Clinical trial NCT04468100: Efficacy and Safety of Tigerase® vs. Pulmozyme® in Patients With Cystic Fibrosis
Official title: A Multicenter Prospective Randomized Comparative Study of Pharmacokinetics, Clinical Efficacy and Safety of Tigerase® (JSC GENERIUM, Russia) vs. Pulmozyme® (Hoffmann-La Roche, Switzerland) as Part of Complex Therapy in Patients With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Fibrosis
Keywords: Dornase
Cystic Fibrosis
Fibrosis
Lung Diseases
Pancreatic Diseases
Digestive System Diseases
Respiratory Tract Diseases
Pathologic Processes
Genetic Diseases, Inborn
Tigerase®
DNase
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2020-07-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety of Tigerase® compared Pulmozyme® in patients with Cystic Fibrosis

Detailed description: Cystic fibrosis (CF) is a common hereditary disease with an autosomal recessive type of inheritance, characterized by systemic damage to the exocrine glands, mainly the bronchopulmonary and gastrointestinal systems. CF is usually characterized by a severe course and poor prognosis. The severity of the disease and the life expectancy of the patient with CF is determined primarily by the state of the bronchopulmonary system; more than 90% of patients die from lung diseases.

CF Pulmonary damage develops as a result of a gene mutation - cystic fibrosis transmembrane regulator of ion conductivity Na and Cl (CFTR-cystic fibrosis transmembrane regulator). The main function of CFTR is to regulate the transport of sodium and chlorine across the cell membrane and is part of the cAMP-dependent chlorine channel. CFTR-protein dysfunction in the bronchial tree epithelial cells leads to a blockage of the chlorine ions transport and an increase in the sodium ions absorption, and impaired fluid secretion through the epithelial cells apical membrane.

Dornase alpha, a human recombinant deoxyribonuclease 1 (rhDNase, rhDNase) hydrolyzes extracellular DNA (viscous polyanion) that enters the sputum from destroyed neutrophils, thereby reducing the adhesion and viscosity of sputum. In CF patients dornase alpha is used as symptomatic therapy in combination with standard therapy in patients with a forced vital capacity (FVC) index of at least 40% of the proper value.

Eligibility criteria: Inclusion Criteria:

1. Signed Patient Informed Consent Form for participation in the study;
2. Men and women 18 years and older;
3. Diagnosis of cystic fibrosis, defined as the presence of disease symptoms and a positive sweat test and / or detection of 2 mutations of the MVTR gene during genotyping;
4. FEV1 ≥40% and ≤100% of the proper value;
5. The ability to understand the protocol requirements, to give written consent to participate in the study (including the use and transfer of information about the patient's health status related to the study).

Exclusion Criteria:

1. Hypersensitivity to any of used study drug, to their components, as well as a history of significant allergic reactions;
2. Acute respiratory infection or exacerbation of chronic pulmonary disease within 4 weeks prior to screening and without corticosteroid or antibiotic therapy;
3. Concomitant diseases and conditions with potential impact the patients safety, including:

   * Severe renal impairment (serum creatinine more than 1.5 times higher than the upper limit of normal);
   * Severe liver impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) blood serum activity is 2.5 times or more higher than the upper limit of the laboratory norm);
4. A history of lung transplantation or planned transplantation during this study;
5. The presence of antibodies to HIV, active viral hepatitis B and / or C and / or cirrhosis in the history or detected on Screening;
6. Pregnancy and lactation;
7. Refusal of patients with preserved reproductive potential to use adequate contraception throughout the study and within 30 days after the end of the study;
8. Patients who underwent a blood or blood components transfusion within 10 days prior to screening;
9. Drug or alcohol abuse at the time of Screening or in the past;
10. Patient's participation in any other clinical trials and / or administration of an experimental drug within 30 days prior to the Screening Visit.

Primary outcomes:
measure: Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline
timeFrame: FEV1 - forced expiratory volume in the first second of a forced expiratory maneuver by standard spirometry
Secondary outcomes:
measure: Change in forced lung capacity (FVC) compared to baseline
timeFrame: Week 24 ± 1
measure: The number of exacerbations of chronic pulmonary disease
timeFrame: Week 24 ± 1
measure: The number of days before the chronic pulmonary disease exacerbation development
timeFrame: Week 24 ± 1
measure: Change in body weight compared to baseline
timeFrame: Week 24 ± 1
measure: Change in the average score for the "Symptoms", "Activity", "Influence" subscales, as well as the average total score of the St. George's Respiratory Questionnaire (SGRQ), version 2.2
timeFrame: Week 24 ± 1
Other outcomes:
Locations:
city: Barnaul
country: Russian Federation
facility: Regional Clinical Hospital
state: Altai Region
city: Simferopol
country: Russian Federation
facility: Crimean federal university named after V.I.Vernadsky
state: Crimea Republic
city: Ufa
country: Russian Federation
facility: Republican Clinical hospital named after G.G. Kuvatov
state: Republic Of Bashkortostan
city: Kazan
country: Russian Federation
facility: Kazan state medical University of Ministry of health, Hospital Therapy Department
state: Republic Of Tatarstan
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional clinical hospital No. 1
state: Sverdlovsk Region
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical hospital
city: Moscow
country: Russian Federation
facility: City Clinical Hospital named after D.D. Pletnev
city: Saint Petersburg
country: Russian Federation
facility: City Multidisciplinary Hospital No. 2
city: Saratov
country: Russian Federation
facility: Regional clinical Hospital
city: Stavropol
country: Russian Federation
facility: Scientific medical center of General Medicine and pharmacologies
city: Tomsk
country: Russian Federation
facility: Tomsk national medical research Center of the Russian Academy of Sciences, Genetic Clinic Research Institute medical genetics
city: Volgograd
country: Russian Federation
facility: Volgograd State Medical University, Department of clinical pharmacology and intensive care
city: Yaroslavl
country: Russian Federation
facility: Children's Clinical Hospital No. 1 ", Cystic Fibrosis center
city: Yaroslavl
country: Russian Federation
facility: Clinical hospital No. 2
Study officials:
affiliation: AO GENERIUM
name: Oksana A. Markova, MD
role: STUDY_CHAIR
References:
citation: Amelina EL, Krasovsky SA, Akhtyamova-Givirovskaya NE, Kashirskaya NY, Abdulganieva DI, Asherova IK, Zilber IE, Kozyreva LS, Kudelya LM, Ponomareva ND, Revel-Muroz NP, Reutskaya EM, Stepanenko TA, Seitova GN, Ukhanova OP, Magnitskaya OV, Kudlay DA, Markova OA, Gapchenko EV. Comparison of biosimilar Tigerase and Pulmozyme in long-term symptomatic therapy of patients with cystic fibrosis and severe pulmonary impairment (subgroup analysis of a Phase III randomized open-label clinical trial (NCT04468100)). PLoS One. 2021 Dec 23;16(12):e0261410. doi: 10.1371/journal.pone.0261410. eCollection 2021.