COVID-19
Conditions
Keywords
Severe Acute Respiratory Syndrome coronavirus, SARS-COV-2 infection
Brief summary
This study evaluates the efficacy and safety of intravenous (IV) infusions of pamrevlumab when compared with placebo in participants who are hospitalized with acute COVID-19 disease.
Detailed description
This is a randomized, double-blind, placebo-controlled, phase 2, proof-of-concept study to evaluate the efficacy and safety of IV pamrevlumab, a monoclonal antibody, against connective-tissue growth factor (CTGF), in participants hospitalized with acute COVID-19 disease. All concomitant medications, including approved and non-approved treatments for COVID-19 (such as, hydroxychloroquine or interleukin 6 \[IL-6\] inhibitors), as well as supplemental oxygenation needs, will be collected and recorded. In addition, the following will be collected and recorded: documentation of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov-2) infection, documentation of any other infection(s) prior to or during hospitalization, and whether or not aggressive care is withheld or withdrawn, including the reason for withholding or withdrawal of care (such as a Do Not Resuscitate/Do Not Intubate \[DNR/DNI\] order or a resource limitation).
Interventions
DRUGPamrevlumab
Sterile liquid for injection
DRUGPlacebo
Sterile liquid for injection
Sponsors
Kyntra Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Proof-of-concept
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Confirmed SARS-CoV-2 infection 2. Respiratory compromise requiring hospitalization for COVID-19 disease as evidenced by at least one (or more) of the following criteria: * Interstitial pneumonia on chest x-ray or high-resolution computed tomography (findings of consolidation or ground glass opacities), OR * Peripheral capillary oxygen saturation \< 94% on room air, OR * Requiring non-invasive supplemental oxygen (such as, nasal cannula, face mask) to maintain SpO2 3. Not requiring mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) use at time of randomization 4. Not participating in another clinical trial for the treatment of COVID-19 disease through Day 28
Exclusion criteria
1. Female participants who are pregnant or nursing 2. Participation in a clinical trial with another investigational drug for COVID-19 disease 3. Anticipated discharge from the hospital or transfer to another hospital or long-term care facility which is not a study site within 72 hours of randomization 4. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Alive Who Never Received Mechanical Ventilation and/or Extracorporeal Membrane Oxygenation (ECMO) at Day 28 | Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Alive Who Never Received Mechanical Ventilation and/or ECMO at Day 14 | Day 14 | — |
| Time to Recovery as Based on a Modified 8-Point Ordinal Scale | Day 28 | Recovery was defined as the first day on which the participant satisfied 1 of the following 3 categories from the 8-point ordinal scale: (1) hospitalized, not requiring supplemental oxygen; (2) Not hospitalized (discharged), but with limitation on activities and/or requiring home supplemental oxygen; (3) Not hospitalized (discharged), with no limitations on activities and not requiring supplemental oxygen). |
| Days in Intensive Care Unit/Critical Care Unit (ICU/CCU) (Either on or Off Mechanical Ventilation and/or ECMO) | up to Day 28 | Days in ICU/CCU was calculated as Event end date/time - Event start data/time + 1. Participants who died in ICU/CCU before Day 28, days in ICU/CCU is calculated up to the death date. Days in ICU/CCU were censored after Day 28. |
| Days on Mechanical Ventilation and/or ECMO | up to Day 28 | Days on Mechanical Ventilation and/or ECMO was calculated as Event end date/time - Event start data/time. Participants who died on MV/ECMO before Day 28, days on MV/ECMO is calculated up to the death date. Days on MV/ECMO are censored after Day 28. |
| Time to Mechanical Ventilation/ECMO or All-cause Mortality | up to Day 28 | Time (number of days) from randomization to mechanical ventilation/ECMO or all-cause mortality by Day 28. Participants without the event are not included in the calculation. |
| Number of Participants Alive, Discharged Home, and Not on Supplemental Oxygen at Day 28 | Day 28 | — |
| Changes in Pressure of Arterial Oxygen to Fractional Inspired Oxygen Concentration (PaO2/FiO2) Ratio, Both as Categorical and Continuous Variables | up to Day 28 | — |
| Time to Death From Any Cause | up to Day 28 | Time (number of days) from randomization to death from any cause by Day 28. Participants without the event are not included in the calculation. |
| Change in Resting Peripheral Oxygen Saturation (SpO2) Adjusted by FiO2 | up to Day 28 | — |
| Change in (Non-invasive) Oxygen Supplementation Requirements | up to Day 28 | — |
| Number of Participants With All-cause Mortality | up to Day 28 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pamrevlumab Pamrevlumab: 35 milligrams/kilogram (mg/kg) on Days 1, 7, 14 and 28 for a total of 4 infusions over 4 weeks | 11 |
| Placebo Pamrevlumab-matching placebo on Days 1, 7, 14 and 28 for a total of 4 infusions over 4 weeks | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other than specified | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Pamrevlumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 61 years STANDARD_DEVIATION 10 | 61 years STANDARD_DEVIATION 14 | 61 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 8 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 11 | 2 / 11 |
| other Total, other adverse events | 4 / 9 | 8 / 11 |
| serious Total, serious adverse events | 5 / 9 | 2 / 11 |
Outcome results
Primary
Number of Participants Alive Who Never Received Mechanical Ventilation and/or Extracorporeal Membrane Oxygenation (ECMO) at Day 28
Time frame: Day 28
Population: ITT Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pamrevlumab | Number of Participants Alive Who Never Received Mechanical Ventilation and/or Extracorporeal Membrane Oxygenation (ECMO) at Day 28 | 8 Participants |
| Placebo | Number of Participants Alive Who Never Received Mechanical Ventilation and/or Extracorporeal Membrane Oxygenation (ECMO) at Day 28 | 9 Participants |
Secondary
Change in (Non-invasive) Oxygen Supplementation Requirements
Time frame: up to Day 28
Population: Due to early termination of the study, data was not collected for the assessment.
Secondary
Change in Resting Peripheral Oxygen Saturation (SpO2) Adjusted by FiO2
Time frame: up to Day 28
Population: Due to early termination of the study, data was not collected for the assessment.
Secondary
Changes in Pressure of Arterial Oxygen to Fractional Inspired Oxygen Concentration (PaO2/FiO2) Ratio, Both as Categorical and Continuous Variables
Time frame: up to Day 28
Population: Due to early termination of the study, data was not collected for the assessment.
Secondary
Days in Intensive Care Unit/Critical Care Unit (ICU/CCU) (Either on or Off Mechanical Ventilation and/or ECMO)
Days in ICU/CCU was calculated as Event end date/time - Event start data/time + 1. Participants who died in ICU/CCU before Day 28, days in ICU/CCU is calculated up to the death date. Days in ICU/CCU were censored after Day 28.
Time frame: up to Day 28
Population: ITT Population: All randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pamrevlumab | Days in Intensive Care Unit/Critical Care Unit (ICU/CCU) (Either on or Off Mechanical Ventilation and/or ECMO) | 16 days | Standard Deviation 14 |
| Placebo | Days in Intensive Care Unit/Critical Care Unit (ICU/CCU) (Either on or Off Mechanical Ventilation and/or ECMO) | 12 days | Standard Deviation 17 |
Secondary
Days on Mechanical Ventilation and/or ECMO
Days on Mechanical Ventilation and/or ECMO was calculated as Event end date/time - Event start data/time. Participants who died on MV/ECMO before Day 28, days on MV/ECMO is calculated up to the death date. Days on MV/ECMO are censored after Day 28.
Time frame: up to Day 28
Population: ITT Population: All randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pamrevlumab | Days on Mechanical Ventilation and/or ECMO | 20.5 days | Standard Deviation 0 |
| Placebo | Days on Mechanical Ventilation and/or ECMO | 8.7 days | Standard Deviation 11.1 |
Secondary
Number of Participants Alive, Discharged Home, and Not on Supplemental Oxygen at Day 28
Time frame: Day 28
Population: ITT Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pamrevlumab | Number of Participants Alive, Discharged Home, and Not on Supplemental Oxygen at Day 28 | 6 Participants |
| Placebo | Number of Participants Alive, Discharged Home, and Not on Supplemental Oxygen at Day 28 | 7 Participants |
Secondary
Number of Participants Alive Who Never Received Mechanical Ventilation and/or ECMO at Day 14
Time frame: Day 14
Population: ITT Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pamrevlumab | Number of Participants Alive Who Never Received Mechanical Ventilation and/or ECMO at Day 14 | 8 Participants |
| Placebo | Number of Participants Alive Who Never Received Mechanical Ventilation and/or ECMO at Day 14 | 9 Participants |
Secondary
Number of Participants With All-cause Mortality
Time frame: up to Day 28
Population: ITT Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pamrevlumab | Number of Participants With All-cause Mortality | 2 Participants |
| Placebo | Number of Participants With All-cause Mortality | 1 Participants |
Secondary
Time to Death From Any Cause
Time (number of days) from randomization to death from any cause by Day 28. Participants without the event are not included in the calculation.
Time frame: up to Day 28
Population: ITT Population: All randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pamrevlumab | Time to Death From Any Cause | 17 days | Standard Deviation 15 |
| Placebo | Time to Death From Any Cause | 13 days | — |
Secondary
Time to Mechanical Ventilation/ECMO or All-cause Mortality
Time (number of days) from randomization to mechanical ventilation/ECMO or all-cause mortality by Day 28. Participants without the event are not included in the calculation.
Time frame: up to Day 28
Population: ITT Population: All randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pamrevlumab | Time to Mechanical Ventilation/ECMO or All-cause Mortality | 14 days | Standard Deviation 11 |
| Placebo | Time to Mechanical Ventilation/ECMO or All-cause Mortality | 14 days | Standard Deviation 1 |
Secondary
Time to Recovery as Based on a Modified 8-Point Ordinal Scale
Recovery was defined as the first day on which the participant satisfied 1 of the following 3 categories from the 8-point ordinal scale: (1) hospitalized, not requiring supplemental oxygen; (2) Not hospitalized (discharged), but with limitation on activities and/or requiring home supplemental oxygen; (3) Not hospitalized (discharged), with no limitations on activities and not requiring supplemental oxygen).
Time frame: Day 28
Population: ITT Population: All randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pamrevlumab | Time to Recovery as Based on a Modified 8-Point Ordinal Scale | 11 days | Standard Deviation 10 |
| Placebo | Time to Recovery as Based on a Modified 8-Point Ordinal Scale | 11 days | Standard Deviation 12 |