Critical Confirmed Coronavirus Disease (COVID)-19Phase 2NCT04380961
A Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical Confirmed Coronavirus Disease (COVID)-19
A Phase 2 study testing Sirukumab in people with Critical Confirmed Coronavirus Disease (COVID)-19, run by Janssen Pharmaceutica N.V., Belgium at 16 sites in United States.
Trial summary
The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19. Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- Critical Confirmed Coronavirus Disease (COVID)-19
- What is being tested?
- Sirukumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 212 participants
- Where
- 16 sitesUnited States
- Study dates
- 24 Apr 2020to 24 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hospitalized
- Has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by real time-polymerase chain reaction (PCR) at any time before randomization
- Evidence of infiltrates by chest X-ray, chest computed tomography (CT), lung ultrasound, or chest auscultation (rales, crackles)
- Informed consent must be obtained from the participant indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
- Critical COVID-19 disease, defined as: Requires supplemental oxygen delivered by nonrebreather mask or high-flow nasal cannula or use of non-invasive or invasive ventilation or requiring treatment in an intensive care unit
- AND corresponding to category 4 on the 6-point ordinal recovery scale, that is: requires one of the above modalities to sustain a peripheral capillary oxygen saturation (SpO2) greater than (>) 93 percent (%) with a fraction of inspired oxygen (FiO2) of 50% or higher. Note, the use of other devices may fit with category 4 if the FiO2 is 50% or higher.
- OR, corresponding to category 5 on the 6-point ordinal recovery scale, that is partial pressure of oxygen in arterial per percentage of inspired oxygen (PaO2/FiO2) ratio < 300 millimeter of mercury (mmHg) while on invasive mechanical ventilation or veno-venous extracorporeal membrane oxygenation (ECMO) for less than 48 hours prior to screening
Who cannot join
- On invasive mechanical ventilation or on veno-venous ECMO for >48 hours at time of screening
- Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned dose of study intervention. Note: the investigator must ensure that the participant is not enrolled in another COVID-19 study with an investigational intervention (apart from the exception specified below) prior to completion of Day 28 of the current study. Exception: participation in a single arm study, a non-blinded controlled study, expanded access, compassionate use program or any other program that is not a blinded study is allowed if it is conducted with one of the following: agents with demonstrated in vitro-effect against SARSCoV- 2, as mentioned in the center of disease control and prevention (CDC) guidelines and convalescent plasma
- Current confirmed or high suspicion for pulmonary embolus, hemodynamic significant pericardial effusion, myocarditis, or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification AND/OR Current evidence of active cardiac ischemia
- Has a history of respiratory condition (that is, asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, fibrotic lung disease) that requires home oxygen supplementation, supportive non-invasive ventilation or, is status/post lung volume reduction surgery (LVRS). Exception: Participants with sleep apnea using supportive non-invasive ventilation (continuous positive airway pressure [CPAP]) at screening may be included
- On renal replacement therapy (defined as peritoneal dialysis or hemodialysis)
- Screening laboratory test result as follows: absolute neutrophil count (ANC) <1.0*10^3 cells/microliter; Platelet count <50*10^3 cells/microliter; estimated glomerular filtration rate (eGFR) <=30 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2); Bilirubin >2* upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin; alanine aminotransferase/ aspartate aminotransferase (ALT) >5*ULN; Prothrombin time (PT)/international normalized ratio (INR) >1.5*ULN or activated partial thromboplastin time (aPTT) >1.5*ULN related to known coagulopathy or bleeding disorder (the participant can receive anticoagulant therapies for underlying conditions, or as systematic thromboprophylaxis due to COVID-19, or as part of the treatment of complications of COVID-19, but cannot participate in a clinical study with anticoagulants for COVID-19)
Show all 11Show fewer
- Pregnant or breastfeeding, unless in the opinion of the investigator, the benefit outweighs the risks
- Has active hepatitis B or C infection or has human immunodeficiency virus infection or acquired immune deficiency syndrome (HIV/AIDS) based on medical history and/or concomitant medication
- Known active or latent tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB based on medical history and/or concomitant medication
- Evidence of active bacterial (including but not limited to bacterial pneumonia), fungal, viral or opportunistic infection (other than SARS-CoV-2)
- Currently active clinically significant (example, causing hemodynamic instability and/or causing hypoxemia) and uncontrolled arrhythmia
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Mercury Street Medical Group, PLLC
Butte, Montana, 59701
Great Lakes Clinical Trials
Chicago, Illinois, 60640
Baylor Scott & White Research Institute
Dallas, Texas, 75246
Henry Ford Hospital
Detroit, Michigan, 48202
Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center
Fort Lauderdale, Florida, 33308
Baylor All Saints Medical Center at Fort Worth
Fort Worth, Texas, 76104
East Carolina University
Greenville, North Carolina, 27834
MemorialCare Research Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Loyola University Medical Center
Maywood, Illinois, 60153
Louisiana State University Health Sciences Center
New Orleans, Louisiana, 70012
Saint Michaels Medical Center - Infectious Disease
Newark, New Jersey, 07102
Hoag Memorial Hospital
Newport Beach, California, 92663
University of Illinois College of Medicine at Peoria
Peoria, Illinois, 61637
Beaumont Health Systems
Royal Oak, Michigan, 48073
Washington University School of Medicine
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
Official title: Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical COVID-19 Disease
The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.
Read the detailed description
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped, positive-sense, single-stranded ribonucleic acid (RNA) betacoronavirus. Symptoms of COVID-19 infection may appear from 2 to 14 days following exposure, with the spectrum of illnesses ranging from mild symptoms to severe illness or death. The identification of SARS-CoV-2 follows the emergence of 2 other novel betacoronaviruses: SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. While an understanding of the epidemiology and clinical spectrum of COVID-19 is still evolving during the ongoing pandemic, the current knowledge of the disease burden highlights the urgent medical need to develop a treatment. Sirukumab (also known as CNTO136) is a human anti-interleukin (IL)-6 immunoglobulin G1 kappa (IgG1k) monoclonal antibody (mAb). Sirukumab binds with high affinity and specificity to human IL-6 and as a result inhibits IL-6-mediated signaling and the biological effects of IL-6. The study will include a Screening Phase (up to 1 Day), a Treatment Phase (Day 1 to Day 28) and a Follow-up Phase (post Day 28, follow-up phone calls on Week 8, Week 12 and Week 16). Safety evaluations will include monitoring of adverse events and serious adverse events, physical examinations, vital sign measurements, electrocardiograms, clinical laboratory tests, pregnancy testing, and checking of vital status. The entire study duration for each participant will be 16 weeks.
- Being tested
- Sirukumab, Placebo, Standard of Care (SOC)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirukumabDrug
Also called CNTO136
Participants will receive single dose infusion of sirukumab on Day 1.
PlaceboDrug
Participants will receive placebo IV single dose infusion on Day 1.
Standard of Care (SOC)Other
SOC treatment will be determined by the investigator based on local practice and consists of supportive care.
| Study group | Role | What they receive |
|---|---|---|
| Sirukumab | Experimental | Participants will receive single intravenously (IV) dose infusion of sirukumab on Day 1 along with standard of care treatment. Receives: Drug: Sirukumab; Other: Standard of Care (SOC) |
| Placebo | Placebo comparator | Participants will receive IV single dose infusion of placebo on Day 1 along with standard of care treatment. Receives: Drug: Placebo; Other: Standard of Care (SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal Clinical Recovery Scale (CRS): Primary Analysis Set
Time to sustained improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: Up to Day 28
Secondary outcomes (27)
Percentage of Participants With an Improvement of At Least 2 Categories Compared to Baseline on 6-point Ordinal CRS
Percentage of participants with an improvement of at least 2 Categories compared to baseline on 6-point ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: Day 28
Percentage of Participants With All-cause Mortality Up to 28 Days
Percentage of participants with all-cause mortality up to 28 days were reported. All-cause mortality included all deaths of participants due to any cause.
Measured: Up to 28 days
Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal CRS: Intent-to-Treat (ITT) Set
Time to sustained improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: Up to Day 28
Percentage of Participants With an Improvement of at Least 2 Categories Compared to Baseline on 6-point Ordinal CRS: ITT Set
Percentage of participants with an improvement of at least 2 categories compared to baseline on 6-point ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: Day 28
Percentage of Participants With All-cause Mortality: ITT Set
Percentage of participants with all-cause mortality were reported. All-cause mortality included all deaths of participants due to any cause.
Measured: Day 28
Percentage of Participants With Serious Adverse Events (SAEs) (Treatment Phase)
Percentage of participants with SAEs were reported. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Measured: Up to Day 28
Percentage of Participants With Related Adverse Events (AEs)
Percentage of participants with related AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Measured: Up to Day 28
Percentage of Participants With Severe or Life-threatening, Bacterial, Invasive Fungal, Viral or Opportunistic Infections
Percentage of participants with severe or Life-threatening, bacterial, invasive fungal, viral or opportunistic infections were reported.
Measured: Up to Day 28
Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia
Percentage of participants with Grade 3 and 4 neutropenia and lymphocytopenia were reported. The laboratory abnormalities were determined as per division of microbiology and infectious diseases (DMID) adult toxicity as Grade 1: mild (transient or mild discomfort [less than {<} 48 hours]; no medical intervention/therapy required); Grade 2: moderate (mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required); Grade 3: severe (severe marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible); Grade 4: life-threatening (extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable).
Measured: Up to Day 28
Percentage of Participants With Increased Alanine Transaminase (ALT) Greater Than or Equal to (>=)3*Upper Limit Normal (ULN) Combined With Increased Bilirubin Greater Than (>)2*ULN
Percentage of participants with increased ALT >=3*ULN combined with increased bilirubin >2*ULN were reported.
Measured: Up to Day 28
Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: Primary Analysis Set
Time to sustained improvement is defined as an improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: Up to Day 28
Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set
Time to sustained improvement is defined as an improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale, sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: Up to Day 28
Percentage of Participants With an Improvement of at Least 1 Category Compared to Baseline on 6-point Ordinal CRS: Primary Analysis Set
The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6), reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: (category 1) not hospitalized, including participants on low level of oxygen; Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: Day 28
Percentage of Participants With an Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set
The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening
Measured: Day 28
Time From Study Intervention Administration to End of Oxygen Supplementation
Time from study intervention administration to end of oxygen supplementation was reported.
Measured: Up to Day 28
Time From Study Intervention Administration to Hospital Discharge Among the Surviving Participants
Time from study intervention administration to hospital discharge among the surviving participants was reported.
Measured: Up to Day 28
Total Length of Hospitalization Among the Surviving Participants
Total length of hospitalization, defined as total duration of hospital stay, among the surviving participants was reported.
Measured: Up to Day 28
Number of Ventilation Free Days
Number of ventilation free days in participants on invasive mechanical ventilation (IVM)/extracorporeal membrane oxygenation (ECMO) at baseline was reported.
Measured: Up to Day 28
Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set
Percentage of participants with clinical status as assessed by 6-point Ordinal CRS were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: Not hospitalized, not requiring supplemental oxygen (category 1.1); Not hospitalized, requiring supplemental oxygen (category 1.2); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: On Day 7, 14, 21, 28
Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set
Percentage of participants with clinical status as assessed by 6-point Ordinal CRS (ITT Set) were reported. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: Not hospitalized, not requiring supplemental oxygen (category 1.1); Not hospitalized, requiring supplemental oxygen (category 1.2); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: On Days 7, 14, 21, 28
Total Time on Invasive Mechanical Ventilation
Total time on invasive mechanical ventilation in participants who were on invasive mechanical ventilation at baseline was reported.
Measured: Up to Day 28
Percentage of Participants With a Worse Category Relative to Baseline on the 6-point Ordinal CRS
Percentage of participants with a worse category relative to baseline on the 6-point ordinal CRS for at least one of the daily assessment during the reporting period Day 5 and Day 28 were reported. he 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
Measured: From Day 5 up to Day 28
Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time
Percentage of participants with ECMO over time were reported.
Measured: From Day 1 up to Day 28
Total Time on ECMO
Total time for participants on ECMO was reported.
Measured: Up to Day 28
Percentage of Alive Participants at Day 28, Week 8, and Week 16
Percentage of alive participants at Day 28, Week 8, and Week 16 were reported. For this outcome measure, at Week 8, data was not collected for participants due to pandemic situation.
Measured: On Day 28, Week 8 and Week 16
Percentage of Alive Participants That Required Readmission at Week 8, and Week 16
Percentage of alive participants that required readmission at Week 8, and Week 16 were reported. For this outcome measure, at Week 8 and Week 16, data was not collected for participants due to pandemic situation.
Measured: Week 8 and Week 16
Percentage of Participants With SAEs (Follow-up Phase)
Percentage of participants with SAEs were reported. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Measured: From Week 4 up to Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2020
- Study start24 Apr 2020
- Primary completion9 Apr 2021
- Study completion24 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Critical Confirmed Coronavirus Disease (COVID)-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 212 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Pharmaceutica N.V., Belgium
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Pharmaceutica N.V., Belgium Clinical Trial, Study director, Janssen Pharmaceutica N.V., Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04380961
- Sponsor's protocol ID
- CR108820
- Other IDs
- CNTO136COV2001, 2020-003056-32
- Status last verified
- May 2022
- First submitted
- 7 May 2020
- Last updated
- 21 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Publications
Thys K, Loza MJ, Lynn L, Callewaert K, Varma L, Crabbe M, Van Wesenbeeck L, Van Landuyt E, De Meyer S, Aerssens J, Verbrugge I. Pharmacodynamic, prognostic, and predictive biomarkers in severe and critical COVID-19 patients treated with sirukumab. Sci Rep. 2024 Oct 3;14(1):22981. doi: 10.1038/s41598-024-74196-9.
PubMed 39362933
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical COVID-19 Disease
- ClinicalTrials.gov ID
- NCT04380961
- Acronym / sponsor ID
- CR108820
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 212 participants (actual)
- Lead sponsor
- Janssen Pharmaceutica N.V., BelgiumIndustry (pharma, biotech, devices)
- Study start
- 24 Apr 2020 (actual)
- Primary completion
- 9 Apr 2021 (actual)
- Study completion
- 24 Jun 2021 (actual)
- First posted
- 8 May 2020 (actual)
- Results
- Posted 21 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.
Detailed description
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped, positive-sense, single-stranded ribonucleic acid (RNA) betacoronavirus. Symptoms of COVID-19 infection may appear from 2 to 14 days following exposure, with the spectrum of illnesses ranging from mild symptoms to severe illness or death. The identification of SARS-CoV-2 follows the emergence of 2 other novel betacoronaviruses: SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. While an understanding of the epidemiology and clinical spectrum of COVID-19 is still evolving during the ongoing pandemic, the current knowledge of the disease burden highlights the urgent medical need to develop a treatment. Sirukumab (also known as CNTO136) is a human anti-interleukin (IL)-6 immunoglobulin G1 kappa (IgG1k) monoclonal antibody (mAb). Sirukumab binds with high affinity and specificity to human IL-6 and as a result inhibits IL-6-mediated signaling and the biological effects of IL-6. The study will include a Screening Phase (up to 1 Day), a Treatment Phase (Day 1 to Day 28) and a Follow-up Phase (post Day 28, follow-up phone calls on Week 8, Week 12 and Week 16). Safety evaluations will include monitoring of adverse events and serious adverse events, physical examinations, vital sign measurements, electrocardiograms, clinical laboratory tests, pregnancy testing, and checking of vital status. The entire study duration for each participant will be 16 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirukumab | Experimental | Drug: Sirukumab, Other: Standard of Care (SOC)Participants will receive single intravenously (IV) dose infusion of sirukumab on Day 1 along with standard of care treatment. |
| Placebo | Placebo comparator | Drug: Placebo, Other: Standard of Care (SOC)Participants will receive IV single dose infusion of placebo on Day 1 along with standard of care treatment. |
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Hospitalized
- Has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by real time-polymerase chain reaction (PCR) at any time before randomization
- Evidence of infiltrates by chest X-ray, chest computed tomography (CT), lung ultrasound, or chest auscultation (rales, crackles)
- Informed consent must be obtained from the participant indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
- Critical COVID-19 disease, defined as: Requires supplemental oxygen delivered by nonrebreather mask or high-flow nasal cannula or use of non-invasive or invasive ventilation or requiring treatment in an intensive care unit
Key exclusion criteria (11 listed)
- On invasive mechanical ventilation or on veno-venous ECMO for >48 hours at time of screening
- Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned dose of study intervention. Note: the investigator must ensure that the participant is not enrolled in another COVID-19 study with an investigational intervention (apart from the exception specified below) prior to completion of Day 28 of the current study. Exception: participation in a single arm study, a non-blinded controlled study, expanded access, compassionate use program or any other program that is not a blinded study is allowed if it is conducted with one of the following: agents with demonstrated in vitro-effect against SARSCoV- 2, as mentioned in the center of disease control and prevention (CDC) guidelines and convalescent plasma
- Current confirmed or high suspicion for pulmonary embolus, hemodynamic significant pericardial effusion, myocarditis, or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification AND/OR Current evidence of active cardiac ischemia
- Has a history of respiratory condition (that is, asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, fibrotic lung disease) that requires home oxygen supplementation, supportive non-invasive ventilation or, is status/post lung volume reduction surgery (LVRS). Exception: Participants with sleep apnea using supportive non-invasive ventilation (continuous positive airway pressure [CPAP]) at screening may be included
- On renal replacement therapy (defined as peritoneal dialysis or hemodialysis)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirukumabAlso: CNTO136Participants will receive single dose infusion of sirukumab on Day 1. | Drug | Sirukumab |
| PlaceboParticipants will receive placebo IV single dose infusion on Day 1. | Drug | Placebo |
| Standard of Care (SOC)SOC treatment will be determined by the investigator based on local practice and consists of supportive care. | Other | Placebo, Sirukumab |
Primary outcome
Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal Clinical Recovery Scale (CRS): Primary Analysis Set
Time frame: Up to Day 28
Time to sustained improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
27 secondary outcomes
Percentage of Participants With an Improvement of At Least 2 Categories Compared to Baseline on 6-point Ordinal CRS
Time frame: Day 28
Percentage of Participants With All-cause Mortality Up to 28 Days
Time frame: Up to 28 days
Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal CRS: Intent-to-Treat (ITT) Set
Time frame: Up to Day 28
Percentage of Participants With an Improvement of at Least 2 Categories Compared to Baseline on 6-point Ordinal CRS: ITT Set
Time frame: Day 28
Percentage of Participants With All-cause Mortality: ITT Set
Time frame: Day 28
Percentage of Participants With Serious Adverse Events (SAEs) (Treatment Phase)
Time frame: Up to Day 28
Percentage of Participants With Related Adverse Events (AEs)
Time frame: Up to Day 28
Percentage of Participants With Severe or Life-threatening, Bacterial, Invasive Fungal, Viral or Opportunistic Infections
Time frame: Up to Day 28
Percentage of Participants With Grade 3 and 4 Neutropenia and Lymphocytopenia
Time frame: Up to Day 28
Percentage of Participants With Increased Alanine Transaminase (ALT) Greater Than or Equal to (>=)3*Upper Limit Normal (ULN) Combined With Increased Bilirubin Greater Than (>)2*ULN
Time frame: Up to Day 28
Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: Primary Analysis Set
Time frame: Up to Day 28
Time to Sustained Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set
Time frame: Up to Day 28
Percentage of Participants With an Improvement of at Least 1 Category Compared to Baseline on 6-point Ordinal CRS: Primary Analysis Set
Time frame: Day 28
Percentage of Participants With an Improvement of at Least 1 Category on 6-point Ordinal CRS: ITT Set
Time frame: Day 28
Time From Study Intervention Administration to End of Oxygen Supplementation
Time frame: Up to Day 28
Time From Study Intervention Administration to Hospital Discharge Among the Surviving Participants
Time frame: Up to Day 28
Total Length of Hospitalization Among the Surviving Participants
Time frame: Up to Day 28
Number of Ventilation Free Days
Time frame: Up to Day 28
Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: Primary Analysis Set
Time frame: On Day 7, 14, 21, 28
Percentage of Participants With Clinical Status as Assessed by 6-point Ordinal CRS: ITT Set
Time frame: On Days 7, 14, 21, 28
Total Time on Invasive Mechanical Ventilation
Time frame: Up to Day 28
Percentage of Participants With a Worse Category Relative to Baseline on the 6-point Ordinal CRS
Time frame: From Day 5 up to Day 28
Percentage of Participants With Extracorporeal Membrane Oxygenation (ECMO) Over Time
Time frame: From Day 1 up to Day 28
Total Time on ECMO
Time frame: Up to Day 28
Percentage of Alive Participants at Day 28, Week 8, and Week 16
Time frame: On Day 28, Week 8 and Week 16
Percentage of Alive Participants That Required Readmission at Week 8, and Week 16
Time frame: Week 8 and Week 16
Percentage of Participants With SAEs (Follow-up Phase)
Time frame: From Week 4 up to Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39362933Thys K, Loza MJ, Lynn L, Callewaert K, Varma L, Crabbe M, Van Wesenbeeck L, Van Landuyt E, De Meyer S, Aerssens J, Verbrugge I. Pharmacodynamic, prognostic, and predictive biomarkers in severe and critical COVID-19 patients treated with sirukumab. Sci Rep. 2024 Oct 3;14(1):22981. doi: 10.1038/s41598-024-74196-9.
- Individual participant dataSharing planned: Yes. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Pharmaceutica N.V., Belgium Clinical Trial study director
Janssen Pharmaceutica N.V., Belgium
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirukumab in people with Critical Confirmed Coronavirus Disease (COVID)-19, run by Janssen Pharmaceutica N.V., Belgium at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Sustained Improvement of at Least 2 Categories on 6-point Ordinal Clinical Recovery Scale (CRS): Primary Analysis Set (time frame: Up to Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04380961, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2022.