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

Primary Purpose

COVID-19 Pneumonia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tociliuzumab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 Pneumonia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic - Arizona
  • St. Jude Medical Center
  • LAC + USC Medical Center
  • USC Keck Medical Center of USC
  • Norwalk Hospital
  • Medstar Georgetown University Hospital
  • Mayo Clinic
  • Advocate Christ Medical Center
  • Advocate Lutheran General Hospital
  • University of Maryland
  • Renown Institute for Heart & Vascular Health
  • St Joseph's Regional Medical Center
  • SUNY Downstate Medical Center.
  • Jamaica Hospital Medical Center
  • Wake Forest University Health Sciences
  • University Hospitals Cleveland Medical Center
  • Mercy St. Vincent Medical Center
  • Lehigh Valley Health Network
  • Temple University Hospital
  • Allegheny Health Network (Pittsburg PA)
  • Medical University of South Carolina
  • Houston Methodist Hospital
  • Michael E. DeBakey VA Medical Center
  • Houston Methodist Sugar Land Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

TCZ 8 mg/kg

TCZ 4 mg/kg

Arm Description

Participants will receive intravenous (IV) tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.

Participants will receive IV tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.

Outcomes

Primary Outcome Measures

Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab)
Maximum Serum Concentration (Cmax) of Tocilizumab
Clearance (CL) of Tocilizumab
Volume of the Central Compartment (Vc) of Tocilizumab
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Serum Concentration of Ferritin Following Administration of IV TCZ
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ

Secondary Outcome Measures

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.
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
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.
Proportion of Participants With Any Post-Treatment Infection

Full Information

First Posted
April 21, 2020
Last Updated
August 26, 2022
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT04363736
Brief Title
A Study to Investigate Intravenous Tocilizumab in Participants With Moderate to Severe COVID-19 Pneumonia
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
May 5, 2020 (Actual)
Primary Completion Date
August 12, 2020 (Actual)
Study Completion Date
August 12, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Pneumonia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TCZ 8 mg/kg
Arm Type
Active Comparator
Arm Description
Participants will receive intravenous (IV) tocilizumab (TCZ) at a dose of 8 mg/kg in addition to standard-of-care treatment.
Arm Title
TCZ 4 mg/kg
Arm Type
Experimental
Arm Description
Participants will receive IV tocilizumab (TCZ) at a dose of 4 mg/kg in addition to standard-of-care treatment.
Intervention Type
Drug
Intervention Name(s)
Tociliuzumab
Intervention Description
Participants will receive IV TCZ.
Primary Outcome Measure Information:
Title
Area Under the Curve From Day 0-28 (AUC0-d28) of Tocilizumab)
Time Frame
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.
Title
Maximum Serum Concentration (Cmax) of Tocilizumab
Time Frame
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.
Title
Clearance (CL) of Tocilizumab
Time Frame
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.
Title
Volume of the Central Compartment (Vc) of Tocilizumab
Time Frame
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.
Title
Serum Concentration of C-reactive Protein (CRP) Following Administration of IV TCZ
Time Frame
Baseline - Day 60
Title
Serum Concentration of Ferritin Following Administration of IV TCZ
Time Frame
Baseline - Day 60
Title
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of IV TCZ
Time Frame
Baseline - Day 60
Title
Serum Concentration of Interleukin-6 (IL-6) Following Administration of IV TCZ
Time Frame
Baseline - Day 60
Secondary Outcome Measure Information:
Title
Pecentage of Participants With Adverse Events
Description
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.
Time Frame
Up to Day 60
Title
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time
Time Frame
Baseline - Day 60
Title
Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity
Description
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.
Time Frame
Up to Day 28
Title
Proportion of Participants With Any Post-Treatment Infection
Time Frame
Up to Day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic - Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
St. Jude Medical Center
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
LAC + USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC Keck Medical Center of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Norwalk Hospital
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06856
Country
United States
Facility Name
Medstar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Advocate Christ Medical Center
City
Oak Lawn
State/Province
Illinois
ZIP/Postal Code
60453
Country
United States
Facility Name
Advocate Lutheran General Hospital
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Renown Institute for Heart & Vascular Health
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
St Joseph's Regional Medical Center
City
Wayne
State/Province
New Jersey
ZIP/Postal Code
07470
Country
United States
Facility Name
SUNY Downstate Medical Center.
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Jamaica Hospital Medical Center
City
Jamaica
State/Province
New York
ZIP/Postal Code
11418
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Mercy St. Vincent Medical Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43608
Country
United States
Facility Name
Lehigh Valley Health Network
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Allegheny Health Network (Pittsburg PA)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Michael E. DeBakey VA Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Houston Methodist Sugar Land Hospital
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77479
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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).
Citations:
PubMed Identifier
35024375
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.
Results Reference
derived
PubMed Identifier
34612846
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.
Results Reference
derived

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

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