Efficacy and Safety of Tigerase® vs. Pulmozyme® in Patients With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04468100
• Other study ID #: DRN-CFR-III
• Secondary ID: 348 eff date 23.
• Status: Completed
• Phase: Phase 3
• Start date: August 30, 2017
• Est. completion date: May 16, 2018

Study information

• Verified date: July 2020
• Source: AO GENERIUM
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 16, 2018
• Est. primary completion date: May 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Biological:
• Tigerase®
2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days
• Pulmozyme®
2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days

Locations

Country	Name	City	State
Russian Federation	Regional Clinical Hospital	Barnaul	Altai Region
Russian Federation	Chelyabinsk Regional Clinical hospital	Chelyabinsk
Russian Federation	Sverdlovsk Regional clinical hospital No. 1	Ekaterinburg	Sverdlovsk Region
Russian Federation	Kazan state medical University of Ministry of health, Hospital Therapy Department	Kazan	Republic Of Tatarstan
Russian Federation	City Clinical Hospital named after D.D. Pletnev	Moscow
Russian Federation	City Multidisciplinary Hospital No. 2	Saint Petersburg
Russian Federation	Regional clinical Hospital	Saratov
Russian Federation	Crimean federal university named after V.I.Vernadsky	Simferopol	Crimea Republic
Russian Federation	Scientific medical center of General Medicine and pharmacologies	Stavropol
Russian Federation	Tomsk national medical research Center of the Russian Academy of Sciences, Genetic Clinic Research Institute medical genetics	Tomsk
Russian Federation	Republican Clinical hospital named after G.G. Kuvatov	Ufa	Republic Of Bashkortostan
Russian Federation	Volgograd State Medical University, Department of clinical pharmacology and intensive care	Volgograd
Russian Federation	Children's Clinical Hospital No. 1 ", Cystic Fibrosis center	Yaroslavl
Russian Federation	Clinical hospital No. 2	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
AO GENERIUM

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline	Week 24 ± 1	FEV1 - forced expiratory volume in the first second of a forced expiratory maneuver by standard spirometry
Secondary	Change in forced lung capacity (FVC) compared to baseline	FVC - forced lung capacity by standard spirometry	Week 24 ± 1
Secondary	The number of exacerbations of chronic pulmonary disease	Clinical symptoms of chronic pulmonary disease exacerbation required antibiotic therapy in CF patients, include the presence of at least 4 of 12 possible signs or symptoms; A change in color or amount of sputum; The appearance or intensification of hemoptysis; Strengthening cough; Increased shortness of breath; Increased malaise, fatigue or lethargy; Temperature above 38 ° C; Anorexia or weight loss; Sinuses pain or soreness; Changes in the nature of sinuses mucus; Changes in chest physical examination; Pulmonary function decrease at list 10% or more; Radiographic changes.	Week 24 ± 1
Secondary	The number of days before the chronic pulmonary disease exacerbation development		Week 24 ± 1
Secondary	Change in body weight compared to baseline		Week 24 ± 1
Secondary	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	St. George's Respiratory Questionnaire (SGRQ), a questionnaire for patients with respiratory diseases is designed to assess the chronic obstructive pulmonary disease patients quality of life.; The questionnaire consists of 76 questions, which are grouped in 3 parts: The first part - symptoms - measures the degree of anxiety caused by respiratory symptoms.; The second part - activity - measures the limitation of mobility and physical activity.; The third part - the influence - evaluates the existing psychosocial consequences of bronchial obstruction.	Week 24 ± 1

External Links

•   Efficacy and safety of the biosimilar medicinal product Tigerase® (dornase alfa) in long-term symptomatic treatment of patients with cystic fibrosis: results of a phase III clinical trial