Clinical trial NCT04363736: A Study to Investigate Intravenous Tocilizumab in Participants With Moderate to Severe COVID-19 Pneumonia
Official title: A Phase-II, Open-Label, Randomized, Multicenter Study to Investigate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of 8 mg/kg or 4mg/kg Intravenous Tocilizumab in Patients With Moderate to Severe COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19 Pneumonia
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-04-27
Enrollment: 97
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 study will assess the pharmacodynamics, pharmacokinetics, safety and efficacy of two different doses of tocilizumab (TCZ) in combination with standard-of-care (SOC) in hospitalized adult participants with moderate to severe COVID-19 pneumonia.


Eligibility criteria: Inclusion Criteria

* Hospitalization with COVID-19 pneumonia confirmed by a positive polymerase chain reaction (PCR) of any specimen \[e.g., respiratory, blood, urine, stool, and other bodily fluids\]) and evidence of pneumonia on chest X-ray or computed tomography scan
* For severe patients, SpO2 \</= 93% or PaO2/FiO2 \< 300 mmHg. If a participant is on supplemental oxygen with SpO2 \> 93%, but desaturation \</= to 93% on lower supplemental oxygen or ambient air is documented during screening, the inclusion criterion is met
* For moderate patients (those who do not qualify as severe based oxygen requirements), CRP \> 2 x upper limit of normal (ULN) is required
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined by the protocol
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined by the protocol

Exclusion Criteria

* Known severe allergic reactions to TCZ or other monoclonal antibodies
* Active tuberculosis (TB) infection
* Suspected active bacterial, fungal, viral, or other infection (besides SARS-CoV-2)
* Participants who are on a mechanical ventilator \> 24 hours or extracorporeal membrane oxygenation (ECMO), in shock, or combination thereof with other organ failure requiring treatment in an ICU
* In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
* Receipt of oral anti-rejection or immunomodulatory drugs (including TCZ) within the past 3 months
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 10 x ULN detected within 24 hours at screening or at baseline (according to local laboratory reference ranges)
* Absolute neutrophil count (ANC) \< 1000/uL at screening and baseline (according to local laboratory reference ranges)
* Platelet count \< 50,000/uL at screening and baseline (according to local laboratory reference ranges)
* Pregnancy or breastfeeding, or positive pregnancy test at a predose examination
* Treatment with an investigational drug within 5 drug-elimination half-lives or 30 days (whichever is longer) of randomization

Primary outcomes:
measure: Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab)
timeFrame: Days 0-28. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.
measure: Maximum Serum Concentration (Cmax) of Tocilizumab
timeFrame: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.
measure: Clearance (CL) of Tocilizumab
timeFrame: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.
measure: Volume of the Central Compartment (Vc) of Tocilizumab
timeFrame: Baseline - Day 60. Participants received a second dose within 8-24 hours after the initial infusion of TCZ at the discretion of the investigator upon clinically significant demonstration of worsening signs or symptoms.
measure: Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
timeFrame: Baseline - Day 60
measure: Serum Concentration of Ferritin Following Administration of IV TCZ
timeFrame: Baseline - Day 60
measure: Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
timeFrame: Baseline - Day 60
measure: Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
timeFrame: Baseline - Day 60
Secondary outcomes:
measure: Pecentage of Participants With Adverse Events
timeFrame: Up to Day 60
measure: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
timeFrame: Baseline - Day 60
measure: Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
timeFrame: Up to Day 28
measure: Proportion of Participants With Any Post-Treatment Infection
timeFrame: Up to Day 60
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Fullerton
country: United States
facility: St. Jude Medical Center
state: California
city: Los Angeles
country: United States
facility: LAC + USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC Keck Medical Center of USC
state: California
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Washington
country: United States
facility: Medstar Georgetown University Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Reno
country: United States
facility: Renown Institute for Heart & Vascular Health
state: Nevada
city: Wayne
country: United States
facility: St Joseph's Regional Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center.
state: New York
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Toledo
country: United States
facility: Mercy St. Vincent Medical Center
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network (Pittsburg PA)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center
state: Texas
city: Sugar Land
country: United States
facility: Houston Methodist Sugar Land Hospital
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kumar PN, Hernandez-Sanchez J, Nagel S, Feng Y, Cai F, Rabin J, Morse CG, Nadig NR, Ashraf O, Gotur DB, McComsey GA, Gafoor K, Perin P, Thornton SC, Stubbings W, Lin CJF, Tsai L. Safety and Efficacy of Tocilizumab 4 or 8 mg/kg in Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial. Open Forum Infect Dis. 2021 Dec 4;9(1):ofab608. doi: 10.1093/ofid/ofab608. eCollection 2022 Jan.
citation: Tom J, Bao M, Tsai L, Qamra A, Summers D, Carrasco-Triguero M, McBride J, Rosenberger CM, Lin CJF, Stubbings W, Blyth KG, Carratala J, Francois B, Benfield T, Haslem D, Bonfanti P, van der Leest CH, Rohatgi N, Wiese L, Luyt CE, Kheradmand F, Rosas IO, Cai F. Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial. Crit Care Med. 2022 Mar 1;50(3):398-409. doi: 10.1097/CCM.0000000000005229.