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

NCT ID: NCT05135546

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-27
• Study Completion Date: 2023-05-31

Brief 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.

Detailed 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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Experimental

Recombinant nonimmunogenic staphylokinase lyophilisate for preparation of a solution for inhaled administration, 5 mg (745,000 IU) complete with a solvent. 15 mg (2,235,000 IU) - 3 vials, regardless of body weight.

Group Type: EXPERIMENTAL

Recombinant nonimmunogenic staphylokinase

Intervention Type: DRUG

15 mg of drug reconstituted in 6 ml of 0.9% solution of NaCl for inhalation Other Name: Fortelyzin®

Placebo control

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

6 ml of 0.9% solution of NaCl for inhalation

Interventions

Recombinant nonimmunogenic staphylokinase

15 mg of drug reconstituted in 6 ml of 0.9% solution of NaCl for inhalation Other Name: Fortelyzin®

Intervention Type: DRUG

Placebo

6 ml of 0.9% solution of NaCl for inhalation

Intervention Type: DRUG

Other Intervention Names

Saline solution

Eligibility Criteria

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®.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Russian Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Supergene, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergey S. Markin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

LLC "SuperGene"

Locations

City Clinical Hospital No.52

Moscow, , Russia

N.V. Sklifosovsky Research Institute of Emergency Medicine

Moscow, , Russia

Countries

Russia

References

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 symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial. Lancet Neurol. 2021 Sep;20(9):721-728. doi: 10.1016/S1474-4422(21)00210-6.

Reference Type: RESULT

PMID: 34418399 (View on PubMed)

Other Identifiers

FORRIF

Identifier Type: -

Identifier Source: org_study_id