A Study to Investigate Intravenous Tocilizumab in Participants With Moderate to Severe COVID-19 Pneumonia
MARIPOSA
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
1 other identifier
interventional
97
1 country
24
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2020
Shorter than P25 for phase_2
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 21, 2020
CompletedFirst Posted
Study publicly available on registry
April 27, 2020
CompletedStudy Start
First participant enrolled
May 5, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 12, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
August 12, 2020
CompletedResults Posted
Study results publicly available
August 30, 2021
CompletedAugust 31, 2022
August 1, 2022
3 months
April 21, 2020
July 30, 2021
August 26, 2022
Conditions
Outcome Measures
Primary Outcomes (8)
Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab)
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.
Maximum Serum Concentration (Cmax) of Tocilizumab
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.
Clearance (CL) of Tocilizumab
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.
Volume of the Central Compartment (Vc) of Tocilizumab
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.
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Baseline - Day 60
Serum Concentration of Ferritin Following Administration of IV TCZ
Baseline - Day 60
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Baseline - Day 60
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Baseline - Day 60
Secondary Outcomes (4)
Pecentage of Participants With Adverse Events
Up to Day 60
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Baseline - Day 60
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
Up to Day 28
Proportion of Participants With Any Post-Treatment Infection
Up to Day 60
Study Arms (2)
TCZ 8 mg/kg
ACTIVE COMPARATORParticipants will receive intravenous (IV) tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
TCZ 4 mg/kg
EXPERIMENTALParticipants will receive IV tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
Interventions
Eligibility Criteria
You may qualify if:
- 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 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
Mayo Clinic - Arizona
Phoenix, Arizona, 85054, United States
St. Jude Medical Center
Fullerton, California, 92835, United States
LAC + USC Medical Center
Los Angeles, California, 90033, United States
USC Keck Medical Center of USC
Los Angeles, California, 90033, United States
Norwalk Hospital
Norwalk, Connecticut, 06856, United States
Medstar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Mayo Clinic
Jacksonville, Florida, 32224, United States
Advocate Christ Medical Center
Oak Lawn, Illinois, 60453, United States
Advocate Lutheran General Hospital
Park Ridge, Illinois, 60068, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Renown Institute for Heart & Vascular Health
Reno, Nevada, 89502, United States
St Joseph's Regional Medical Center
Wayne, New Jersey, 07470, United States
SUNY Downstate Medical Center.
Brooklyn, New York, 11203, United States
Jamaica Hospital Medical Center
Jamaica, New York, 11418, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Mercy St. Vincent Medical Center
Toledo, Ohio, 43608, United States
Lehigh Valley Health Network
Allentown, Pennsylvania, 18103, United States
Temple University Hospital
Philadelphia, Pennsylvania, 19140, United States
Allegheny Health Network (Pittsburg PA)
Pittsburgh, Pennsylvania, 15212, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
Michael E. DeBakey VA Medical Center
Houston, Texas, 77030, United States
Houston Methodist Sugar Land Hospital
Sugar Land, Texas, 77479, United States
Related Publications (2)
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.
PMID: 35024375DERIVEDTom 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.
PMID: 34612846DERIVED
MeSH Terms
Interventions
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 21, 2020
First Posted
April 27, 2020
Study Start
May 5, 2020
Primary Completion
August 12, 2020
Study Completion
August 12, 2020
Last Updated
August 31, 2022
Results First Posted
August 30, 2021
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).