A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MSTT1041A or UTTR1147A in Patients With Severe COVID-19 Pneumonia
Overview
- Phase
- Phase 2
- Intervention
- MSTT1041A-matched Placebo
- Conditions
- COVID-19 Pneumonia
- Sponsor
- Genentech, Inc.
- Enrollment
- 396
- Locations
- 41
- Primary Endpoint
- Time to Recovery, Defined as the Time to a Clinical Status Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First) by Day 28
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a Phase II, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of MSTT1041A (astegolimab) compared with placebo and of UTTR1147A compared with placebo, in combination with standard of care (SOC), in patients hospitalized with severe coronavirus disease 2019 (COVID-19) pneumonia.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Hospitalized with COVID-19 pneumonia confirmed per WHO criteria (including a positive PCR of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan
- •Peripheral capillary oxygen saturation (SpO2) ≤93% (on room air or supplemental oxygen) or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤300 millimetres of mercury (mmHg) or requiring supplemental oxygen to maintain SpO2 \>93% or requirement for supplemental oxygen to maintain SpO2 at an acceptable level per local standard of care
Exclusion Criteria
- •Pregnant or breastfeeding, or positive pregnancy test at screening
- •Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
- •In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
- •Participating in another clinical drug trial
- •Treatment with investigational therapy (other than for COVID-19) within 5 half-lives or 30 days (whichever is longer) prior to initiation of study drug
- •Use of Janus kinase (JAK) inhibitor within 30 days or 5 drug elimination half-lives (whichever is longer) prior to screening
- •Have received high-dose systemic corticosteroids (≥1 mg/kg/day methylprednisolone or equivalent) within 72 hours prior to Day 1
- •Known HIV infection with CD4 \<200 cells/microlitre (uL) or \<14% of all lymphocytes
- •ALT or AST \>10 times the upper limit of normal (ULN) detected at screening
- •History of anaplastic large-cell lymphoma or mantle-cell lymphoma
Arms & Interventions
All Placebo
Participants randomized to this arm received one intravenous (IV) infusion of either MSTT1041A-matched placebo or UTTR1147A-matched placebo on Day 1. A second IV infusion of either MSTT1041A-matched placebo or UTTR1147A-matched placebo (same placebo as the first infusion) was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen. Study treatment was given in combination with the standard of care for COVID-19 pneumonia.
Intervention: MSTT1041A-matched Placebo
All Placebo
Participants randomized to this arm received one intravenous (IV) infusion of either MSTT1041A-matched placebo or UTTR1147A-matched placebo on Day 1. A second IV infusion of either MSTT1041A-matched placebo or UTTR1147A-matched placebo (same placebo as the first infusion) was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen. Study treatment was given in combination with the standard of care for COVID-19 pneumonia.
Intervention: UTTR1147A-matched Placebo
MSTT1041A
Participants randomized to this arm received one intravenous (IV) infusion of MSTT1041A 700 milligrams (mg) on Day 1. A second IV dose of MSTT1041A 350 mg was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen. Study treatment was given in combination with the standard of care for COVID-19 pneumonia.
Intervention: MSTT1041A
UTTR1147A
Participants randomized to this arm received one intravenous (IV) infusion of UTTR1147A 90 micrograms/kilogram body weight (μg/kg) on Day 1. A second IV dose of UTTR1147A 90 μg/kg was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen. Study treatment was given in combination with the standard of care for COVID-19 pneumonia.
Intervention: UTTR1147A
Outcomes
Primary Outcomes
Time to Recovery, Defined as the Time to a Clinical Status Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First) by Day 28
Time Frame: From Baseline up to 28 days
The time to recovery was defined as the time from baseline to a clinical status score of 1 or 2 on the 7-category ordinal scale (whichever occurs first); clinical status scores are defined as follows: 1. Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; 3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death.
Secondary Outcomes
- Duration of Supplemental Oxygen by Day 28(Up to 28 days)
- Clinical Status Score at Day 14, Assessed Using a 7-Category Ordinal Scale(Day 14)
- Percentage of Participants Needing Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Day 28(Up to 28 days)
- Number of Ventilator-Free Days by Day 28(Up to 28 days)
- Percentage of Participants With an Intensive Care Unit (ICU) Stay by Day 28(Up to 28 days)
- Percentage of Participants Alive and Free of Respiratory Failure by Day 28(Up to 28 days)
- Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status by Day 28(From Baseline up to 28 days)
- Time to Hospital Discharge or "Ready for Discharge" by Day 28(Up to 28 days)
- Clinical Status Score at Day 28, Assessed Using a 7-Category Ordinal Scale(Day 28)
- Duration of Intensive Care Unit (ICU) Stay by Day 28(Up to 28 days)
- Time to Clinical Failure by Day 28, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First)(Up to 28 days)
- Percentage of Participants Who Died by Day 14(Up to Day 14)
- Percentage of Participants Who Died by Day 28(Up to Day 28)
- Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) Aggregate Score of ≤2 Maintained for 24 Hours(Up to 28 days)
- Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)(From Baseline until study completion/discontinuation (up to 60 days))
- Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline(From Baseline up to 60 days)
- Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints(Baseline, Days 14 and 28, Discharge Day (up to Day 28), and Study Completion Visit (up to Day 60))
- Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline(At Baseline (pre-dose on Day 1) and post-baseline (Days 15 and 28; and discharge day and study completion [up to 60 days]))
- Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline(From Baseline up to 60 days)
- Serum Concentration of MSTT1041A at Specified Timepoints(For the first dose: at 0.5 hours post-dose on Day 1, on Days 2, 3, 7, and 15; and for the second dose: Days 15 (0.5 hours post-dose), 21, and 28)
- Serum Concentration of UTTR1147A at Specified Timepoints(For the first dose: at 0.5 hours post-dose on Day 1, on Days 2, 3, 7, and 15; and for the second dose: Days 15 (0.5 hours post-dose), 21, and 28)