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

Sponsor
Diffusion Pharmaceuticals Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT04573322
Collaborator
(none)
25
Enrollment
1
Location
6
Arms
7.6
Actual Duration (Months)
3.3
Patients Per Site Per Month

Study Details

Study Description

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
  • Drug: Trans Sodium Crocetinate
  • Drug: Normal saline
 Phase 1/Phase 2

Detailed Description

This trial has two phases. The first phase is an open-label, pharmacokinetic, pharmacodynamic, ascending dose, safety and tolerability lead-in. The second phase is a single-center, randomized, placebo-controlled, double-blind, adaptive, safety and efficacy, pilot.

The lead-in phase will study 4 doses of TSC and enroll 24 participants. Each TSC dose will be administered as an IV bolus injection to 6 unique participants per dose level administered four times per day (every 6 hours) for 5 days. Participants will be assigned in groups of 3, and a Safety Monitoring Committee (SMC) will review Dose Limiting Toxicities (DLTs) after each group of 3 participants. The first group of 3 participants will receive TSC at a dose of 0.25 mg/kg. If there are no DLTs, 3 additional subjects will be studied at 0.25 mg/kg. If there are 0 or 1 DLT among the 6 participants studied at 0.25mg/kg, 3 additional participants will be studied at the next higher dose, 0.5 mg/kg. If there are no DLTs an additional 3 participants will be studied at 0.5 mg/kg. If there are 0 or 1 DLTs among the 6 subjects studied at 0.5 mg/kg, 3 additional participants will be studied at the next higher dose, 1.0 mg/kg. The study will continue in this fashion seeking an observed toxicity rate that is < 0.33 among 6 participants at any one dose level, or TSC at 1.5 mg/kg proves to be safe and tolerable.

As participants complete the initial 5 days of treatment they will continue at their assigned TSC dose four times per day (every 6 hours) for up to 15 days. Participants will be assigned to dose levels in ascending order. The dose range is as follows.

  • 0.25 mg/kg TSC + Standard of Care

  • 0.50 mg/kg TSC + Standard of Care

  • 1.00 mg/kg TSC + Standard of Care

  • 1.50 mg/kg TSC + Standard of Care

At the completion of the lead-in the Safety Monitoring Committee (SMC) will examine the resultant safety and blood oxygenation (S:F) data for all participants and determine the optimum, safe and tolerable dose of TSC for use in the pilot study.

Dose Limiting Toxicity (DLT) is 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: Acute Respiratory Distress Syndrome (ARDS), Cough, Dyspnea, Hypoxia, Pneumonitis, Pulmonary Edema, Respiratory Failure, or Respiratory, Thoracic and Mediastinal disorders - Other. The SMC will apply clinical judgement in their review of adverse events (particularly abnormal laboratory results).

The two arm, randomized pilot will enroll up to 200 participants, and will be overseen by a Data Safety Monitoring Board (DSMB). TSC dosing will be at the selected optimum, safe and tolerable biologic dose with an active to placebo ratio of 2:1 toward providing the maximum potential benefit to participants. If two doses of TSC are to be studied in the randomized pilot the active to placebo ratio will be 2:2:1. Randomization will be stratified by disease severity, age and presence of pre-specified comorbidities. The treatment arms are as follows.

  • TSC + Standard of Care

  • Placebo + Standard of Care

Each TSC dose will be administered as an IV bolus injection 4 times per day (every 6 hours) for up to 15 days. Participants randomized to placebo will receive an IV bolus injection of an equivalent volume by participant weight of Normal Saline four times per day (every 6 hours) for up to 15 days.

All study drug administration will be performed by unblinded medical staff. Participants, investigators and caregivers will not see the injection or injection site or be aware of randomization.

Blood oxygenation will be measured via recorded continuous pulse oximetry and the SpO2:Fraction of Inspired Oxygen (FiO2) ratio calculated.

All participants will undergo safety and efficacy assessments including laboratory assays, blood sampling on days 1 through day 15 (while hospitalized) and day 29 by return clinic visit or if still hospitalized.

All participants, whether a part of the lead-in phase or randomized pilot, will be assessed for survival, serious adverse events and adverse events by requested return to the clinic on Day 60.

Study Design

Study Type:
Interventional
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 pilotOpen-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 :
Sep 10, 2020
Actual Primary Completion Date :
Mar 17, 2021
Actual Study Completion Date :
Apr 29, 2021

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 0.9% Sodium Chloride (NaCl)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [Up to 70 days post-study drug administration]

      Lead-in phase: Overall summary of subjects with TEAEs

    2. Time to Recovery Through Day 28 [28 days]

      Lead-in 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 0-8, as follows: 0. Uninfected - No clinical or virological evidence of infection Ambulatory - No limitation of activities Ambulatory - Limitation of activities Hospitalized, Mild Disease - Hospitalized, no oxygen therapy Hospitalized, Mild Disease - Oxygen by mask or nasal prongs Hospitalized Severe Disease - Non-invasive ventilation or high-low oxygen Hospitalized Severe Disease - Intubation and mechanical ventilation Hospitalized Severe Disease - Ventilation + additional organ support (pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO) Dead - Death

    Secondary Outcome Measures

    1. Change From Baseline in WHO Ordinal Severity Scale as a Categorical Improvement or Worsening [7 days]

      Lead-in phase: Number and percentage of patients by WHO Severity Scale change from baseline through Day 7 World Health Organization (WHO) Ordinal Severity Scale Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, no requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow O2 Hospitalized, on invasive mechanical ventilation or ECMO Death

    2. Oxygenation - Ventilator Free Days [28 days]

      Lead-in phase: Ventilator free days in the first 28 days (to day 29).

    3. Hospital Length of Stay [28 days]

      Lead-in phase: Days of treatment during the inpatient period

    4. Oxygenation - Time to Return to Baseline [28 days]

      Lead-in phase: Time to return to room air or baseline oxygen requirement

    5. Oxygenation - Pulse Oximetry [Baseline through Day 10]

      Lead-in phase: Blood oxygenation by recorded continuous pulse oximetry (SpO2:FiO2 ratio)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institute of Infectious Diseases- Prof. Dr. Matei Balş Bucharest Romania 021105

    Sponsors and Collaborators

    • Diffusion Pharmaceuticals Inc

    Investigators

    • Principal Investigator: Adrian Streinu Cercel, MD, National Institute of Infectious Diseases, Bucharest, Romania

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Diffusion Pharmaceuticals Inc
    ClinicalTrials.gov Identifier:
    NCT04573322
    Other Study ID Numbers:
    • 100-303
    First Posted:
    Oct 5, 2020
    Last Update Posted:
    Apr 14, 2022
    Last Verified:
    Apr 1, 2022
    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:
    COVID-19
    Trans-sodium crocetinate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Phase 1 lead-in was conducted; however, the study was completed prior to initiation of Phase 2. Therefore, only data are reported for the lead-in phase, as no data were collected for Phase 2.
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    Period Title: Overall Study
    STARTED 6 6 7 6
    COMPLETED 5 4 5 3
    NOT COMPLETED 1 2 2 3

    Baseline Characteristics

    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg Total
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 Total of all reporting groups
    Overall Participants 6 6 7 6 25
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    4
    66.7%
    3
    50%
    7
    100%
    5
    83.3%
    19
    76%
    >=65 years
    2
    33.3%
    3
    50%
    0
    0%
    1
    16.7%
    6
    24%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51.50
    (18.87)
    60.83
    (16.04)
    54.43
    (8.16)
    57.50
    (8.89)
    56.00
    (13.16)
    Sex: Female, Male (Count of Participants)
    Female
    3
    50%
    2
    33.3%
    4
    57.1%
    4
    66.7%
    13
    52%
    Male
    3
    50%
    4
    66.7%
    3
    42.9%
    2
    33.3%
    12
    48%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    6
    100%
    6
    100%
    7
    100%
    6
    100%
    25
    100%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    Romania
    6
    100%
    6
    100%
    7
    100%
    6
    100%
    25
    100%

    Outcome Measures

    1. Primary Outcome
    Title Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
    Description Lead-in phase: Overall summary of subjects with TEAEs
    Time Frame Up to 70 days post-study drug administration

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    Measure Participants 6 6 7 6
    Patients with any TEAE
    3
    50%
    4
    66.7%
    5
    71.4%
    2
    33.3%
    Patients with any Serious TEAE
    1
    16.7%
    1
    16.7%
    0
    0%
    0
    0%
    Patients with any TEAE of DLT
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Patients with any TEAE Resulting in Death
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    Patients with any TEAE Leading to Study Drug Discontinuation
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    Patients with any TEAE Leading to Study Drug Interruption
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Patients with any TEAE with CTCAE Grade 3 or 4
    1
    16.7%
    3
    50%
    0
    0%
    1
    16.7%
    2. Primary Outcome
    Title Time to Recovery Through Day 28
    Description Lead-in 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 0-8, as follows: 0. Uninfected - No clinical or virological evidence of infection Ambulatory - No limitation of activities Ambulatory - Limitation of activities Hospitalized, Mild Disease - Hospitalized, no oxygen therapy Hospitalized, Mild Disease - Oxygen by mask or nasal prongs Hospitalized Severe Disease - Non-invasive ventilation or high-low oxygen Hospitalized Severe Disease - Intubation and mechanical ventilation Hospitalized Severe Disease - Ventilation + additional organ support (pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO) Dead - Death
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    Measure Participants 6 6 7 6
    Mean (Standard Deviation) [days]
    14.33
    (11.54)
    13.67
    (8.43)
    7.71
    (4.31)
    7.50
    (1.22)
    3. Secondary Outcome
    Title Change From Baseline in WHO Ordinal Severity Scale as a Categorical Improvement or Worsening
    Description Lead-in phase: Number and percentage of patients by WHO Severity Scale change from baseline through Day 7 World Health Organization (WHO) Ordinal Severity Scale Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, no requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow O2 Hospitalized, on invasive mechanical ventilation or ECMO Death
    Time Frame 7 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    Measure Participants 6 6 7 6
    1 Point Worse from Day 1 to Day 7
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    No Change from Day 1 to Day 7
    3
    50%
    3
    50%
    5
    71.4%
    1
    16.7%
    1 Point Improvement from Day 1 to Day 7
    1
    16.7%
    2
    33.3%
    1
    14.3%
    5
    83.3%
    No Data Collected on Day 7
    2
    33.3%
    0
    0%
    1
    14.3%
    0
    0%
    4. Secondary Outcome
    Title Oxygenation - Ventilator Free Days
    Description Lead-in phase: Ventilator free days in the first 28 days (to day 29).
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    Measure Participants 6 6 7 6
    Mean (Standard Deviation) [days]
    19.7
    (6.05)
    16.00
    (5.33)
    15.43
    (7.28)
    19.83
    (1.17)
    5. Secondary Outcome
    Title Hospital Length of Stay
    Description Lead-in phase: Days of treatment during the inpatient period
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    Measure Participants 6 6 7 6
    Mean (Standard Deviation) [days]
    8.67
    (2.66)
    9.67
    (2.88)
    8.57
    (3.78)
    8.00
    (2.19)
    6. Secondary Outcome
    Title Oxygenation - Time to Return to Baseline
    Description Lead-in phase: Time to return to room air or baseline oxygen requirement
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    Measure Participants 6 6 7 6
    Mean (Standard Deviation) [days]
    7.50
    (5.68)
    18.92
    (18.25)
    11.79
    (7.47)
    5.50
    (2.45)
    7. Secondary Outcome
    Title Oxygenation - Pulse Oximetry
    Description Lead-in phase: Blood oxygenation by recorded continuous pulse oximetry (SpO2:FiO2 ratio)
    Time Frame Baseline through Day 10

    Outcome Measure Data

    Analysis Population Description
    There are some time points where data were not collected and, for the later timepoints, subjects discontinued.
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    Measure Participants 6 6 7 6
    Baseline (Pre First Dose)
    261.83
    (73.80)
    164.33
    (64.91)
    183.97
    (41.34)
    255.03
    (57.54)
    Day 1, Prior to Dose 1
    261.83
    (73.80)
    164.33
    (64.91)
    183.97
    (41.34)
    255.03
    (57.54)
    Day 1, 1 Minute Post Dose 1
    261.22
    (74.87)
    163.33
    (61.87)
    189.16
    (46.07)
    255.33
    (57.03)
    Day 1, 10 Minutes Post Dose 1
    261.22
    (74.90)
    164.87
    (63.89)
    188.37
    (46.00)
    255.15
    (55.76)
    Day 1, 30 Minutes Post Dose 1
    260.73
    (76.50)
    165.67
    (63.91)
    187.81
    (45.89)
    256.07
    (56.38)
    Day 1, 1.5 Hours Post Dose 1
    263.22
    (76.78)
    164.32
    (62.38)
    187.89
    (45.01)
    255.65
    (54.28)
    Day 1, 3 Hours Post Dose 1
    262.82
    (78.20)
    165.20
    (62.96)
    189.80
    (46.50)
    256.67
    (55.38)
    Day 1, Prior to Dose 2
    252.98
    (87.49)
    165.35
    (63.48)
    188.84
    (45.79)
    255.95
    (56.01)
    Day 1, Prior to Dose 3
    253.23
    (89.57)
    166.17
    (61.57)
    189.86
    (43.19)
    255.72
    (54.41)
    Day 1, Prior to Dose 4
    252.47
    (88.97)
    165.83
    (64.40)
    189.40
    (44.72)
    255.78
    (55.36)
    Day 2, Prior to Dose 1
    274.90
    (118.47)
    165.32
    (63.52)
    207.80
    (30.76)
    275.20
    (51.66)
    Day 2, 1 Minute Post Dose 1
    270.90
    (118.00)
    165.98
    (63.00)
    202.00
    (33.54)
    Day 2, Prior to Dose 2
    303.17
    (147.94)
    172.12
    (93.68)
    201.52
    (39.10)
    267.90
    (58.71)
    Day 2, Prior to Dose 3
    300.43
    (146.10)
    173.68
    (94.74)
    204.42
    (49.32)
    267.57
    (56.69)
    Day 2, Prior to Dose 4
    300.40
    (147.32)
    174.33
    (96.09)
    215.25
    (39.84)
    266.48
    (55.31)
    Day 3, Prior to Dose 1
    265.12
    (121.86)
    174.08
    (95.67)
    247.23
    (65.92)
    270.38
    (71.65)
    Day 3, 1 Minute Post Dose 1
    265.57
    (121.88)
    174.08
    (95.67)
    245.97
    (71.98)
    Day 3, Prior to Dose 2
    265.47
    (121.09)
    174.50
    (93.34)
    248.12
    (66.38)
    271.20
    (71.78)
    Day 3, Prior to Dose 3
    266.68
    (120.38)
    175.05
    (95.16)
    254.85
    (60.32)
    271.70
    (72.17)
    Day 3, Prior to Dose 4
    260.48
    (121.26)
    175.18
    (95.25)
    259.87
    (52.29)
    279.78
    (67.28)
    Day 4, Prior to Dose 1
    305.20
    (147.31)
    179.77
    (95.57)
    286.12
    (95.93)
    321.28
    (69.97)
    Day 4, Prior to Dose 2
    304.03
    (145.69)
    176.32
    (87.93)
    264.70
    (51.29)
    322.13
    (71.91)
    Day 4, Prior to Dose 3
    303.78
    (144.73)
    176.32
    (87.96)
    266.77
    (53.24)
    320.35
    (70.77)
    Day 4, Prior to Dose 4
    303.85
    (143.53)
    177.28
    (89.45)
    302.93
    (91.27)
    335.45
    (59.25)
    Day 5, Prior to Dose 1
    288.23
    (151.89)
    176.55
    (90.15)
    301.43
    (91.31)
    343.87
    (57.80)
    Day 5, Prior to Dose 2
    288.03
    (152.74)
    175.73
    (88.43)
    316.25
    (85.00)
    344.85
    (56.57)
    Day 5, Prior to Dose 3
    287.75
    (151.69)
    176.88
    (89.80)
    314.82
    (82.17)
    355.35
    (63.60)
    Day 5, Prior to Dose 4
    288.23
    (151.77)
    184.67
    (102.13)
    297.18
    (45.15)
    348.40
    (75.66)
    Day 6, Prior to Dose 1
    277.96
    (175.22)
    189.23
    (108.10)
    343.86
    (68.07)
    341.25
    (87.32)
    Day 6, Prior to Dose 2
    303.55
    (237.38)
    232.48
    (138.43)
    322.44
    (29.39)
    340.63
    (90.97)
    Day 6, Prior to Dose 3
    298.80
    (230.66)
    233.93
    (140.79)
    322.28
    (27.37)
    356.63
    (111.05)
    Day 6, Prior to Dose 4
    301.90
    (233.06)
    232.73
    (138.10)
    343.38
    (69.97)
    415.68
    (95.68)
    Day 7, Prior to Dose 1
    223.05
    (99.73)
    236.05
    (179.16)
    341.35
    (67.98)
    433.48
    (79.04)
    Day 7, Prior to Dose 2
    218.85
    (123.67)
    232.17
    (212.20)
    371.78
    (57.66)
    402.50
    (115.29)
    Day 7, Prior to Dose 3
    218.15
    (124.66)
    223.37
    (217.08)
    340.00
    (11.55)
    403.43
    (113.68)
    Day 7, Prior to Dose 4
    219.60
    (122.61)
    226.13
    (214.31)
    401.85
    (70.12)
    411.63
    (91.25)
    Day 8, Prior to Dose 1
    300.37
    (164.58)
    187.60
    (156.67)
    378.26
    (85.71)
    425.80
    (81.80)
    Day 8, Prior to Dose 2
    220.30
    (121.62)
    233.23
    (206.81)
    422.60
    (59.76)
    306.30
    Day 8, Prior to Dose 3
    216.55
    (122.40)
    248.03
    (193.52)
    385.00
    (75.75)
    306.30
    Day 8, Prior to Dose 4
    219.70
    (126.85)
    246.00
    (191.24)
    410.15
    (79.97)
    461.90
    Day 9, Prior to Dose 1
    294.75
    (229.60)
    221.45
    (166.65)
    395.48
    (79.54)
    461.90
    Day 9, Prior to Dose 2
    291.25
    (234.55)
    248.47
    (189.04)
    398.35
    (96.66)
    457.10
    Day 9, Prior to Dose 3
    293.35
    (231.58)
    149.95
    (18.88)
    395.95
    (93.27)
    457.10
    Day 9, Prior to Dose 4
    291.70
    (227.26)
    158.10
    (28.43)
    471.40
    (0.00)
    457.10
    Day 10, Prior to Dose 1
    213.80
    (130.81)
    154.67
    (23.93)
    395.03
    (82.81)
    457.10
    Day 10, Prior to Dose 2
    214.50
    (129.82)
    159.20
    (31.96)
    394.30
    (95.60)
    452.40
    Day 10, Prior to Dose 3
    122.70
    159.90
    (30.97)
    469.05
    (3.32)
    461.90
    Day 10, Prior to Dose 4
    122.70
    158.50
    (32.95)
    469.05
    (3.32)
    466.70

    Adverse Events

    Time Frame AEs were collected for up to 70 days from the start of study drug administration through the 60-day follow-up visit (+10d).
    Adverse Event Reporting Description Phase 1 lead-in was conducted; however, the study was completed prior to initiation of Phase 2. Therefore, only data are reported for the lead-in phase, as no data were collected for Phase 2.
    Arm/Group Title Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Arm/Group Description 0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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 1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days 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
    All Cause Mortality
    Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Serious Adverse Events
    Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/6 (16.7%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory Failure 1/6 (16.7%) 1 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Lead-in 0.25 mg/kg Lead-in 0.50 mg/kg Lead-in 1.0 mg/kg Lead-in 1.5 mg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/6 (50%) 4/6 (66.7%) 5/7 (71.4%) 2/6 (33.3%)
    Blood and lymphatic system disorders
    Coagulopathy 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0
    Cardiac disorders
    Bradycardia 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0
    Congestive Cardiomyopathy 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Ear and labyrinth disorders
    Excessive Cerumen Production 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0
    Gastrointestinal disorders
    Diarrhoea 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Dyspepsia 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Hernial Eventration 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Hiatus Hernia 1/6 (16.7%) 1 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Nausea 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Vomiting 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    General disorders
    Non-Cardiac Chest Pain 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0
    Oedema Peripheral 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Hepatobiliary disorders
    Hepatic Steatosis 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Hepatocellular Injury 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Infections and infestations
    Clostridium Difficile Colitis 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0
    Oral Candidiasis 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Pneumonia Bacterial 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Respiratory Tract Infection Bacterial 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Respiratory Tract Infection Fungal 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Sepsis 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Superinfection Bacterial 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Urinary Tract Infection Fungal 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 0/6 (0%) 0 2/6 (33.3%) 2 0/7 (0%) 0 0/6 (0%) 0
    Investigations
    Blood Creatinine Increased 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Electrocardiogram QT Prolonged 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Metabolism and nutrition disorders
    Hyperglycaemia 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1
    Hyperkalaemia 0/6 (0%) 0 1/6 (16.7%) 2 0/7 (0%) 0 0/6 (0%) 0
    Hypoalbuminaemia 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/6 (16.7%) 1
    Hyponatraemia 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Oedema Peripheral 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Nervous system disorders
    Paraesthesia 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0
    Psychiatric disorders
    Depression 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Insomnia 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1
    Renal and urinary disorders
    Dysuria 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 2 0/6 (0%) 0
    Urinary Retention 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 0/6 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/6 (0%) 0
    Interstitial Lung Disease 3/6 (50%) 3 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Pleural Effusion 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1
    Pulmonary Hypertension 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Respiratory Failure 1/6 (16.7%) 1 0/6 (0%) 0 0/7 (0%) 0 0/6 (0%) 0
    Vascular disorders
    Hypertension 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0
    Hypotension 0/6 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0
    Phlebitis 0/6 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Chris Galloway, MD (Chief Medical Officer)
    Organization Diffusion Pharmaceuticals
    Phone (434) 220-0718
    Email cgalloway@diffusionpharma.com
    Responsible Party:
    Diffusion Pharmaceuticals Inc
    ClinicalTrials.gov Identifier:
    NCT04573322
    Other Study ID Numbers:
    • 100-303
    First Posted:
    Oct 5, 2020
    Last Update Posted:
    Apr 14, 2022
    Last Verified:
    Apr 1, 2022