Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19

NCT04576728 | Completed Phase 2 DMC

• 1 other identifier: 998
• Study Type: interventional
• Target: 166
• Locations: 4 countries
• Sites: 17

Brief 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. Additionally, pharmacodynamic (PD) and pharmacokinetic (PK) properties of trimodulin will be evaluated in all subjects.

Conditions

Covid19

Keywords

Covid19; Severe community acquired pneumonia; Acute Respiratory Distress Syndrome; SARS-CoV-2; Severe Corona Virus Disease

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (20)

• Clinical deterioration rate

  Days 1-29 and days 6-29

• 28-days all-cause mortality rate on day 29

  Day 29

• Time to clinical deterioration

  Time Frame: between Days 1-29 and days 6-29

• Time to Mortality

  Time Frame: between Day 1 and day 29

• Proportion of subjects in each of the 9-categories of the ordinal scale

  Days 7, 14, 21, 29

Other Outcomes (2)

• Pharmacokinetic assessment of immunoglobulins

  Day 1(baseline) to day 29

• Pharmacodynamic assessment of disease related serum proteins

  Day 1(baseline) to day 29

Study Arms (2)

Trimodulin

EXPERIMENTAL

Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.

Drug: Trimodulin

Placebo

PLACEBO COMPARATOR

Human albumin 1%

Other: Placebo (human albumin 1%)

Interventions

Trimodulin DRUG

IMP will be administered via IV infusion on 5 consecutive days.

Also known as: BT588

Trimodulin

Placebo (human albumin 1%) OTHER

IMP will be administered via IV infusion on 5 consecutive days.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Biotest: lead

Study Sites (17)

Investigational site # 5503

Porto Alegre, 90020-090, Brazil

Location

Investigational site # 5502

Santo André, 09030-010, Brazil

Location

Investigational site # 5505

Santo André, 09080-110, Brazil

Location

Investigational site # 5501

São Paulo, 05403-000, Brazil

Location

Investigational site # 3304

Paris, 75020, France

Location

Investigational Site # 3301

Paris, 75877, France

Location

Investigational site # 3305

Saint-Etienne, 42 055, France

Location

Investigational site # 0707

Kemerovo, 650066, Russia

Location

Investigational site # 0709

Krasnoyarsk, 660062, Russia

Location

Investigational site # 0702

Moscow, 111539, Russia

Location

Investigational site # 0706

Moscow, 119048, Russia

Location

Investigational site # 0711

Moscow, 125015, Russia

Location

Investigational Site # 0704

Moscow, 125367, Russia

Location

Investigational site # 0708

Moscow, 129301, Russia

Location

Investigational site # 0701

Saint Petersburg, 197706, Russia

Location

Investigational Site # 3401

Barcelona, Spain

Location

Investigational Site # 3402

Madrid, Spain

Location

Related Publications (1)

• 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.

  PMID: 39138518 DERIVED

MeSH Terms

Conditions

COVID-19; Community-Acquired Pneumonia; Respiratory Distress Syndrome

Interventions

trimodulin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Community-Acquired Infections; Respiration Disorders

Study Officials

• Antoni Torres, MD

  University of Barcelona Hospital Clinic of Barcelona Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All bottles will be indistinguishable.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized on a 1:1 basis either to trimodulin or to placebo treatment stratified by center.

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: October 6, 2020
• Study Start: October 6, 2020
• Primary Completion: June 29, 2021
• Study Completion: June 29, 2021
• Last Updated: January 10, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

RU (8); ES (2); BR (4); FR (3)