Covid-19
Conditions
Keywords
SARS-CoV-2, Covid, Coronavirus, Covid19, COVID-19
Brief summary
This is a phase 3, randomized, placebo controlled, double-blind, multicenter, stratified study of CPI-006 plus standard of care (SOC) versus placebo plus SOC in mild to moderately symptomatic hospitalized Covid-19 patients with the primary objective to compare the proportion of participants alive and respiratory failure free between CPI-006 plus SOC versus placebo plus SOC.
Interventions
DRUGCPI-006 2 mg/kg + SOC
IV CPI-006 2 mg/kg up to a maximum dose of 200 mg plus standard of care
DRUGCPI-006 1 mg/kg + SOC
IV CPI-006 1 mg/kg up to a maximum dose of 100 mg plus standard of care
DRUGPlacebo + SOC
IV placebo plus standard of care
Sponsors
Corvus Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed positive by polymerase chain reaction (PCR) or antigen test for SARS-CoV-2 with sample collection ≤ 10 days prior to randomization * Covid-19 illness of any duration of symptoms * Hospitalized for Covid-19 for ≤ 5 days with mild to moderate Covid-19 symptoms and meets criteria for either Category 4, Category 5, or Category 6 per 8-point ordinal scale * Adequate organ function * Participants of child-bearing age must agree to use adequate contraception for 6 weeks after study treatment administration
Exclusion criteria
* Signs of acute respiratory distress syndrome or respiratory failure necessitating mechanical ventilation at time of screening/randomization or anticipated need for mechanical ventilation * History of severe chronic respiratory disease and requirement for long-term oxygen therapy * Uncontrolled active systemic infection or hemodynamic instability requiring admission to an intensive care unit * Malignant tumor receiving treatment, or other serious systemic diseases affecting life expectancy within 29 days of screening * Receipt of cancer chemotherapy or immunomodulatory drugs during preceding 2 months (steroids for treatment of Covid-19 are acceptable) * Convalescent plasma (CCP) or anti-SARS-CoV-2 monoclonal antibodies administered \<24 hours prior to randomization. Must have recovered from any adverse events related to CCP treatment. Received chloroquine or hydroxychloroquine within last 7 days or during the study * Current participation in other clinical trials including extended access programs * Active deep vein thrombosis or pulmonary embolism within last 6 months * Anticipated discharge from hospital or transfer to another hospital which is not a study site within 48 hours of admission * Active uncontrolled co-morbid disease that may interfere with study conduct or interpretation of findings * Known to be positive for HIV or positive test for chronic HBV infection or positive test for hepatitis C antibody * Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Alive and Respiratory Failure Free of CPI-006 Plus SOC Versus Placebo Plus SOC | During the 28 days after dosing | Proportion of participants who are alive and free from respiratory deterioration in each active arm compared to placebo arm as measured by the modified World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement in which: 1=Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requiring ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Covid-19 related or otherwise); 5=Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 8=Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recovery of CPI-006 Plus SOC Versus Placebo Plus SOC | During the 28 days after dosing | Time to recovery after dosing in each active arm compared to placebo arm as measured by the modified WHO 8-point Ordinal Scale for Clinical Improvement in which: 1=Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requiring ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Covid-19 related or otherwise); 5=Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 8=Death. |
| Time to Clinical Improvement of CPI-006 Plus SOC Versus Placebo Plus SOC | During the 28 days after dosing | Time to clinical improvement in each active arm compared to placebo arm as measured by the modified WHO 8-point Ordinal Scale for Clinical Improvement in which: 1=Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requiring ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Covid-19 related or otherwise); 5=Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 8=Death. Clinical improvement is defined as ≥ 2 points improvement in the 8-point ordinal scale. |
| Mortality Rate Due to Any Cause of CPI-006 Plus SOC Versus Placebo Plus SOC | During the 28 days after dosing | Proportion of participants who died in each active arm compared to placebo arm |
Countries
Argentina, Brazil, Canada, Chile, Colombia, Germany, Italy, Mexico, Peru, Spain, Ukraine, United States
Participant flow
Recruitment details
46 participants were screened and 42 were randomized. Of the 42 participants randomized, only 40 received the treatment assigned at randomization (2 were randomized but withdrew consent prior to receiving study treatment).
Participants by arm
| Arm | Count |
|---|---|
| Treatment A: CPI-006 2 mg/kg + SOC IV CPI-006 2 mg/kg up to a maximum dose of 200 mg on Day 1 plus standard of care | 16 |
| Treatment B: CPI-006 1 mg/kg + SOC IV CPI-006 1 mg/kg up to a maximum dose of 100 mg on Day 1 plus standard of care | 14 |
| Treatment C: Placebo + SOC IV placebo on Day 1 plus standard of care | 12 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 | 2 |
| Overall Study | Randomized but not dosed | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Treatment C: Placebo + SOC | Treatment B: CPI-006 1 mg/kg + SOC | Treatment A: CPI-006 2 mg/kg + SOC |
|---|---|---|---|---|
| 8-point Ordinal Scale Assessment 4 | 5 Participants | 2 Participants | 3 Participants | 0 Participants |
| 8-point Ordinal Scale Assessment 5 | 24 Participants | 7 Participants | 10 Participants | 7 Participants |
| 8-point Ordinal Scale Assessment 6 | 13 Participants | 3 Participants | 1 Participants | 9 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 12 Participants | 13 Participants | 13 Participants |
| Age, Continuous | 56.0 years | 55.0 years | 53.0 years | 56.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 8 Participants | 11 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 33 Participants | 9 Participants | 11 Participants | 13 Participants |
| Region of Enrollment Spain | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 41 Participants | 12 Participants | 13 Participants | 16 Participants |
| Sex: Female, Male Female | 18 Participants | 9 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 24 Participants | 3 Participants | 11 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 | 0 / 11 |
| other Total, other adverse events | 5 / 15 | 2 / 14 | 2 / 11 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 2 / 11 |
Outcome results
Primary
Proportion of Participants Alive and Respiratory Failure Free of CPI-006 Plus SOC Versus Placebo Plus SOC
Proportion of participants who are alive and free from respiratory deterioration in each active arm compared to placebo arm as measured by the modified World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement in which: 1=Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requiring ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Covid-19 related or otherwise); 5=Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 8=Death.
Time frame: During the 28 days after dosing
Population: All participants who received any amount of study drug (CPI-006 or placebo) and have post-baseline efficacy assessment based on the 8-point ordinal scale.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: CPI-006 2 mg/kg + SOC | Proportion of Participants Alive and Respiratory Failure Free of CPI-006 Plus SOC Versus Placebo Plus SOC | 14 Participants |
| Treatment B: CPI-006 1 mg/kg + SOC | Proportion of Participants Alive and Respiratory Failure Free of CPI-006 Plus SOC Versus Placebo Plus SOC | 12 Participants |
| Treatment C: Placebo + SOC | Proportion of Participants Alive and Respiratory Failure Free of CPI-006 Plus SOC Versus Placebo Plus SOC | 9 Participants |
Secondary
Mortality Rate Due to Any Cause of CPI-006 Plus SOC Versus Placebo Plus SOC
Proportion of participants who died in each active arm compared to placebo arm
Time frame: During the 28 days after dosing
Population: All participants who received any amount of study drug (CPI-006 or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: CPI-006 2 mg/kg + SOC | Mortality Rate Due to Any Cause of CPI-006 Plus SOC Versus Placebo Plus SOC | 0 Participants |
| Treatment B: CPI-006 1 mg/kg + SOC | Mortality Rate Due to Any Cause of CPI-006 Plus SOC Versus Placebo Plus SOC | 0 Participants |
| Treatment C: Placebo + SOC | Mortality Rate Due to Any Cause of CPI-006 Plus SOC Versus Placebo Plus SOC | 0 Participants |
Secondary
Time to Clinical Improvement of CPI-006 Plus SOC Versus Placebo Plus SOC
Time to clinical improvement in each active arm compared to placebo arm as measured by the modified WHO 8-point Ordinal Scale for Clinical Improvement in which: 1=Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requiring ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Covid-19 related or otherwise); 5=Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 8=Death. Clinical improvement is defined as ≥ 2 points improvement in the 8-point ordinal scale.
Time frame: During the 28 days after dosing
Population: All participants who received any amount of study drug (CPI-006 or placebo) and achieved clinical improvement during the 28 days after dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: CPI-006 2 mg/kg + SOC | Time to Clinical Improvement of CPI-006 Plus SOC Versus Placebo Plus SOC | 6.0 days |
| Treatment B: CPI-006 1 mg/kg + SOC | Time to Clinical Improvement of CPI-006 Plus SOC Versus Placebo Plus SOC | 4.5 days |
| Treatment C: Placebo + SOC | Time to Clinical Improvement of CPI-006 Plus SOC Versus Placebo Plus SOC | 7.0 days |
Secondary
Time to Recovery of CPI-006 Plus SOC Versus Placebo Plus SOC
Time to recovery after dosing in each active arm compared to placebo arm as measured by the modified WHO 8-point Ordinal Scale for Clinical Improvement in which: 1=Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requiring ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Covid-19 related or otherwise); 5=Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 8=Death.
Time frame: During the 28 days after dosing
Population: All participants who received any amount of study drug (CPI-006 or placebo) and recovered during the 28 days after dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: CPI-006 2 mg/kg + SOC | Time to Recovery of CPI-006 Plus SOC Versus Placebo Plus SOC | 6.0 days |
| Treatment B: CPI-006 1 mg/kg + SOC | Time to Recovery of CPI-006 Plus SOC Versus Placebo Plus SOC | 4.5 days |
| Treatment C: Placebo + SOC | Time to Recovery of CPI-006 Plus SOC Versus Placebo Plus SOC | 7.0 days |