Covid19 Clinical Trial
— ESsCOVIDOfficial title:
A Randomized, Placebo-controlled, Double-blind, Multi-center, Phase II Trial Investigating the Efficacy and Safety of Trimodulin (BT588) as add-on Therapy to Standard of Care in Adult Subjects With Severe COVID-19
NCT number | NCT04576728 |
Other study ID # | 998 |
Secondary ID | |
Status | Completed |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | October 6, 2020 |
Est. completion date | June 29, 2021 |
Verified date | January 2023 |
Source | Biotest |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The objectives of the trial are to evaluate the efficacy and safety of trimodulin as add-on therapy to standard of care (SoC) compared to placebo treatment in adult hospitalized subjects with severe COVID-19. Additionally, pharmacodynamic (PD) and pharmacokinetic (PK) properties of trimodulin will be evaluated in all subjects.
Status | Completed |
Enrollment | 166 |
Est. completion date | June 29, 2021 |
Est. primary completion date | June 29, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Written informed consent obtained from the subject or legally authorized representative or informed verbal or administration consent due to pandemic situation, in compliance with all local legal requirements. 2. Male or female subject =18 years of age. 3. Laboratory-confirmed SARS-CoV-2 infection from a test done in a respiratory tract sample within the last 5 days at screening. 4. Diagnosis of community-acquired severe COVID-19 within 10 days after hospital-admission, with severe defined as: Need for non-invasive ventilation (NIV), or high-flow oxygen therapy (score =5 on the 9-category ordinal scale). At least one of the following clinical respiratory parameters is fulfilled: dyspnea, respiratory frequency =30/min, SpO2 =93%, 100 mmHg < PaO2/FiO2 =300 mmHg, and/or lung infiltrates >50% within 24 to 48 hours. At least one measurement of C-reactive protein =50 mg/L within 36 hours prior to start of treatment. 5. Subject must receive SoC treatment for COVID-19. Exclusion Criteria: 1. Pregnant or lactating women. 2. Subjects that deteriorated to score >5 on the 9-category ordinal scale (e.g. receiving invasive mechanical ventilation (IMV), and/or extracorporeal membrane oxygenation (ECMO)) or subjects that improved to score <5 prior to randomization. 3. Severe neutropenia (neutrophil count <500/mm³) assessed within 24 hours prior to start of treatment. 4. Thrombocytopenia (platelet count <30,000/mm³) assessed within 24 hours prior to start of treatment. 5. Hemoglobin <7g/dL assessed within 24 hours prior to start of treatment. 6. Known hemolysis. 7. Known thrombosis or thromboembolic events (TEEs) or known medical history of TEEs (e.g. cerebrovascular accidents, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep vein thrombosis) within the previous 3 months or those subjects particularly at risk for TEEs (e.g. history of thrombophilia, permanent immobilization, or permanent paralysis of the lower extremities) caused by other reasons than COVID-19. 8. Subject on dialysis or with severe renal impairment, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² assessed within 24 hours prior to start of treatment (details in Appendix 3: Estimated Glomerular Filtration Rate). 9. Subject with end stage renal disease (ESRD), or known primary focal segmental glomerulosclerosis (FSGS). 10. Known severe lung diseases interfering with COVID-19 therapy (e.g. severe interstitial lung disease, cystic fibrosis, idiopathic pulmonary fibrosis, active tuberculosis, chronically infected bronchiectasis, or active lung cancer). 11. Known decompensated heart failure (New York Heart Association class III-IV). 12. Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh C score =9 points), or hepatocellular carcinoma. 13. Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin. 14. Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA. 15. Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months. 16. Known human immunodeficiency virus infection. 17. Life expectancy of less than 90 days, according to the Investigator's clinical judgment, because of medical conditions neither related to COVID-19 nor to associated medical complications. 18. Obesity (body mass index =40 kg/m²), a body weight of more than 123 kg, or anorexia (body mass index <16 kg/m²). 19. Known immunosuppressive treatment other than acute treatment for COVID-19 (e.g. transplant recipient, subject with autoimmune disease). 20. Known treatment with polyvalent immunoglobulin preparations, any type of blood product, or any type of interferon during the last 21 days before entering the trial. 21. Participation in another interventional clinical trial within 30 days before entering, or during the trial, or previous participation in this clinical trial. 22. Employee or direct relative of an employee of the contract research organization, the trial site, or Biotest. |
Country | Name | City | State |
---|---|---|---|
Brazil | Investigational site # 5503 | Porto Alegre | |
Brazil | Investigational site # 5502 | Santo André | |
Brazil | Investigational site # 5505 | Santo André | |
Brazil | Investigational site # 5501 | São Paulo | |
France | Investigational Site # 3301 | Paris | |
France | Investigational site # 3304 | Paris | |
France | Investigational site # 3305 | Saint-Étienne | |
Russian Federation | Investigational site # 0707 | Kemerovo | |
Russian Federation | Investigational site # 0709 | Krasnoyarsk | |
Russian Federation | Investigational site # 0702 | Moscow | |
Russian Federation | Investigational Site # 0704 | Moscow | |
Russian Federation | Investigational site # 0706 | Moscow | |
Russian Federation | Investigational site # 0708 | Moscow | |
Russian Federation | Investigational site # 0711 | Moscow | |
Russian Federation | Investigational site # 0701 | Saint Petersburg | |
Spain | Investigational Site # 3401 | Barcelona | |
Spain | Investigational Site # 3402 | Madrid |
Lead Sponsor | Collaborator |
---|---|
Biotest |
Brazil, France, Russian Federation, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Pharmacokinetic assessment of immunoglobulins | Assessment of changes in serum concentrations (g/L) of IgM, IgA, and IgG before, during and after treatment. | Day 1(baseline) to day 29 | |
Other | Pharmacodynamic assessment of disease related serum proteins | Assessment of relative changes in serum concentrations from baseline before, during and after treatment including inflammation markers (e.g. % change in CRP, PCT, Ferritin, TNF-alpha, IL-6, IL-8 and IL-10), biomarkers (e.g. % change in p-selectin) and complement factors (e.g. % change in C3, C4). | Day 1(baseline) to day 29 | |
Primary | Clinical detoriation rate | Percentage of subjects with a change of clinical status to score 6 or 7 on the 9-category ordinal scale | Between day 6 and day 29 | |
Primary | 28-day all-cause mortality rate | Percentage of subjects with a change to score 8 on the 9-category ordinal scale | Between day 1 and day 29 | |
Secondary | Clinical deterioration rate | Percentage of subjects with a change to score 6-7 | Days 1-29 and days 6-29 | |
Secondary | 28-days all-cause mortality rate on day 29 | Percentage of subjects with score=8, assessed at the end-of-trial visit on day 29 [+3]. | Day 29 | |
Secondary | Time to clinical deterioration | Number of days to first change from score 5 (enrollment) to score 6-7 | Time Frame: between Days 1-29 and days 6-29 | |
Secondary | Time to Mortality | Number of days to change to score =8 | Time Frame: between Day 1 and day 29 | |
Secondary | Proportion of subjects in each of the 9-categories of the ordinal scale | Number of patients by score on specific study days | Days 7, 14, 21, 29 | |
Secondary | Time to clinical improvement | Number of days to change to score 4 (mild disease, with supplemental oxygen) or score 3 (mild disease, no supplemental oxygen) | Day 29 | |
Secondary | Proportion of subjects with score =2 | Proporation of subjects that improved to score =2 | Day 29 | |
Secondary | Days on IMV | Number of calendar days on IMV until day 29 | Until day 29 | |
Secondary | Days without oxygen supply | Number of calendar days without any form of oxygen support until day 29 | Until day 29 | |
Secondary | Time to discontinuation from any form of oxygen supply | Time to definite stop of any form of additional oxygenation, irrespective of short interruptions | Until day 29 | |
Secondary | Proportion of subjects without any form of oxygen supply | Proportion of subjects that improved to not requiring supplemental oxygen. | Day 29 | |
Secondary | Hospital-free-days | Calendar days between hospital discharge and day 29 | Until day 29 | |
Secondary | SARS-CoV-2 status | Time to SARS-CoV-2 negative status | Until day 29 | |
Secondary | Adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest, infusional TEAEs | Number, severity, causality, outcome, and seriousness of all. AE, TEAEs that led to permanent withdrawal of IMP, and TEAEs that led to discontinuation of the trial. | Until day 29 | |
Secondary | TEAEs | Number of all infusion related TEAEs | Until day 29 | |
Secondary | SAEs | Number, severity, causality, and outcome of all SAEs | Until day 29 | |
Secondary | Dose modifications | Dose modifications (incl. reductions and changes in infusion rate) | Day 1-5 | |
Secondary | Time to recovery | Number of days to change to score =2 (hospital discharged or meets discharge criteria) | Day 29 | |
Secondary | Change over time in ECG parameters | ECG recordings, (including heart rate, PR interval, RR interval, QRS interval, QT-interval, QTcF) showing abnormal, clinically relevant findings will be reported as adverse event. | Until day 29 | |
Secondary | Change over time in vital signs | Changes in recordings of vital sign parameters (including systolic and diastolic blood pressure, Arterial oxygen saturation, heart rate, respiratory rate and body temperature) showing clinically significant measurements outside the normal range will be reported as adverse event. | Until day 29 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05047692 -
Safety and Immunogenicity Study of AdCLD-CoV19-1: A COVID-19 Preventive Vaccine in Healthy Volunteers
|
Phase 1 | |
Recruiting |
NCT04395768 -
International ALLIANCE Study of Therapies to Prevent Progression of COVID-19
|
Phase 2 | |
Completed |
NCT04508777 -
COVID SAFE: COVID-19 Screening Assessment for Exposure
|
||
Completed |
NCT04506268 -
COVID-19 SAFE Enrollment
|
N/A | |
Terminated |
NCT04555096 -
A Trial of GC4419 in Patients With Critical Illness Due to COVID-19
|
Phase 2 | |
Completed |
NCT04961541 -
Evaluation of the Safety and Immunogenicity of Influenza and COVID-19 Combination Vaccine
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04546737 -
Study of Morphological, Spectral and Metabolic Manifestations of Neurological Complications in Covid-19 Patients
|
N/A | |
Terminated |
NCT04581915 -
PHRU CoV01 A Trial of Triazavirin (TZV) for the Treatment of Mild-moderate COVID-19
|
Phase 2/Phase 3 | |
Completed |
NCT04494646 -
BARCONA: A Study of Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19)
|
Phase 2 | |
Not yet recruiting |
NCT04543006 -
Persistence of Neutralizing Antibodies 6 and 12 Months After a Covid-19
|
N/A | |
Completed |
NCT04532294 -
Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/COVID-19) Neutralizing Antibody in Healthy Participants
|
Phase 1 | |
Terminated |
NCT04542993 -
Can SARS-CoV-2 Viral Load and COVID-19 Disease Severity be Reduced by Resveratrol-assisted Zinc Therapy
|
Phase 2 | |
Not yet recruiting |
NCT04527211 -
Effectiveness and Safety of Ivermectin for the Prevention of Covid-19 Infection in Colombian Health Personnel
|
Phase 3 | |
Completed |
NCT04387292 -
Ocular Sequelae of Patients Hospitalized for Respiratory Failure During the COVID-19 Epidemic
|
N/A | |
Completed |
NCT04537663 -
Prevention Of Respiratory Tract Infection And Covid-19 Through BCG Vaccination In Vulnerable Older Adults
|
Phase 4 | |
Completed |
NCT04507867 -
Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III
|
N/A | |
Completed |
NCT04979858 -
Reducing Spread of COVID-19 in a University Community Setting: Role of a Low-Cost Reusable Form-Fitting Fabric Mask
|
N/A | |
Not yet recruiting |
NCT05038449 -
Study to Evaluate the Efficacy and Safety of Colchicine Tablets in Patients With COVID-19
|
N/A | |
Completed |
NCT04610502 -
Efficacy and Safety of Two Hyperimmune Equine Anti Sars-CoV-2 Serum in COVID-19 Patients
|
Phase 2 | |
Active, not recruiting |
NCT06042855 -
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin)
|
Phase 3 |