A study to evaluate the safety and efficacy of tocilizumab in patients with severe COVID-19 pneumonia
| ISRCTN | ISRCTN13593711 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13593711 |
| EudraCT/CTIS number | 2020-001154-22 |
| IRAS number | 282099 |
| ClinicalTrials.gov number | NCT04320615 |
| Secondary identifying numbers | WA42380, IRAS 282099 |
- Submission date
- 12/11/2020
- Registration date
- 21/01/2021
- Last edited
- 17/03/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of April 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.
The aim of this study is to assess the effectiveness and safety of tocilizumab in combination with standard of care compared with matching placebo (dummy drug) in combination with standard of care in hospitalized adult patients with severe COVID-19 pneumonia.
Who can participate?
Adult patients with severe COVID-19 pneumonia who meet the entry criteria
What does the study involve?
Patients will be randomly allocated to receive treatment with either tocilizumab or a matching placebo. Study treatment must be given in combination with standard of care. For both arms, if the clinical signs or symptoms worsen or do not improve, one additional infusion of blinded treatment of tocilizumab or placebo can be given, 8–24 hours after the initial infusion. The study assessments to be conducted include the following: physical examination, vital signs, oxygen saturation, assessment of consciousness, presence and absence of breathing support, adverse events, other treatments, clinical laboratory tests, and nasopharyngeal swabs.
What are the possible benefits and risks of participating?
At the time of the study design, there were no drugs licensed for the treatment of patients with COVID-19. Given the results of previous studies, tocilizumab along with standard of care could be effective at treating COVID-19 in hospitalized populations more effectively than the current standard of care alone. Extensive safety data have previously been generated on the use of tocilizumab in other indications. Therefore, a placebo-controlled study in combination with SOC to assess safety and efficacy of TCZ in hospitalized patients with severe COVID-19 pneumonia is justified to address the high unmet need and burden of disease in this severely ill population.
Where is the study run from?
Genentech (USA)
When is the study starting and how long is it expected to run for?
March 2020 to July 2020
Who is funding the study?
1. Genentech (USA)
2. Biomedical Advanced Research and Development Authority (USA)
Who is the main contact?
global-roche-genentech-trials@gene.com, reference study ID WA42380
Contact information
Public
1 DNA Way
South San Francisco
94080
United States of America
| Phone | +1 (0)888 662 6728 |
|---|---|
| global-roche-genentech-trials@gene.com |
Study information
| Study design | Randomized double-blind placebo-controlled multicenter study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | A randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety and efficacy of tocilizumab in patients with severe COVID-19 pneumonia |
| Study acronym | COVACTA |
| Study objectives | To evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia. |
| Ethics approval(s) | Approved 30/03/2020, Advarra (6940 Columbia Gateway Drive, Columbia, MD, 21046, USA; +1 4108842900; no email provided), ref: none provided |
| Health condition(s) or problem(s) studied | COVID-19 (SARS-CoV-2 infection) pneumonia |
| Intervention | Patients will be randomized as soon as possible after screening at a 2:1 ratio to receive blinded treatment of either TCZ or a matching placebo, respectively. Study treatment must be given in combination with standard of care (SOC). The randomization will be stratified by geographic region (North America and Europe) and mechanical ventilation (yes, no). The proportion of patients who are on a mechanical ventilator at the time of randomization will be capped at no more than 50% of the overall study population. Experimental arm: Participants will receive one intravenous (IV) infusion of tocilizumab (TCZ), dosed at 8 mg/kg, up to a maximum dose of 800 mg. Up to one additional dose may be given if clinical symptoms worsen or show no improvement within 8-24 hours after the initial dose. Placebo arm: Participants will receive one IV infusion of placebo matched to TCZ. Up to one additional dose may be given if clinical symptoms worsen or show no improvement within 8-24 hours after the initial dose. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Tocilizumab |
| Primary outcome measure | Clinical status assessed using a 7-category ordinal scale on day 28 |
| Secondary outcome measures | Measured using patient records (unless otherwise noted): 1. Time to clinical improvement (TTCI), defined as a National Early Warning Score 2 (NEWS2) of </= 2 maintained for 24 hours, up to 60 days 2. Time to improvement of at least two categories relative to baseline on a 7-category ordinal scale of clinical status, up to 60 days 3. Incidence of mechanical ventilation, up to 60 days 4. Ventilator-free days up to Day 28 5. Incidence of intensive care unit (ICU) stay up to 60 days 6. Duration of ICU stay up to 60 days 7. Time to clinical failure, from first dose to time of death, mechanical ventilation, ICU admission, or study withdrawal (whichever occurs first, for up to 60 days). If already in ICU on ventilation, failure = a one-category worsening on the ordinal scale, withdrawal, or death 8. Mortality rate on days 7, 14, 21, 28, and 60 9. Time to hospital discharge up to 60 days 10. Time to recovery, defined as discharged or “ready for discharge” (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or 2L supplemental oxygen); OR, in a non-ICU hospital ward (or “ready for hospital ward”) not requiring supplemental oxygen, up to 60 days 11. Duration of time on supplemental oxygen up to 60 days 12. Percentage of participants with adverse events up to 60 days 13. COVID-19 (SARS-CoV-2) viral load over time, up to 60 days measured using RT-PCR 14. Time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity, up to 60 days measured using RT-PCR 15. Proportion of participants with post-treatment infection, up to 60 days measured using AE summary 16. Serum concentration of IL-6, up to 60 days measured using ELISA 17. Serum concentration of sIL-6R, up to 60 days measured using ELISA 18. Serum concentration of Ferritin, up to 60 days measured using ELISA 19. Serum concentration of C-reactive protein (CRP), up to 60 days measured using ELISA 20. Serum concentration of TCZ, up to 60 days measured using ELISA |
| Overall study start date | 10/03/2020 |
| Completion date | 28/07/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Both |
| Target number of participants | 450 |
| Total final enrolment | 452 |
| Key inclusion criteria | 1. Hospitalized with COVID-19 pneumonia confirmed per a positive PCR of any specimen (e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan 2. SPO₂ </=93% or PaO₂/FiO₂ <300 mmHg |
| Key exclusion criteria | 1. Known severe allergic reactions to TCZ or other monoclonal antibodies 2. Active tuberculosis (TB) infection 3. Suspected active bacterial, fungal, viral, or other infection (besides COVID-19) 4. In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments 5. Have received oral anti-rejection or immunomodulatory drugs (including TCZ) with the past 3 months 6. Participating in other drug clinical trials (participation in COVID-19 antiviral trials may be permitted if approved by Medical Monitor) 7. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination 8. Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization (investigational COVID-19 antivirals may be permitted if approved by Medial Monitor) 9. Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study 10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >10 x upper limit of normal (ULN) detected within 24 hours at screening (per local lab) 11. Absolute neutrophil count (ANC) < 1000/ml at screening (per local lab) 12. Platelet count < 50,000/mL at screening (per local lab) |
| Date of first enrolment | 03/04/2020 |
| Date of final enrolment | 28/05/2020 |
Locations
Countries of recruitment
- Canada
- Denmark
- France
- Germany
- Italy
- Netherlands
- Spain
- United Kingdom
- United States of America
Study participating centres
Houston
TX 77030
United States of America
United States of America
Sponsor information
Industry
1 DNA Way
South San Francisco
94080
United States of America
| Phone | +1 (0)888 662 6728 |
|---|---|
| global-roche-genentech-trials@gene.com | |
| Website | https://www.roche.com/about_roche/roche_worldwide.htm |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Genentech, Inc., Genentech USA, Inc., Genentech USA
- Location
- United States of America
Government organisation / National government
- Alternative name(s)
- BARDA
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/07/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Preprint results | non-peer-reviewed results in preprint | 12/09/2020 | 21/01/2021 | No | No |
| Results article | results | 25/02/2021 | 17/03/2021 | Yes | No |
Editorial Notes
17/03/2021: Publication reference added.
04/12/2020: Trial’s existence confirmed by West Midlands - Coventry & Warwickshire Research Ethics Committee.
