Covid19Phase 2ESsCOVIDNCT04576728
Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19
A Phase 2 study testing Trimodulin in people with Covid19, run by Biotest at 17 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Trimodulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 166 participants
- Where
- 17 sitesin 4 countries
- Study dates
- 6 Oct 2020to 29 Jun 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Male or female subject ≥18 years of age.
- Laboratory-confirmed SARS-CoV-2 infection from a test done in a respiratory tract sample within the last 5 days at screening.
- 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.
- Subject must receive SoC treatment for COVID-19.
Who cannot join
- Pregnant or lactating women.
- 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.
- Severe neutropenia (neutrophil count <500/mm³) assessed within 24 hours prior to start of treatment.
- Thrombocytopenia (platelet count <30,000/mm³) assessed within 24 hours prior to start of treatment.
- Hemoglobin <7g/dL assessed within 24 hours prior to start of treatment.
- Known hemolysis.
Show all 22Show fewer
- 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.
- 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).
- Subject with end stage renal disease (ESRD), or known primary focal segmental glomerulosclerosis (FSGS).
- 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).
- Known decompensated heart failure (New York Heart Association class III-IV).
- Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh C score ≥9 points), or hepatocellular carcinoma.
- Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin.
- Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA.
- Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months.
- Known human immunodeficiency virus infection.
- 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.
- Obesity (body mass index ≥40 kg/m²), a body weight of more than 123 kg, or anorexia (body mass index <16 kg/m²).
- Known immunosuppressive treatment other than acute treatment for COVID-19 (e.g. transplant recipient, subject with autoimmune disease).
- 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.
- Participation in another interventional clinical trial within 30 days before entering, or during the trial, or previous participation in this clinical trial.
- Employee or direct relative of an employee of the contract research organization, the trial site, or Biotest.
Trial locations and contacts
17 sites in 4 countries.
17 sites in 4 countries
Russia8 sites
Investigational site # 0707
Kemerovo, 650066
Investigational site # 0709
Krasnoyarsk, 660062
Investigational site # 0702
Moscow, 111539
Investigational site # 0706
Moscow, 119048
Investigational site # 0711
Moscow, 125015
Investigational Site # 0704
Moscow, 125367
Investigational site # 0708
Moscow, 129301
Investigational site # 0701
Saint Petersburg, 197706
Brazil4 sites
Investigational site # 5503
Porto Alegre, 90020-090
Investigational site # 5502
Santo André, 09030-010
Investigational site # 5505
Santo André, 09080-110
Investigational site # 5501
São Paulo, 05403-000
France3 sites
Investigational site # 3304
Paris, 75020
Investigational Site # 3301
Paris, 75877
Investigational site # 3305
Saint-Etienne, 42 055
Spain2 sites
Investigational Site # 3401
Barcelona
Investigational Site # 3402
Madrid
About this study
Official 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
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.
Read the detailed description
This is a randomized, placebo-controlled, double-blind, multi-center, phase II trial investigating the efficacy and safety of trimodulin compared to placebo treatment, as add-on therapy to SoC in adult subjects with severe COVID-19. Severe COVID-19 patients with need for non-invasive ventilation or high flow oxygen and with dysregulated inflammatory responses demonstrated by an elevated CRP level, will be enrolled.
Subjects will be randomized to receive either trimodulin or placebo on a 1:1 basis, stratified by center. Investigational Medicinal Product (IMP) treatments will be blinded. Subjects will be administered IMP once daily on five consecutive days (day 1 through day 5) as add-on therapy to SoC. The subsequent follow-up phase comprises 23 [+3] days (day 6 through day 28) followed by an end-of-trial visit/ telephone call on day 29 [+3]. For evaluation of this trial, a 9-category ordinal scale will be used. The primary aim of trimodulin treatment in the enrolled severely ill patients with a score of 5, is to prevent their clinical deterioration to a critical disease stage (score 6-7, e.g. requiring invasive mechanical ventilation or ECMO) and death (score 8). Accordingly, a composite primary efficacy endpoint reflecting the deterioration / mortality rate is used.
- Conditions
- Covid19
- Being tested
- Trimodulin, Placebo (human albumin 1%)
- Keywords
- Covid19, Severe community acquired pneumonia, Acute Respiratory Distress Syndrome, SARS-CoV-2, Severe Corona Virus Disease
- Medical subject headings
- COVID-19, Community-Acquired Pneumonia, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrimodulinDrug
Also called BT588
IMP will be administered via IV infusion on 5 consecutive days.
Placebo (human albumin 1%)Other
IMP will be administered via IV infusion on 5 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Trimodulin | Experimental | Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration. Receives: Drug: Trimodulin |
| Placebo | Placebo comparator | Human albumin 1% Receives: Other: Placebo (human albumin 1%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical detoriation rate
Percentage of subjects with a change of clinical status to score 6 or 7 on the 9-category ordinal scale
Measured: Between day 6 and day 29
28-day all-cause mortality rate
Percentage of subjects with a change to score 8 on the 9-category ordinal scale
Measured: Between day 1 and day 29
Secondary outcomes (20)
Clinical deterioration rate
Percentage of subjects with a change to score 6-7
Measured: Days 1-29 and days 6-29
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].
Measured: Day 29
Time to clinical deterioration
Number of days to first change from score 5 (enrollment) to score 6-7
Measured: Time Frame: between Days 1-29 and days 6-29
Time to Mortality
Number of days to change to score =8
Measured: Time Frame: between Day 1 and day 29
Proportion of subjects in each of the 9-categories of the ordinal scale
Number of patients by score on specific study days
Measured: Days 7, 14, 21, 29
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)
Measured: Day 29
Proportion of subjects with score ≤2
Proporation of subjects that improved to score ≤2
Measured: Day 29
Days on IMV
Number of calendar days on IMV until day 29
Measured: Until day 29
Days without oxygen supply
Number of calendar days without any form of oxygen support until day 29
Measured: Until day 29
Time to discontinuation from any form of oxygen supply
Time to definite stop of any form of additional oxygenation, irrespective of short interruptions
Measured: Until day 29
Proportion of subjects without any form of oxygen supply
Proportion of subjects that improved to not requiring supplemental oxygen.
Measured: Day 29
Hospital-free-days
Calendar days between hospital discharge and day 29
Measured: Until day 29
SARS-CoV-2 status
Time to SARS-CoV-2 negative status
Measured: Until day 29
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.
Measured: Until day 29
TEAEs
Number of all infusion related TEAEs
Measured: Until day 29
SAEs
Number, severity, causality, and outcome of all SAEs
Measured: Until day 29
Dose modifications
Dose modifications (incl. reductions and changes in infusion rate)
Measured: Day 1-5
Time to recovery
Number of days to change to score ≤2 (hospital discharged or meets discharge criteria)
Measured: Day 29
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.
Measured: Until day 29
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.
Measured: Until day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2020
- Study start6 Oct 2020
- Primary completion29 Jun 2021
- Study completion29 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies 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
- Model description
- Subjects will be randomized on a 1:1 basis either to trimodulin or to placebo treatment stratified by center.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biotest
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Antoni Torres, MD, Principal investigator, University of Barcelona Hospital Clinic of Barcelona Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04576728
- Sponsor's protocol ID
- 998
- Acronym
- ESsCOVID
- Status last verified
- Jan 2023
- First submitted
- 24 Sep 2020
- Last updated
- 10 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Agafina A, Aguiar VC, Rossovskaya M, Fartoukh MS, Hajjar LA, Thiery G, Timsit JF, Gordeev I, Protsenko D, Carbone J, Pellegrini R, Stadnik CMB, Avdeev S, Ferrer M, Heinz CC, Hader T, Langohr P, Bobenhausen I, Schuttrumpf J, Staus A, Ruehle M, Weissmuller S, Wartenburg-Demand A, Torres A. Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID). Eur J Med Res. 2024 Aug 13;29(1):418. doi: 10.1186/s40001-024-02008-x.
PubMed 39138518
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04576728
- Acronym / sponsor ID
- ESsCOVID / 998
- Conditions
- Covid19
- Keywords
- Covid19, Severe community acquired pneumonia, Acute Respiratory Distress Syndrome, SARS-CoV-2, Severe Corona Virus Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- BiotestIndustry (pharma, biotech, devices)
- Study start
- 6 Oct 2020 (actual)
- Primary completion
- 29 Jun 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 6 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a randomized, placebo-controlled, double-blind, multi-center, phase II trial investigating the efficacy and safety of trimodulin compared to placebo treatment, as add-on therapy to SoC in adult subjects with severe COVID-19. Severe COVID-19 patients with need for non-invasive ventilation or high flow oxygen and with dysregulated inflammatory responses demonstrated by an elevated CRP level, will be enrolled.
Subjects will be randomized to receive either trimodulin or placebo on a 1:1 basis, stratified by center. Investigational Medicinal Product (IMP) treatments will be blinded. Subjects will be administered IMP once daily on five consecutive days (day 1 through day 5) as add-on therapy to SoC. The subsequent follow-up phase comprises 23 [+3] days (day 6 through day 28) followed by an end-of-trial visit/ telephone call on day 29 [+3]. For evaluation of this trial, a 9-category ordinal scale will be used. The primary aim of trimodulin treatment in the enrolled severely ill patients with a score of 5, is to prevent their clinical deterioration to a critical disease stage (score 6-7, e.g. requiring invasive mechanical ventilation or ECMO) and death (score 8). Accordingly, a composite primary efficacy endpoint reflecting the deterioration / mortality rate is used.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized on a 1:1 basis either to trimodulin or to placebo treatment stratified by center.
| Arm | Type | Receives |
|---|---|---|
| Trimodulin | Experimental | Drug: TrimodulinTrimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration. |
| Placebo | Placebo comparator | Other: Placebo (human albumin 1%)Human albumin 1% |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- Male or female subject ≥18 years of age.
- Laboratory-confirmed SARS-CoV-2 infection from a test done in a respiratory tract sample within the last 5 days at screening.
- 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).
Key exclusion criteria (22 listed)
- Pregnant or lactating women.
- 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.
- Severe neutropenia (neutrophil count <500/mm³) assessed within 24 hours prior to start of treatment.
- Thrombocytopenia (platelet count <30,000/mm³) assessed within 24 hours prior to start of treatment.
- Hemoglobin <7g/dL assessed within 24 hours prior to start of treatment.
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 |
|---|---|---|
| TrimodulinAlso: BT588IMP will be administered via IV infusion on 5 consecutive days. | Drug | Trimodulin |
| Placebo (human albumin 1%)IMP will be administered via IV infusion on 5 consecutive days. | Other | Placebo |
Primary outcome
Clinical detoriation rate
Time frame: Between day 6 and day 29
Percentage of subjects with a change of clinical status to score 6 or 7 on the 9-category ordinal scale
28-day all-cause mortality rate
Time frame: Between day 1 and day 29
Percentage of subjects with a change to score 8 on the 9-category ordinal scale
20 secondary outcomes
Clinical deterioration rate
Time frame: Days 1-29 and days 6-29
28-days all-cause mortality rate on day 29
Time frame: Day 29
Time to clinical deterioration
Time frame: Time Frame: between Days 1-29 and days 6-29
Time to Mortality
Time frame: Time Frame: between Day 1 and day 29
Proportion of subjects in each of the 9-categories of the ordinal scale
Time frame: Days 7, 14, 21, 29
Time to clinical improvement
Time frame: Day 29
Proportion of subjects with score ≤2
Time frame: Day 29
Days on IMV
Time frame: Until day 29
Days without oxygen supply
Time frame: Until day 29
Time to discontinuation from any form of oxygen supply
Time frame: Until day 29
Proportion of subjects without any form of oxygen supply
Time frame: Day 29
Hospital-free-days
Time frame: Until day 29
SARS-CoV-2 status
Time frame: Until day 29
Adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest, infusional TEAEs
Time frame: Until day 29
TEAEs
Time frame: Until day 29
SAEs
Time frame: Until day 29
Dose modifications
Time frame: Day 1-5
Time to recovery
Time frame: Day 29
Change over time in ECG parameters
Time frame: Until day 29
Change over time in vital signs
Time frame: Until day 29
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2023.
- Derived from this study: PubMed 39138518Agafina A, Aguiar VC, Rossovskaya M, Fartoukh MS, Hajjar LA, Thiery G, Timsit JF, Gordeev I, Protsenko D, Carbone J, Pellegrini R, Stadnik CMB, Avdeev S, Ferrer M, Heinz CC, Hader T, Langohr P, Bobenhausen I, Schuttrumpf J, Staus A, Ruehle M, Weissmuller S, Wartenburg-Demand A, Torres A. Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID). Eur J Med Res. 2024 Aug 13;29(1):418. doi: 10.1186/s40001-024-02008-x.
- Individual participant dataSharing planned: No
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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.
Antoni Torres, MD principal investigator
University of Barcelona Hospital Clinic of Barcelona Spain
17 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trimodulin in people with Covid19, run by Biotest at 17 sites in 4 countries.
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 8 inclusion and 22 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 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Russia, Brazil, France, Spain. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical detoriation rate (time frame: Between day 6 and day 29). The study lists 2 primary outcomes in all. 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 NCT04576728, 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 10 Jan 2023.