Study to AntagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19

NCT04634799 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: STU00213262
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized double blind placebo controlled trial to evaluate the efficacy and safety of novel PAI-1 inhibitor (TM5614) for high-risk patients hospitalized with severe COVID-19 at Northwestern Memorial Hospital. The patients will be randomized in a 1:1 ratio to receive standard of care plus TM5614 or standard of care plus placebo.

Conditions

Covid19

Keywords

PAI-1; TM5614; Plasminogen Activator Inhibitor

Outcome Measures

Primary Outcomes (1)

• Clinical improvement

  Change of at least 2 points in the NIAID-defined ordinal scale (higher scores indicate improved outcome),: 1. Death 2. Hospitalized, receiving invasive mechanical ventilation or ECMO 3. Hospitalized, receiving noninvasive ventilation or high-flow oxygen devices 4. Hospitalized, requiring low-flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to Covid-19) 6. Hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol) 7. Not hospitalized

  7 Days

Secondary Outcomes (3)

• Sequential organ failure assessment (SOFA) score change

  7 Days

• PAI-1 Levels

  48 hours

• Ventilator free days

  14 days

Study Arms (2)

TM5614

ACTIVE COMPARATOR

TM5614 30 mg tablets. 6 tablets (180 mg) taken by mouth, once daily for up to 7 days

Drug: TM5614

Placebo

PLACEBO COMPARATOR

Placebo tablets. 6 tablets taken by mouth, once daily for up to 7 days

Other: Placebo

Interventions

TM5614 DRUG

TM5614 is provided in 30 mg tablets and 6 tablets (180 mg) will be taken in the evening for up to 7 days.

Also known as: Plasminogen activator inhibitor-1 (PAI-1)

TM5614

Placebo OTHER

Matching placebo will be provided and participants will take 6 tablets in the evening for up to 7 days.

Also known as: TM5614 Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Adults ≥65 years old or \< 65 years old AND at least one major cardiometabolic comorbidity (diabetes, hypertension, or cardiovascular disease)
• Established diagnosis of COVID-19 as evidenced by a positive nasopharyngeal or bronchoalveolar lavage viral PCR for SARS-CoV2
• Requiring supplemental oxygen

You may not qualify if:

• Age \<18 years old
• Pregnancy or breast-feeding
• Known contraindication to tissue plasminogen activator (tPA), including
• Active internal bleeding
• History of cerebrovascular accident
• Recent intracranial or intraspinal surgery or trauma
• Intracranial neoplasm, arteriovenous malformation or aneurysm
• Known bleeding diathesis
• Severe uncontrolled hypertension (SBP\>200 persistently \>12 hours)
• Currently receiving therapeutic dose anticoagulation (specifically will exclude those with potential drug-drug interaction such as heparin, apixaban, warfarin)
• Platelets \<50,000
• Hematocrit \<30%
• Not hemodynamically stable in the preceding 4 hours (symptomatic hypotension or systolic BP \<95 mmHg at 2 out of 3 measurements)
• Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary care physician could interfere with the conduct of the study including outcome assessment
• Other patient characteristics (not thought to be related to COVID-19) that portend a very poor prognosis (e.g., severe liver failure, metastatic malignancy)

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (4)

• Chang D, Lin M, Wei L, Xie L, Zhu G, Dela Cruz CS, Sharma L. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA. 2020 Mar 17;323(11):1092-1093. doi: 10.1001/jama.2020.1623.

  PMID: 32031568 BACKGROUND

• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

  PMID: 32007143 BACKGROUND

• Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

  PMID: 32109013 BACKGROUND

• Liu YC, Liao CH, Chang CF, Chou CC, Lin YR. A Locally Transmitted Case of SARS-CoV-2 Infection in Taiwan. N Engl J Med. 2020 Mar 12;382(11):1070-1072. doi: 10.1056/NEJMc2001573. Epub 2020 Feb 12. No abstract available.

  PMID: 32050059 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Plasminogen Activator Inhibitor 1

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

Intervention Hierarchy (Ancestors)

Plasminogen Inactivators; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Blood Proteins; Proteins; Biological Factors

Study Officials

• Sanjiv Shah, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-blind, randomized (1:1)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research, Bluhm Cardiovascular Institute

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 18, 2020
• Study Start: January 8, 2021
• Primary Completion: April 23, 2025
• Study Completion: May 30, 2025
• Last Updated: March 3, 2025

Record last verified: 2025-02

Locations

US (1)