Inhaled Recombinant Non-immunogenic Staphylokinase vs Placebo in Patients With COVID-19 - FORRIF Trial

COVID-19 Clinical Trial

— FORRIF  

Official title:

Inhaled Recombinant Non-immunogenic Staphylokinase vs Placebo in Patients With COVID-19 - FORRIF Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05135546
• Other study ID #: FORRIF
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: December 27, 2021
• Est. completion date: May 31, 2023

Study information

• Verified date: June 2023
• Source: Supergene, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Objective: to evaluate the tolerability, safety and efficacy of inhaled usage of the Recombinant Non-immunogenic Staphylokinase (Fortelyzin®) vs placebo in patients with COVID-19.

Description:

Fortelyzin® (the active substance Forteplase) is a recombinant non-immunogenic staphylokinase with high fibrinselective thrombolytic activity. In a multicentre, randomised clinical trial in patients with ST-segment elevation myocardial infarction (FRIDOM), non-immunogenic staphylokinase was administered as a single intravenous bolus of 15 mg in all patients, regardless of bodyweight, and showed similar high reperfusion patency and fewer minor bleeding events compared with tenecteplase, as well as the absence of neutralising IgGs. Results of the multicentre, randomised clinical trial in patients with an acute ischaemic stroke (FRIDA) suggested that the non-immunogenic staphylokinase administrated as a single intravenous bolus of 10 mg in all patients within the 4-5 h after the onset of symptoms is non-inferior to alteplase. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ between treatment groups (Gusev EI, Martynov MYu, Nikonov AA et al. Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4-5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial. Lancet Neurol. 2021; 20(9): 721-728).

Complex coagulation and hematologic abnormalities, including significantly elevated D-dimer and fibrin/fibrinogen values are the distinct features identified in severe SARS-CoV-2. In the list of antithrombotic therapy drugs in conjunction with anticoagulant and antiplatelet therapy in patients with COVID-19, published by Liverpool Drug Interactions Group, fibrinolytic therapy is also included.

So the main objectives of this study are to assess the tolerability, safety and efficacy of inhaled usage of fibrinolytic agent the recombinant non-immunogenic staphylokinase (Fortelyzin®) in patients with COVID-19.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: May 31, 2023
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men and women aged 18 and over

• Clinical status according to the WHO scale - 6, 7, 8 and 9 points.

• Verified respiratory infection COVID-19 by real-time PCR (quantitative)

• Patient consent to use reliable contraceptive methods throughout the study and for 3 weeks after:

• women who have a negative pregnancy test and use the following contraceptives:

intrauterine devices, oral contraceptives, contraceptive patch, prolonged injectable contraceptives, double barrier method of contraception. Women who are not fertile can also take part in the study (documented conditions: hysterectomy, tubal ligation, infertility, menopause for more than 1 year);

• men using barrier contraception. The study may also involve men who are not fertile (documented conditions: vasectomy, infertility)

• Availability of signed and dated informed consent of the patient to participate in the study.

Exclusion Criteria:

• Clinical status according to the WHO scale - 1, 2, 3, 4 and 5 points.

• Increased risk of bleeding:

• extensive bleeding at the present time;

• intracranial (including subarachnoid) hemorrhage at the present time.

• Lactation, pregnancy

• Known hypersensitivity to Fortelyzin®.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Recombinant nonimmunogenic staphylokinase
15 mg of drug reconstituted in 6 ml of 0.9% solution of NaCl for inhalation Other Name: Fortelyzin®
• Placebo
6 ml of 0.9% solution of NaCl for inhalation

Locations

Country	Name	City	State
Russian Federation	City Clinical Hospital No.52	Moscow
Russian Federation	N.V. Sklifosovsky Research Institute of Emergency Medicine	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
Supergene, LLC	Russian Academy of Medical Sciences

Country where clinical trial is conducted

Russian Federation, 

References & Publications (1)

Gusev EI, Martynov MY, Nikonov AA, Shamalov NA, Semenov MP, Gerasimets EA, Yarovaya EB, Semenov AM, Archakov AI, Markin SS; FRIDA Study Group. Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4.5 h after — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients discharged from the hospital with clinical status according to the WHO Ordinal Scale For Clinical Improvement - 3 points or less	The efficacy is evaluated in terms of the number of patients discharged from the hospital with clinical status according to the WHO Ordinal Scale For Clinical Improvement - 3 points or less	28 days post randomization
Secondary	Number of patients discharged from the hospital with clinical status according to the WHO Ordinal Scale For Clinical Improvement - 3 points or less	The efficacy is evaluated in terms of the number of patients discharged from the hospital with clinical status according to the WHO Ordinal Scale For Clinical Improvement - 3 points or less	14 days post randomization
Secondary	Hospital length of stay	The efficacy is evaluated in terms of the hospital length of stay	28 days post randomization
Secondary	Number of ICU-free days	The efficacy is evaluated in terms of the number of ICU-free days	28 days post randomization
Secondary	Number of ventilation-free days	The efficacy is evaluated in terms of the number of ventilation-free days	28 days post randomization
Secondary	Number of oxygen support-free days	The efficacy is evaluated in terms of the number of oxygen support-free days	28 days post randomization
Secondary	SpO2 level	The efficacy is evaluated in terms of the SpO2 level	7, 14 and 28 days post randomization