A Study to Investigate Intravenous Tocilizumab in Participants With Moderate to Severe COVID-19 Pneumonia

COVID-19 Pneumonia Clinical Trial

— MARIPOSA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04363736
• Other study ID #: CA42481
• Status: Completed
• Phase: Phase 2
• Start date: May 5, 2020
• Est. completion date: August 12, 2020

Study information

• Verified date: August 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: August 12, 2020
• Est. primary completion date: August 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Pneumonia

Intervention

Drug:
• Tociliuzumab
Participants will receive IV TCZ.

Locations

Country	Name	City	State
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	University of Maryland	Baltimore	Maryland
United States	SUNY Downstate Medical Center.	Brooklyn	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	St. Jude Medical Center	Fullerton	California
United States	Houston Methodist Hospital	Houston	Texas
United States	Michael E. DeBakey VA Medical Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Jamaica Hospital Medical Center	Jamaica	New York
United States	LAC + USC Medical Center	Los Angeles	California
United States	USC Keck Medical Center of USC	Los Angeles	California
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic - Arizona	Phoenix	Arizona
United States	Allegheny Health Network (Pittsburg PA)	Pittsburgh	Pennsylvania
United States	Renown Institute for Heart & Vascular Health	Reno	Nevada
United States	Houston Methodist Sugar Land Hospital	Sugar Land	Texas
United States	Mercy St. Vincent Medical Center	Toledo	Ohio
United States	Medstar Georgetown University Hospital	Washington	District of Columbia
United States	St Joseph's Regional Medical Center	Wayne	New Jersey
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ		Baseline - Day 60
Primary	Serum Concentration of Ferritin Following Administration of IV TCZ		Baseline - Day 60
Primary	Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ		Baseline - Day 60
Primary	Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ		Baseline - Day 60
Secondary	Pecentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Up to Day 60
Secondary	Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time		Baseline - Day 60
Secondary	Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity	Time to Real-Time Polymerase Chain Reaction (RT-PCR) virus negativity was defined as the number of days from the first dose of study drug to when a negative RT-PCR SARS-CoV-2 assessment result was observed. Results are presented as a cumulative incidence function (CIF) with death as a competing risk.	Up to Day 28
Secondary	Proportion of Participants With Any Post-Treatment Infection		Up to Day 60