Clinical trial NCT04386616: A Study to Evaluate the Safety and Efficacy of MSTT1041A (Astegolimab) or UTTR1147A in Patients With Severe COVID-19 Pneumonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19 Pneumonia
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2020-05-13
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* History of cancer within the previous 5 years unless it has been adequately treated and considered cured or remission-free in the investigator's judgment
* Clinical evidence of active or unstable cardiovascular disease (e.g., acute myocardial ischemia or decompensated heart failure), as determined by investigator assessment, ECG, laboratory assessment, or echocardiographic data
* History of moderate or severe allergic, anaphylactic, or anaphylactoid reactions or hypersensitivity to any component of study treatment

Primary outcomes:
measure: 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
timeFrame: From Baseline up to 28 days
Secondary outcomes:
measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status by Day 28
timeFrame: From Baseline up to 28 days
measure: Time to Hospital Discharge or "Ready for Discharge" by Day 28
timeFrame: Up to 28 days
measure: Duration of Supplemental Oxygen by Day 28
timeFrame: Up to 28 days
measure: Percentage of Participants Alive and Free of Respiratory Failure by Day 28
timeFrame: Up to 28 days
measure: Clinical Status Score at Day 14, Assessed Using a 7-Category Ordinal Scale
timeFrame: Day 14
measure: Clinical Status Score at Day 28, Assessed Using a 7-Category Ordinal Scale
timeFrame: Day 28
measure: Percentage of Participants Needing Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Day 28
timeFrame: Up to 28 days
measure: Number of Ventilator-Free Days by Day 28
timeFrame: Up to 28 days
measure: Percentage of Participants With an Intensive Care Unit (ICU) Stay by Day 28
timeFrame: Up to 28 days
measure: Duration of Intensive Care Unit (ICU) Stay by Day 28
timeFrame: Up to 28 days
measure: Time to Clinical Failure by Day 28, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First)
timeFrame: Up to 28 days
measure: Percentage of Participants Who Died by Day 14
timeFrame: Up to Day 14
measure: Percentage of Participants Who Died by Day 28
timeFrame: Up to Day 28
measure: Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) Aggregate Score of ≤2 Maintained for 24 Hours
timeFrame: Up to 28 days
measure: 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)
timeFrame: From Baseline until study completion/discontinuation (up to 60 days)
measure: Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline
timeFrame: From Baseline up to 60 days
measure: Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline
timeFrame: From Baseline up to 60 days
measure: Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints
timeFrame: Baseline, Days 14 and 28, Discharge Day (up to Day 28), and Study Completion Visit (up to Day 60)
measure: Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline
timeFrame: At Baseline (pre-dose on Day 1) and post-baseline (Days 15 and 28; and discharge day and study completion [up to 60 days])
measure: Serum Concentration of UTTR1147A at Specified Timepoints
timeFrame: 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
measure: Serum Concentration of MSTT1041A at Specified Timepoints
timeFrame: 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
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas For Medical Sciences
state: Arkansas
city: Chula Vista
country: United States
facility: eStudySite - Chula Vista - PPDS
state: California
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Torrance
country: United States
facility: Torrance Memorial Medical Center
state: California
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Bay Pines
country: United States
facility: Bay Pines VA Medical Center - NAVREF
state: Florida
city: Marietta
country: United States
facility: WellStar Research Institute
state: Georgia
city: Alexandria
country: United States
facility: DM Clinical Research - Alexandria Cardiology Clinic - ERN - PPDS
state: Louisiana
city: Metairie
country: United States
facility: MedPharmics
state: Louisiana
city: New Orleans
country: United States
facility: Southeast Louisiana Veterans Health Care System - NAVREF
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Paterson
country: United States
facility: St. Joseph'S Regional Medical Center
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Lincoln Medical Mental Health Center
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital; Department of Pharmacy
state: New York
city: Toledo
country: United States
facility: Mercy St. Vincent Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center; Investigational Drug Services/Regional Research
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Dallas
country: United States
facility: Parkland Health & Hospital System
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation; Clinic/Outpatient Facility
state: Washington
city: Rio de Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas FIOCRUZ
state: RJ
city: Porto Alegre
country: Brazil
facility: Santa Casa de Porto Alegre
state: RS
city: Campinas
country: Brazil
facility: Hospital E Maternidade Celso Pierro PUCCAMP
state: SP
city: Sao Jose Do Rio Preto
country: Brazil
facility: Hospital de Base Da Faculdade de Medicina de Sao Jose Do Rio Preto
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Coração - HCFMUSP
state: SP
city: Guadalajara
country: Mexico
facility: Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca
state: Jalisco
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo LEON
city: Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
city: Mexico
country: Mexico
facility: Instituto Nacional De Enfermedades Respiratorias INER National Institute of Respiratory Diseases
city: Tijuana
country: Mexico
facility: Hospital General de Tijuana
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Marbella
country: Spain
facility: Hospital Costa del Sol; Servicio de Oncologia
state: Malaga
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Guadalajara
country: Spain
facility: Hospital General Universitario de Guadalajara
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - H. Clinico
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario Valladolid
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: