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A Study to Evaluate the Safety and Effect of STC3141 Continuous Infusion in Subjects With Severe Corona Virus Disease 2019(COVID-19)Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04880694
Recruitment Status : Recruiting
First Posted : May 11, 2021
Last Update Posted : June 14, 2021
Sponsor:
Collaborator:
Trium Clinical Consulting
Information provided by (Responsible Party):
Grand Medical Pty Ltd.

Brief Summary:
The study is a Randomized, Open-Label, Multi-Centre, Phase 2a Study to Evaluate the Safety and Effect of STC3141 Continuous Infusion in Subjects with Severe Corona Virus Disease 2019(COVID-19)Pneumonia.

Condition or disease Intervention/treatment Phase
Severe COVID-19 Pneumonia Drug: STC3141 Phase 2

Detailed Description:

Pneumonia is the most frequent and serious complication of Corona Virus Disease 2019(COVID-19), a disease that results from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection with a so-called "cytokine storm", characterized by the plasma increase of many cytokines that produce long-term damage and fibrosis of lung tissue. Therefore, the development of novel therapeutic strategies to target at neutrophils associated NETs/histones may reduce the overall disease mortality rate of COVID-19.

STC3141 is a novel investigational product that can neutralize NETs/histone via charge-charge interaction. STC3141 was found to be well-tolerated in short infusions (2 hours) and continuous long-term infusions (72 hours) in healthy volunteers.

A randomized, multi-centre, phase 2a study in 25 severe COVID-19 pneumonia subjects who require hospitalization, is designed to evaluate the safety and the preliminary effect of STC3141 in this population where the treatment will be tested for the first time.

Subjects will be randomized to three cohorts in a 2:2:1 ratio to receive continuous infusion of STC3141 either at rate 58.3mg/hr or 87.5mg/hr up to 3 days (72hours), or to receive appropriate standard of care. All subjects in STC3141 treatment groups will also receive standard of care for their conditions as background treatment.

The primary objective of the study is to evaluate the safety of STC3141 in subjects with severe COVID-19 pneumonia.The secondary objective is to evaluate the preliminary effects of STC3141 in the treatment of subjects with severe COVID-19 pneumonia.As an exploratory objective, the change in biomarkers from baseline following STC3141 treatment in subjects with severe COVID-19 pneumonia will be evaluated.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized to three cohorts in a 2:2:1 ratio to receive continuous infusion of STC3141 either at rate 58.3mg/hr or 87.5mg/hr up to 3 days (72hours), or to receive appropriate standard of care. All subjects in STC3141 treatment groups will also receive standard of care for their conditions as background treatment.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Multi-Centre, Phase 2a Study to Evaluate the Safety and Effect of STC3141 Continuous Infusion in Subjects With Severe Corona Virus Disease 2019(COVID-19)Pneumonia
Actual Study Start Date : May 20, 2021
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: STC3141 58.3mg/hr
Drug: STC3141 Continuous infusion of STC3141 at rate 58.3mg/hr up to 3 days (72 hours) N=10
Drug: STC3141

To receive continuous infusion of STC3141 at rate 58.3mg/hr up to 3 days (72hours).

Also to receive appropriate standard of care.


Experimental: Cohort 2: STC3141 87.5mg/hr
Drug: STC3141 Continuous infusion of STC3141 at rate 87.5mg/hr up to 3 days (72 hours) N=10
Drug: STC3141

To receive continuous infusion of STC3141 at rate 87.5mg/hr up to 3 days (72hours).

Also to receive appropriate standard of care.


No Intervention: Cohort 3: Comparator
Only to receive appropriate standard of care N=5



Primary Outcome Measures :
  1. The incidence of adverse event(AE), treatment emergent adverse event(TEAE), serious adverse event(SAE), adverse event of special interest(AESI) [ Time Frame: up to 30 days ]

Secondary Outcome Measures :
  1. Changes of C-reactive protein(CRP)(mg/dL, or nmol/L, or mg/L) [ Time Frame: through study completion, an average of 30 days. ]
  2. Changes of D-dimer(mg/L, or ng/mL, or μg/mL) [ Time Frame: through study completion, an average of 30 days. ]
  3. Changes of total bleeding time(TBL)(μmol/L) [ Time Frame: through study completion, an average of 30 days. ]
  4. Changes alanine transaminase(ALT)(IU/L, or U/L, or nkat/L) [ Time Frame: through study completion, an average of 30 days. ]
  5. Changes estimated glomerular filtration rate(eGFR)(ml/min) [ Time Frame: through study completion, an average of 30 days. ]
  6. Changes of activated partial thromboplastin time(aPTT)(seconds) [ Time Frame: through study completion, an average of 30 days. ]
  7. Changes of lactate dehydrogenase(LDH)(IU/L, or U/L, or nkat/L) [ Time Frame: through study completion, an average of 30 days. ]
  8. Changes of partial pressure of oxygen(PaO2)/fraction of inspired oxygen(FiO2) ratio [ Time Frame: through study completion, an average of 30 days. ]
  9. Changes of partial pressure of oxygen(PaO2)/fraction of inspired oxygen(FiO2) ratio for subjects who are on invasive or non-invasive ventilator [ Time Frame: through study completion, an average of 30 days. ]
  10. Changes of Sequential Organ Failure Assessment(SOFA)score [ Time Frame: through study completion, an average of 30 days. ]
    Specific score of 0, 1, 2, 3, 4. Higher score indicates worse prognosis.

  11. Time to invasive mechanical ventilation [ Time Frame: through study completion, an average of 30 days. ]
  12. Time to independence from non-invasive mechanical ventilation [ Time Frame: through study completion, an average of 30 days. ]
  13. Time to independence from oxygen therapy [ Time Frame: through study completion, an average of 30 days. ]
  14. Duration of hospitalization [ Time Frame: through study completion, an average of 30 days. ]
  15. All-cause mortality rate [ Time Frame: On Day 30. ]
  16. Subgroup analysis [ Time Frame: through study completion, an average of 30 days. ]

Other Outcome Measures:
  1. Changes from baseline in MPO(neutrophil-derived extracellular traps (NETs))(ng/ml)and citrullinated histone (H3 in plasma)(ng/ml) [ Time Frame: up to 7 days ]
    As an exploratory objective, the change in biomarkers from baseline following STC3141 treatment in subjects with severe COVID-19 pneumonia will be evaluated.

  2. Changes from baseline in interleukin(IL)-1b, interleukin(IL)-2, interleukin(IL)-6, interleukin(IL)-8/CXCL8, interleukin(IL)-10, Interferon(IFN)-γ, tumor necrosis factor(TNF)-α, interleukin(IL)-12/P70(pg/ml) [ Time Frame: up to 7 days ]
    As an exploratory objective, the change in biomarkers from baseline following STC3141 treatment in subjects with severe COVID-19 pneumonia will be evaluated.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and non-pregnant females who are 18 years or older (inclusive).
  2. Signed informed consent. Subjects are to provide informed consent prior to any study procedures being performed. Consent can be oral if a written consent cannot be expressed. Where it is not practicable to approach a subject highly dependent on medical care, or the subject is not capable of making such a decision, consent will be sought from the legal representative of the subject. Subjects enrolled in the study based on consent by the legal representative will be given the opportunity to provide written confirmatory consent when and if they become able to do so. If the subject declines to confirm consent, they will be withdrawn from the study at the point where they decline consent.
  3. Virological diagnosis of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection (documentation of real-time polymerase chain reaction(PCR)or equivalent within the last 72h positive results is available before screening)
  4. Hospitalized due to clinical/chest image diagnosis of sever pneumonia. Severe pneumonia defined as dyspnea, hemoglobin oxygen saturation(SpO2)on room air at rest ≤93% or Partial pressure of oxygen(PaO2)/Fraction of inspired oxygen(FiO2)<300 mmHg.

Exclusion Criteria:

  1. Subjects who have renal impairment at screening, defined as an estimate glomerular filtration rate (eGFR) <55 ml/min/Body Surface area(BSA)
  2. Subjects requiring extracorporeal membrane oxygenation (ECMO) at screening
  3. Subjects who are on invasive mechanical ventilator more than 24 hours
  4. Female subjects of child-bearing potential (as judged by the Investigator) who do not agree to remain abstinent or use medically acceptable methods of contraception (e.g., implants, injectable, combined oral contraceptives, intra-uterine devices [Intrauterine devices(IUDs)], double-barrier protection) during the study. Male participants who do not agree to use a condom with spermicide during intercourse (if not surgically sterilized) during the study.
  5. Subjects who receive anticoagulants overall (except subtherapeutic doses of heparin which is ≤ 6000 International Unit(IU)twice a day Enoxaparin or equivalence) including but not limited to warfarin, rivaroxaban, apixaban, dabigatran acenocoumarol, fencoumarol, or other parenteral anticoagulants at randomization. Antiplatelets drugs are allowed
  6. Subjects who have International Normalized ratio or International normalized ratio(INR)>1.3 Upper limit of normal(ULN).
  7. Subjects who have Absolute Neutrophil Count (ANC) <1,000/μL.
  8. Subjects who have platelets count <80,000 /μL.
  9. Subjects who have activated Partial Thromboplastin Time (aPTT) >1.5 Upper limit of normal(ULN).
  10. Severe anaemia (haemoglobin < 7.0 g/dL).
  11. Bleeding in the past 24 hours requiring blood transfusion.
  12. Women who are pregnant or lactating at Screening or planning to conceive (self or partner) at any time during the study, including the follow-up period.
  13. Subjects who have the following chronic organ dysfunction or immunosuppression:

    1. Heart: New York heart association cardiac function IV.
    2. Lung: severe lung diseases other than COVID-19 lead to home oxygen therapy.
    3. Kidneys: renal impairment requiring chronic dialysis
    4. Liver: liver cirrhosis confirmed by biopsy and clear portal hypertension; the upper digestive tract hemorrhage caused by portal hypertension; or previous liver failure/hepatic encephalopathy/hepatic coma.
    5. Immune function: IV chemotherapy and radiotherapy within 4 weeks before screening or use of immunosuppressive medication within 2 weeks before screening including but not limited to: tacrolimus, cyclosporin, sirolimus, mycophenolate or azathioprine etc., or subjects with leukemia, lymphoma or acquired immunodeficiency syndrome [AIDS].
  14. Solid organ or bone marrow transplantation within 4 weeks.
  15. The following conditions occurring within 4 weeks prior to screening:

    1. Acute pulmonary embolism
    2. Acute coronary syndrome such as myocardial infarction, unstable angina pectoris etc.
  16. Known allergy to the active ingredient of STC3141 or its excipients (i.e., phosphate buffer).
  17. The investigator consider participation in the study is not in the best interests of the subjects.
  18. Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator's (or delegate's) opinion, could adversely affect the safety of the subject; affect study endpoints or decrease the chance of obtaining satisfactory data required to achieve the objectives of the study.
  19. Any other severe or unstable medical condition that, in the opinion of the Investigator or Sponsor, could be expected to progress, recur, or change to such an extent that it could put the subject at special risk, or bias the assessment of the clinical or mental status of the subject to a significant degree.
  20. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed.

Information from the National Library of Medicine

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): NCT04880694


Contacts
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Contact: James Pang, PhD +61 466555916 jpang@grandpharma.cn

Locations
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Belgium
Onze-Lieve-Vrouwziekenhuis Aalst, VZW Not yet recruiting
Aalst, Belgium, Moorselbaan 164, 9300 Aalst
Contact: Nikolaas De Neve, Dr.       Kristel.van.varenbergh@olvz-aalst.be   
Universitair Ziekenhuis Brussel Recruiting
Brussel, Belgium, Laarbeeklaan 101, 1090 Brussel
Contact: Sabine Allard, Prof. Dr.       virgini.vanbuggenhout@uzbrussel.be   
Jan Yperman Ziekenhuis vzw Recruiting
Ieper, Belgium, Briekestraat 12, 8900 Ieper
Contact: Wim Terryn, Dr.       florence.havegheer@yperman.net   
CHU Liège Not yet recruiting
Liège, Belgium, Avenue de l'hôpital 1, 4000
Contact: Benoît MISSET, Prof. Dr.       Axelle.bertrand@chuliege.be   
Sponsors and Collaborators
Grand Medical Pty Ltd.
Trium Clinical Consulting
Investigators
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Principal Investigator: James Pang, PhD Grand Medical Pty Ltd.
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Responsible Party: Grand Medical Pty Ltd.
ClinicalTrials.gov Identifier: NCT04880694    
Other Study ID Numbers: GPHIP-0202
2021-000399-12 ( EudraCT Number )
First Posted: May 11, 2021    Key Record Dates
Last Update Posted: June 14, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Grand Medical Pty Ltd.:
COVID-19
Additional relevant MeSH terms:
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COVID-19
Pneumonia
Virus Diseases
Coronavirus Infections
Respiratory Tract Infections
Infections
Pneumonia, Viral
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases