Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19 (ESsCOVID)
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|ClinicalTrials.gov Identifier: NCT04576728|
Recruitment Status : Active, not recruiting
First Posted : October 6, 2020
Last Update Posted : June 16, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Covid19||Drug: Trimodulin Other: Placebo (human albumin 1%)||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||164 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Subjects will be randomized on a 1:1 basis either to trimodulin or to placebo treatment stratified by center.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||All bottles will be indistinguishable.|
|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|
|Actual Study Start Date :||October 6, 2020|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2021|
Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.
IMP will be administered via IV infusion on 5 consecutive days.
Other Name: BT588
Placebo Comparator: Placebo
Human albumin 1%
Other: Placebo (human albumin 1%)
IMP will be administered via IV infusion on 5 consecutive days.
- 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
- Clinical deterioration rate [ Time Frame: Days 1-29 and days 6-29 ]Percentage of subjects with a change to score 6-7
- 28-days all-cause mortality rate on day 29 [ Time Frame: Day 29 ]Percentage of subjects with score=8, assessed at the end-of-trial visit on day 29 [+3].
- Time to clinical deterioration [ Time Frame: Time Frame: between Days 1-29 and days 6-29 ]Number of days to first change from score 5 (enrollment) to score 6-7
- Time to Mortality [ Time Frame: Time Frame: between Day 1 and day 29 ]Number of days to change to score =8
- Proportion of subjects in each of the 9-categories of the ordinal scale [ Time Frame: Days 7, 14, 21, 29 ]Number of patients by score on specific study days
- Time to clinical improvement [ Time Frame: Day 29 ]Number of days to change to score 4 (mild disease, with supplemental oxygen) or score 3 (mild disease, no supplemental oxygen)
- Proportion of subjects with score ≤2 [ Time Frame: Day 29 ]Proporation of subjects that improved to score ≤2
- Days on IMV [ Time Frame: Until day 29 ]Number of calendar days on IMV until day 29
- Days without oxygen supply [ Time Frame: Until day 29 ]Number of calendar days without any form of oxygen support until day 29
- Time to discontinuation from any form of oxygen supply [ Time Frame: Until day 29 ]Time to definite stop of any form of additional oxygenation, irrespective of short interruptions
- Proportion of subjects without any form of oxygen supply [ Time Frame: Day 29 ]Proportion of subjects that improved to not requiring supplemental oxygen.
- Hospital-free-days [ Time Frame: Until day 29 ]Calendar days between hospital discharge and day 29
- SARS-CoV-2 status [ Time Frame: Until day 29 ]Time to SARS-CoV-2 negative status
- Adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest, infusional TEAEs [ Time Frame: Until day 29 ]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.
- TEAEs [ Time Frame: Until day 29 ]Number of all infusion related TEAEs
- SAEs [ Time Frame: Until day 29 ]Number, severity, causality, and outcome of all SAEs
- Dose modifications [ Time Frame: Day 1-5 ]Dose modifications (incl. reductions and changes in infusion rate)
- Time to recovery [ Time Frame: Day 29 ]Number of days to change to score ≤2 (hospital discharged or meets discharge criteria)
- Change over time in ECG parameters [ Time Frame: Until day 29 ]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.
- Change over time in vital signs [ Time Frame: Until day 29 ]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.
- Pharmacokinetic assessment of immunoglobulins [ Time Frame: Day 1(baseline) to day 29 ]Assessment of changes in serum concentrations (g/L) of IgM, IgA, and IgG before, during and after treatment.
- Pharmacodynamic assessment of disease related serum proteins [ Time Frame: Day 1(baseline) to day 29 ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04576728
|Principal Investigator:||Antoni Torres, MD||University of Barcelona Hospital Clinic of Barcelona Spain|