : October 5, 2020
Last Update Posted : October 29, 2021
Sponsor:
Information provided by (Responsible Party):
Diffusion Pharmaceuticals Inc

Brief Summary:
This study will assess the safety and efficacy of TSC as a treatment for participants who are infected with SARS-CoV-2 (COVID-19).

Condition or disease Intervention/treatment Phase
SARS-CoV-2 (Covid19) Drug: Trans Sodium Crocetinate Drug: Normal saline Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Open-label, pharmacokinetic, pharmacodynamic, ascending dose, safety and tolerability lead-in Single-center, randomized, placebo-controlled, double-blind, adaptive, safety and efficacy pilot
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Lead-in: no masking. Randomized pilot: The participants, care providers, investigators, and outcomes assessors are masked. The pharmacist, unblinded clinical research associate, and unblinded study drug administrator are not masked.
Primary Purpose: Treatment
Official Title: Open-label, Pharmacokinetic, Pharmacodynamic, Ascending Dose Safety lead-in Followed by a Single-center, Placebo-controlled, Double-blind, Adaptive, Safety and Efficacy, Pilot Study of Trans Sodium Crocetinate (TSC) in SARS-CoV-2 Infected Subjects
Actual Study Start Date : September 10, 2020
Actual Primary Completion Date : March 17, 2021
Actual Study Completion Date : April 29, 2021

Arm Intervention/treatment
Experimental: Lead-in 0.25 mg/kg
0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days
Drug: Trans Sodium Crocetinate
TSC, at the optimum safe and tolerable dose determined in the lead-in phase, administered via IV bolus every 6 hours for up to 15 days
Other Name: TSC

Experimental: Lead-in 0.50 mg/kg
0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days
Drug: Trans Sodium Crocetinate
TSC, at the optimum safe and tolerable dose determined in the lead-in phase, administered via IV bolus every 6 hours for up to 15 days
Other Name: TSC

Experimental: Lead-in 1.0 mg/kg
1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days
Drug: Trans Sodium Crocetinate
TSC, at the optimum safe and tolerable dose determined in the lead-in phase, administered via IV bolus every 6 hours for up to 15 days
Other Name: TSC

Experimental: Lead-in 1.5 mg/kg
1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days
Drug: Trans Sodium Crocetinate
TSC, at the optimum safe and tolerable dose determined in the lead-in phase, administered via IV bolus every 6 hours for up to 15 days
Other Name: TSC

Experimental: Randomized Active TSC
TSC, at the optimum safe and tolerable dose determined in the lead-in phase, administered via IV bolus every 6 hours for up to 15 days
Drug: Trans Sodium Crocetinate
TSC, at the optimum safe and tolerable dose determined in the lead-in phase, administered via IV bolus every 6 hours for up to 15 days
Other Name: TSC

Placebo Comparator: Randomized Placebo
Normal Saline, in an equivalent volume by participant body weight, administered via IV bolus every 6 hours for up to 15 days
Drug: Normal saline
Normal Saline, in an equivalent volume by participant body weight, administered via IV bolus every 6 hours for up to 15 days
Other Name: 0.9% Sodium Chloride (NaCl)




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 5 days ]
    Lead-in phase: Serious adverse events and DLTs, defined as any study drug related grade 3 or 4 adverse event during the treatment period, with the exception of pulmonary events in the CTCAE that are known complications of SARS-CoV-2 infection: ARDS, Cough, Dyspnea, Hypoxia, Pneumonitis, Pulmonary Edema, Respiratory Failure, or Respiratory, Thoracic and Mediastinal disorders - Other.

  2. Time to recovery through Day 28 [ Time Frame: 28 days ]

    Randomized phase: Time to achieve (and maintain through Day 28) a World Health Organization (WHO) ordinal COVID-19 severity scale score of 1, 2 or 3 with a minimum 1-point improvement from baseline. The scale assesses clinical status and the range is 0-9, as follows:

    0. Uninfected - No clinical or virological evidence of infection

    1. Ambulatory - No limitation of activities
    2. Ambulatory - Limitation of activities
    3. Hospitalized, Mild Disease - Hospitalized, no oxygen therapy
    4. Hospitalized, Mild Disease - Oxygen by mask or nasal prongs
    5. Hospitalized Severe Disease - Non-invasive ventilation or high-low oxygen
    6. Hospitalized Severe Disease - Intubation and mechanical ventilation
    7. Hospitalized Severe Disease - Ventilation + additional organ support (pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO)
    8. Dead - Death


Secondary Outcome Measures :
  1. WHO Ordinal Severity Scale [ Time Frame: 28 days ]
    Proportion of subjects with WHO ordinal severity scale score of 6 or 7 at any time through Day 28

  2. WHO Ordinal Severity Scale - Time to Improvement [ Time Frame: 28 days ]
    Time to an improvement of one category (i.e., a 1-point improvement) from baseline

  3. WHO Ordinal Severity Scale - Change from Baseline [ Time Frame: 28 days ]
    • Change from baseline in WHO scale score at days 2, 4, 7, 10, 14 and 28, as a categorical improvement or worsening
    • Mean change in WHO ordinal severity scale score from baseline through days 2, 4, 7, 10, 14 and 28

  4. National Early Warning Score (NEWS) [ Time Frame: 28 days ]

    • The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first

    The NEWS score determines the degree of illness of a patient and prompts critical care intervention. The following physiological parameters are assessed on a scale of 0 to 3, with a higher score indicating a more critical condition:

    1. Respiration rate
    2. Oxygen saturation (SpO2)
    3. Air or oxygen
    4. Systolic blood pressure
    5. Pulse rate
    6. Level of consciousness or new confusion
    7. Temperature

  5. National Early Warning Score (NEWS) - Change from Baseline [ Time Frame: 28 days ]
    Change from baseline through days 2, 4, 7, 10, 14 and 28 in NEWS

  6. Mechanical Ventilation [ Time Frame: 28 days ]
    Ventilator free days in the first 28 days (to day 29).

  7. Mechanical Ventilation - Duration [ Time Frame: 28 days ]
    Incidence and duration of new mechanical ventilation use during the trial

  8. Hospitalization [ Time Frame: 28 days ]
    • Hospital length of stay by Day 29
    • ICU length of stay by Day 29

  9. Oxygenation [ Time Frame: 28 days ]
    • Oxygenation free days in the first 28 days from start of therapy
    • Days on extracorporeal membrane oxygenation (ECMO)

  10. Oxygenation - New Oxygen Use [ Time Frame: 28 days ]
    Incidence and duration of new oxygen use during the trial

  11. Oxygenation - Advanced Therapies [ Time Frame: 28 days ]
    Proportion on mechanical ventilation, ECMO, noninvasive ventilation and high-flow nasal cannula oxygen delivery and return to room air or baseline oxygen requirement

  12. Oxygenation - Time to Return to Baseline [ Time Frame: 28 days ]
    Time to return to room air or baseline oxygen requirement

  13. Oxygenation - Pulse Oximetry [ Time Frame: 28 days ]
    Blood oxygenation by recorded continuous pulse oximetry (SpO2:FiO2 ratio)

  14. Oxygenation - ABG Measurements [ Time Frame: 28 days ]
    Blood oxygenation by serial arterial blood gas measurements collected prior to the first dose of TSC and at 1 minute, 10 minutes, 30 minutes, 1.5 hours, 3 hours and 6 hours post TSC administration by calculated PaO2:FiO2 ratios

  15. Mortality [ Time Frame: Up to 60 days ]
    • 15-day mortality
    • 28-day mortality
    • All-cause mortality at day 29
    • In hospital mortality
    • Mortality at Day 60



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Hospitalized subjects with confirmed SARS-CoV-2 infection and hypoxemia, defined as SpO2 < 94% on room air or requiring supplemental oxygen
  2. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 72 hours prior to enrollment.
  3. WHO ordinal scale score of 3, 4 or 5 at baseline
  4. Male or non-pregnant female adult ≥18 years of age at time of enrolment.
  5. Subject (or legally authorized representative (LAR)) provides written informed consent prior to initiation of any study procedures.
  6. Understands and agrees to comply with planned study procedures.
  7. Illness of any duration
  8. Women of childbearing potential must have a negative blood pregnancy test at the screening/baseline visit (Day 1) and agree to use a double method of birth control through 30 days after the last dose of study drug.

Exclusion Criteria:

  1. Intubated and mechanically ventilated at baseline
  2. Receiving extracorporeal membrane oxygenation (ECMO) at baseline
  3. Severe organ dysfunction (SOFA score > 10)
  4. Patient or LAR unable to provide written informed consent
  5. ALT/AST > 3 times the upper limit of normal or serum bilirubin > 1.5 times the upper limit of normal
  6. Estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD) formula < 30 mL/min/1.73 m^2 or on dialysis
  7. Pregnancy or breast feeding.
  8. Anticipated transfer to another hospital which is not a study site within 72 hours.
  9. Allergy to any study medication

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04573322


Locations
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Romania
National Institute of Infectious Diseases- Prof. Dr. Matei Balş
Bucharest, Romania, 021105
Sponsors and Collaborators
Diffusion Pharmaceuticals Inc
Investigators
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Principal Investigator: Adrian Streinu Cercel, MD National Institute of Infectious Diseases, Bucharest, Romania
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Responsible Party: Diffusion Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT04573322    
Other Study ID Numbers: 100-303
First Posted: October 5, 2020    Key Record Dates
Last Update Posted: October 29, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Diffusion Pharmaceuticals Inc:
Hypoxemia
Hypoxia
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Trans-sodium crocetinate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Anticarcinogenic Agents
Antineoplastic Agents