Pneumonia
Conditions
Keywords
COVID-19, Coronavirus, Pneumonia, Calcium Release-Activated Calcium Channel (CRAC) Inhibitors, CM4620, Auxora
Brief summary
This is a single-blind study of Auxora in patients with critical COVID-19 pneumonia, consisting of up to 3 cohorts of escalating dose. The main goal was to assess pharmacodynamic parameters of immune response, while also assessing safety and tolerability of the drug in this patient population.
Detailed description
The primary objective of this study was to assess the pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets and chemokine release to various doses of Auxora in patients with critical COVID-19 pneumonia. Other objectives included assessment of safety and tolerability of Auxora in patients with critical COVID-19 pneumonia, as well as pharmacokinetic profile of Auxora in these patients. Efficacy was also to be examined based on all-cause mortality at day 60, number of days on mechanical ventilation after randomization, number of days in the hospital after randomization, and number of days in the ICU after randomization. Patients were randomized 3:1 to Auxora or Placebo. The first 4 patients were enrolled in Cohort 1 (3 Auxora, 1 Placebo). If dose escalation occurred, the next 4 patients were to be enrolled in Cohort 2. If dose escalation occurred again, the next 8 patients were to be enrolled in Cohort 3. The decision to escalate dosing was made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2. (Note: Trial terminated early after the first patient was enrolled in Cohort 3 due to lack of new Covid-19 hospitalizations.)
Interventions
DRUGCM4620-IE (Injectable Emulsion)
Auxora is an injectable emulsion containing 1.6mg/ML of the active pharmaceutical ingredient CM4620. Auxora will be administered intravenously as a continuous infusion
DRUGPlacebo
Matching placebo is an injectable emulsion containing no active pharmaceutical ingredient. Placebo will be administered intravenously as a continuous infusion
Sponsors
CalciMedica, Inc.
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen; 2. Moderate ARDS characterized by the following criteria: * Invasive mechanical ventilation with a minimum PEEP of 5 cm H2O; * PaO2/FiO2 ≤200 that may be estimated from pulse oximetry or determined by arterial blood gas; * No evidence of volume overload or heart failure; 3. The patient is ≥18 years of age at the time of consent; 4. QTcF interval ≤ 440 milliseconds; 5. A female patient of childbearing potential must not attempt to become pregnant for 39 months, and if sexually active with a male partner, is willing to practice acceptable methods of birth control for 39 months after the last dose of study drug; 6. A male patient who is sexually active with a female partner of childbearing potential is willing to practice acceptable methods of birth control for 39 months after the last dose of study drug. A male patient must not donate sperm for 39 months; 7. The patient is willing and able to, or has a legal authorized representative (LAR) who is willing and able to, provide informed consent to participate, and to cooperate with all aspects of the protocol.
Exclusion criteria
1. Expected survival or time to withdrawal of life-sustaining treatments expected to be \<7 days. 2. ECMO; 3. Suspected septic shock; 4. The patient has a history of: * Organ or hematologic transplant; * HIV; * Active hepatitis B or hepatitis C infection; 5. Current treatment with: * Chemotherapy; * Immunosuppressive medications or immunotherapy (see Section 5.3 for list of prohibited immunosuppressive medications and immunotherapy) at the time of consent; * Hemodialysis or Peritoneal Dialysis; 6. The patient is known to be pregnant or is nursing; 7. Currently participating in another study of an investigational drug or therapeutic medical device at the time of consent; 8. Allergy to eggs or any of the excipients in study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population. | Baseline Assessment up to 120 hours | Pharmacodynamic endpoint: Assessment of pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets to Auxora treatment. Flow cytometry was performed on fluid collected from the BAL performed prior to the SFISD (-12 hours) and 24 (±12) hours after completing the last infusion of study drug in Cohorts 1 and 2 and during the final 24 hours of the continuous infusion in Cohort 3. The percentage of total WBC population was assessed for the combined CD4, CD8, and monocyte cell population, and the change between Pre- and Post-Infusion samples (Post value minus Pre value) was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent of Immune Cells in BAL Fluid | Baseline Assessment up to 120 hours | Pharmacodynamic endpoint: Assessment of pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets to Auxora treatment. Flow cytometry was performed on fluid collected from the BAL performed prior to the SFISD (-12 hours) and 24 (±12) hours after completing the last infusion of study drug in Cohorts 1 and 2 and during the final 24 hours of the continuous infusion in Cohort 3. The percentage of total WBC population was assessed for immune cell types and the change between Pre- and Post-Infusion samples (Post value minus Pre value) was reported. |
| Number of Patients Alive at Day 60 | Randomization through Day 60 | Efficacy endpoint: All-cause Mortality at Day 60 |
| Number of Days Alive and Out of the Intensive Care Unit (ICU) | From randomization until discharge from ICU, assessed up to 60 days | Efficacy Endpoint: Days in ICU (after randomization) |
| Number of Days Alive and Out of the Hospital | From randomization until discharge from the hospital, assessed up to 60 days | Efficacy endpoint: Days hospitalized (after randomization) |
| Number of Days Alive and Off Mechanical Ventilation | From randomization until patient is extubated, assessed up to 60 days | Efficacy endpoint: Ventilator-free days (after randomization) |
Countries
United States
Participant flow
Pre-assignment details
10 patients were screened, 1 of which did not meet all inclusion/exclusion criteria, resulting in 9 patients randomized. All 9 completed study treatment, and 0 patients withdrew from the study. Patients were randomized 3:1 to Auxora or Placebo. The first 4 patients were enrolled in Cohort 1, and the next 4 in Cohort 2. The next 8 patients were to be enrolled in Cohort 3, but trial terminated early after the first patient was enrolled in Cohort 3, due to lack of new Covid-19 hospitalizations.
Participants by arm
| Arm | Count |
|---|---|
| Auxora Cohort 1 Auxora was given as a continuous infusion:
Day 1: 1.25 mL/kg (2.0 mg/kg) over 4 hours; Day 2: 1.0 mL/kg (1.6 mg/kg) over 4 hours; Day 3: 1.0 mL/kg (1.6 mg/kg) over 4 hours | 3 |
| Auxora Cohort 2 Auxora was given as a continuous infusion:
Day 1: 1.25 mL/kg (2.0 mg/kg) over 4 hours Day 2: 1.25mL/kg (2.0 mg/kg) over 4 hours Day 3: 1.0 mL/kg (1.6 mg/kg) over 4 hours Day 4: 1.0 mL/kg (1.6 mg/kg) over 4 hours | 3 |
| Auxora Cohort 3 Auxora was given as a continuous infusion:
Day 1: Patients initially received 1.25 mL/kg (2.0 mg/kg) over 4 hours; After initial infusion is complete, patients started a continuous infusion of 1.0 mL/kg/24hours for 96 hours (1.6mg/kg/24hours, ending 4 days and 4 hours after the start of first infusion). | 1 |
| Placebo Placebo was given as a continuous infusion, with infusion volume and times matching those of the Auxora Cohort for each respective period.
Day 1: All patients randomized to placebo received 1.25 mL/kg over 4 hours. After initial infusion was complete, patients enrolled during period 3 then received a continuous infusion of 1.0 mL/kg/24 hours for 96 hours.
Day 2: Patients randomized to placebo received 1.0 mL/kg over 4 hours if enrolled during Period 1, or 1.25mL/kg over 4 hours if enrolled during Period 2.
Day 3: Patients randomized to placebo during Periods 1 and 2 received 1.0 mL/kg over 4 hours.
Day 4: Patients randomized to placebo during Period 2 received 1.0 mL/kg over 4 hours. | 2 |
| Total | 9 |
Baseline characteristics
| Characteristic | Auxora Cohort 1 | Auxora Cohort 2 | Auxora Cohort 3 | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.0 years STANDARD_DEVIATION 5.2 | 67.0 years STANDARD_DEVIATION 3 | 46 years | 54 years STANDARD_DEVIATION 1.4 | 57 years STANDARD_DEVIATION 8.4 |
| BMI | 33.2 kg/m^2 STANDARD_DEVIATION 6.6 | 28.9 kg/m^2 STANDARD_DEVIATION 1.6 | 48.9 kg/m^2 | 30.3 kg/m^2 STANDARD_DEVIATION 3.6 | 32.9 kg/m^2 STANDARD_DEVIATION 7.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 170.3 cm STANDARD_DEVIATION 16.6 | 164.7 cm STANDARD_DEVIATION 5.8 | 183 cm | 184.0 cm STANDARD_DEVIATION 12.7 | 172.9 cm STANDARD_DEVIATION 13 |
| Number of Participants with Additional Prior Positive Covid Test No | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Number of Participants with Additional Prior Positive Covid Test Unknown | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Number of Participants with Additional Prior Positive Covid Test Yes | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 7 Participants |
| Number of Participants with Bacterial Superinfection at Intubation | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Number of Participants with Upper Respiratory Co-detection of Sars-CoV-2 | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 1 participants | 2 participants | 9 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 6 Participants |
| Weight | 96.7 kg STANDARD_DEVIATION 26.5 | 78.0 kg STANDARD_DEVIATION 4.4 | 163.4 kg | 103.5 kg STANDARD_DEVIATION 26.2 | 99.4 kg STANDARD_DEVIATION 30.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 7 | 2 / 3 | 2 / 3 | 0 / 1 | 1 / 2 |
| other Total, other adverse events | 7 / 7 | 3 / 3 | 3 / 3 | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 4 / 7 | 1 / 3 | 3 / 3 | 0 / 1 | 2 / 2 |
Outcome results
Primary
Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population.
Pharmacodynamic endpoint: Assessment of pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets to Auxora treatment. Flow cytometry was performed on fluid collected from the BAL performed prior to the SFISD (-12 hours) and 24 (±12) hours after completing the last infusion of study drug in Cohorts 1 and 2 and during the final 24 hours of the continuous infusion in Cohort 3. The percentage of total WBC population was assessed for the combined CD4, CD8, and monocyte cell population, and the change between Pre- and Post-Infusion samples (Post value minus Pre value) was reported.
Time frame: Baseline Assessment up to 120 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Auxora Cohort 1 | Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population. | -5.6 Percent of total WBC population | Standard Deviation 31.6 |
| Auxora Cohort 2 | Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population. | -7.2 Percent of total WBC population | Standard Deviation 10.7 |
| Auxora Cohort 3 | Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population. | 27.1 Percent of total WBC population | — |
| Placebo | Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population. | 22.8 Percent of total WBC population | Standard Deviation 9.7 |
Secondary
Change From Baseline in Percent of Immune Cells in BAL Fluid
Pharmacodynamic endpoint: Assessment of pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets to Auxora treatment. Flow cytometry was performed on fluid collected from the BAL performed prior to the SFISD (-12 hours) and 24 (±12) hours after completing the last infusion of study drug in Cohorts 1 and 2 and during the final 24 hours of the continuous infusion in Cohort 3. The percentage of total WBC population was assessed for immune cell types and the change between Pre- and Post-Infusion samples (Post value minus Pre value) was reported.
Time frame: Baseline Assessment up to 120 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Auxora Cohort 1 | Change From Baseline in Percent of Immune Cells in BAL Fluid | B cells | 14.2 Percent of total WBC population | Standard Deviation 10.4 |
| Auxora Cohort 1 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Macrophages | 6.3 Percent of total WBC population | Standard Deviation 20 |
| Auxora Cohort 1 | Change From Baseline in Percent of Immune Cells in BAL Fluid | CD8 T Cells | -2.0 Percent of total WBC population | Standard Deviation 12.5 |
| Auxora Cohort 1 | Change From Baseline in Percent of Immune Cells in BAL Fluid | NK cells | -0.2 Percent of total WBC population | Standard Deviation 1.5 |
| Auxora Cohort 1 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Monocytes | -1.2 Percent of total WBC population | Standard Deviation 10 |
| Auxora Cohort 1 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Neutrophils | -14.5 Percent of total WBC population | Standard Deviation 43.9 |
| Auxora Cohort 1 | Change From Baseline in Percent of Immune Cells in BAL Fluid | CD4 T Cells | -2.4 Percent of total WBC population | Standard Deviation 15.7 |
| Auxora Cohort 2 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Neutrophils | 24.4 Percent of total WBC population | Standard Deviation 47.1 |
| Auxora Cohort 2 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Monocytes | -3.3 Percent of total WBC population | Standard Deviation 5.8 |
| Auxora Cohort 2 | Change From Baseline in Percent of Immune Cells in BAL Fluid | CD8 T Cells | -0.5 Percent of total WBC population | Standard Deviation 4.6 |
| Auxora Cohort 2 | Change From Baseline in Percent of Immune Cells in BAL Fluid | NK cells | -1.8 Percent of total WBC population | Standard Deviation 1.5 |
| Auxora Cohort 2 | Change From Baseline in Percent of Immune Cells in BAL Fluid | CD4 T Cells | -3.4 Percent of total WBC population | Standard Deviation 6.3 |
| Auxora Cohort 2 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Macrophages | -2.3 Percent of total WBC population | Standard Deviation 23.1 |
| Auxora Cohort 2 | Change From Baseline in Percent of Immune Cells in BAL Fluid | B cells | -12.4 Percent of total WBC population | Standard Deviation 14.3 |
| Auxora Cohort 3 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Neutrophils | -4.2 Percent of total WBC population | — |
| Auxora Cohort 3 | Change From Baseline in Percent of Immune Cells in BAL Fluid | CD4 T Cells | 5.9 Percent of total WBC population | — |
| Auxora Cohort 3 | Change From Baseline in Percent of Immune Cells in BAL Fluid | NK cells | 0.1 Percent of total WBC population | — |
| Auxora Cohort 3 | Change From Baseline in Percent of Immune Cells in BAL Fluid | CD8 T Cells | 23.1 Percent of total WBC population | — |
| Auxora Cohort 3 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Monocytes | -13.4 Percent of total WBC population | — |
| Auxora Cohort 3 | Change From Baseline in Percent of Immune Cells in BAL Fluid | B cells | 3.2 Percent of total WBC population | — |
| Auxora Cohort 3 | Change From Baseline in Percent of Immune Cells in BAL Fluid | Macrophages | -3.8 Percent of total WBC population | — |
| Placebo | Change From Baseline in Percent of Immune Cells in BAL Fluid | CD8 T Cells | 5.3 Percent of total WBC population | Standard Deviation 3.9 |
| Placebo | Change From Baseline in Percent of Immune Cells in BAL Fluid | Macrophages | 25.2 Percent of total WBC population | Standard Deviation 16.9 |
| Placebo | Change From Baseline in Percent of Immune Cells in BAL Fluid | B cells | -23.2 Percent of total WBC population | Standard Deviation 29.9 |
| Placebo | Change From Baseline in Percent of Immune Cells in BAL Fluid | Monocytes | -0.4 Percent of total WBC population | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Percent of Immune Cells in BAL Fluid | NK cells | 0.3 Percent of total WBC population | Standard Deviation 1.3 |
| Placebo | Change From Baseline in Percent of Immune Cells in BAL Fluid | CD4 T Cells | 17.9 Percent of total WBC population | Standard Deviation 5.4 |
| Placebo | Change From Baseline in Percent of Immune Cells in BAL Fluid | Neutrophils | -25.7 Percent of total WBC population | Standard Deviation 24 |
Secondary
Number of Days Alive and Off Mechanical Ventilation
Efficacy endpoint: Ventilator-free days (after randomization)
Time frame: From randomization until patient is extubated, assessed up to 60 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Auxora Cohort 1 | Number of Days Alive and Off Mechanical Ventilation | 5.9 days | Standard Deviation 10.2 |
| Auxora Cohort 2 | Number of Days Alive and Off Mechanical Ventilation | 8.0 days | Standard Deviation 13.9 |
| Auxora Cohort 3 | Number of Days Alive and Off Mechanical Ventilation | 0 days | Standard Deviation 0 |
| Placebo | Number of Days Alive and Off Mechanical Ventilation | 17.0 days | — |
| Placebo | Number of Days Alive and Off Mechanical Ventilation | 0 days | Standard Deviation 0 |
Secondary
Number of Days Alive and Out of the Hospital
Efficacy endpoint: Days hospitalized (after randomization)
Time frame: From randomization until discharge from the hospital, assessed up to 60 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Auxora Cohort 1 | Number of Days Alive and Out of the Hospital | 1.0 days | Standard Deviation 2.6 |
| Auxora Cohort 2 | Number of Days Alive and Out of the Hospital | 0 days | Standard Deviation 0 |
| Auxora Cohort 3 | Number of Days Alive and Out of the Hospital | 0 days | Standard Deviation 0 |
| Placebo | Number of Days Alive and Out of the Hospital | 7.0 days | — |
| Placebo | Number of Days Alive and Out of the Hospital | 0 days | Standard Deviation 0 |
Secondary
Number of Days Alive and Out of the Intensive Care Unit (ICU)
Efficacy Endpoint: Days in ICU (after randomization)
Time frame: From randomization until discharge from ICU, assessed up to 60 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Auxora Cohort 1 | Number of Days Alive and Out of the Intensive Care Unit (ICU) | 4.6 days | Standard Deviation 8 |
| Auxora Cohort 2 | Number of Days Alive and Out of the Intensive Care Unit (ICU) | 6.3 days | Standard Deviation 11 |
| Auxora Cohort 3 | Number of Days Alive and Out of the Intensive Care Unit (ICU) | 0 days | Standard Deviation 0 |
| Placebo | Number of Days Alive and Out of the Intensive Care Unit (ICU) | 13.0 days | — |
| Placebo | Number of Days Alive and Out of the Intensive Care Unit (ICU) | 0 days | Standard Deviation 0 |
Secondary
Number of Patients Alive at Day 60
Efficacy endpoint: All-cause Mortality at Day 60
Time frame: Randomization through Day 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auxora Cohort 1 | Number of Patients Alive at Day 60 | 3 Participants |
| Auxora Cohort 2 | Number of Patients Alive at Day 60 | 1 Participants |
| Auxora Cohort 3 | Number of Patients Alive at Day 60 | 1 Participants |
| Placebo | Number of Patients Alive at Day 60 | 1 Participants |
| Placebo | Number of Patients Alive at Day 60 | 1 Participants |
Other Pre-specified
Intensity of AEs
Safety endpoint: Count of the number of AEs for each level of intensity: mild, moderate, or severe
Time frame: Randomization through Day 30
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Auxora Cohort 1 | Intensity of AEs | Moderate | 21 Adverse Events |
| Auxora Cohort 1 | Intensity of AEs | Mild | 13 Adverse Events |
| Auxora Cohort 1 | Intensity of AEs | Severe | 8 Adverse Events |
| Auxora Cohort 2 | Intensity of AEs | Moderate | 11 Adverse Events |
| Auxora Cohort 2 | Intensity of AEs | Mild | 2 Adverse Events |
| Auxora Cohort 2 | Intensity of AEs | Severe | 2 Adverse Events |
| Auxora Cohort 3 | Intensity of AEs | Severe | 6 Adverse Events |
| Auxora Cohort 3 | Intensity of AEs | Mild | 9 Adverse Events |
| Auxora Cohort 3 | Intensity of AEs | Moderate | 8 Adverse Events |
| Placebo | Intensity of AEs | Severe | 0 Adverse Events |
| Placebo | Intensity of AEs | Moderate | 2 Adverse Events |
| Placebo | Intensity of AEs | Mild | 2 Adverse Events |
| Placebo | Intensity of AEs | Moderate | 7 Adverse Events |
| Placebo | Intensity of AEs | Severe | 2 Adverse Events |
| Placebo | Intensity of AEs | Mild | 5 Adverse Events |
Other Pre-specified
Number of Patients Experiencing an AE Considered Possibly Related to Study Drug
Safety endpoint. Examines the relatedness of AEs to study drug by assessing the number of patients experiencing any AE (serious or non-serious) considered possibly related to Study Drug.
Time frame: Randomization through Day 30
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Auxora Cohort 1 | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related non-serious AEs | 2 Participants |
| Auxora Cohort 1 | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related SAEs | 0 Participants |
| Auxora Cohort 2 | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related non-serious AEs | 1 Participants |
| Auxora Cohort 2 | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related SAEs | 0 Participants |
| Auxora Cohort 3 | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related SAEs | 0 Participants |
| Auxora Cohort 3 | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related non-serious AEs | 0 Participants |
| Placebo | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related SAEs | 0 Participants |
| Placebo | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related non-serious AEs | 1 Participants |
| Placebo | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related SAEs | 0 Participants |
| Placebo | Number of Patients Experiencing an AE Considered Possibly Related to Study Drug | Possibly related non-serious AEs | 0 Participants |
Other Pre-specified
Number of Patients Experiencing an SAE (at Least 1)
Safety Endpoint: Incidence of treatment emergent Serious Adverse Events (SAEs)
Time frame: Randomization through day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auxora Cohort 1 | Number of Patients Experiencing an SAE (at Least 1) | 4 Participants |
| Auxora Cohort 2 | Number of Patients Experiencing an SAE (at Least 1) | 1 Participants |
| Auxora Cohort 3 | Number of Patients Experiencing an SAE (at Least 1) | 3 Participants |
| Placebo | Number of Patients Experiencing an SAE (at Least 1) | 0 Participants |
| Placebo | Number of Patients Experiencing an SAE (at Least 1) | 2 Participants |
Other Pre-specified
Number of Patients Experiencing Pre-defined Changes in Cardiac Conduction Assessed by ECG
Safety endpoint: Patients experiencing Changes in cardiac conduction, defined as: QTcF interval of ≥ 500 msec; QTcF prolongation of ≥ 60 msec as compared to baseline; Mobitz Type II second degree atrioventricular (AV) block; Third degree or high grade AV block; or Polymorphic Ventricular Tachycardia
Time frame: From randomization up to 144 hours after SFISD (start of first infusion of study drug)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auxora Cohort 1 | Number of Patients Experiencing Pre-defined Changes in Cardiac Conduction Assessed by ECG | 0 Participants |
| Auxora Cohort 2 | Number of Patients Experiencing Pre-defined Changes in Cardiac Conduction Assessed by ECG | 0 Participants |
| Auxora Cohort 3 | Number of Patients Experiencing Pre-defined Changes in Cardiac Conduction Assessed by ECG | 0 Participants |
| Placebo | Number of Patients Experiencing Pre-defined Changes in Cardiac Conduction Assessed by ECG | 0 Participants |
| Placebo | Number of Patients Experiencing Pre-defined Changes in Cardiac Conduction Assessed by ECG | 0 Participants |