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

Sponsor

AO GENERIUM (Industry)

Overall Status

Completed

CT.gov ID

NCT04468100

Collaborator

(none)

100

Enrollment

Locations

Arms

8.5

Actual Duration (Months)

7.1

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis Fibrosis	Biological: Tigerase® Biological: Pulmozyme®	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 30, 2017

Actual Primary Completion Date :

May 16, 2018

Actual Study Completion Date :

May 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tigerase® Dornase alfa	Biological: Tigerase® 2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days Other Names: dornase alfa
Active Comparator: Pulmozyme® Dornase alfa	Biological: Pulmozyme® 2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days Other Names: dornase alfa

Arm

Intervention/Treatment

Experimental: Tigerase®

Dornase alfa

Biological: Tigerase®

2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days

Other Names:

dornase alfa

Active Comparator: Pulmozyme®

Dornase alfa

Biological: Pulmozyme®

2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days

Other Names:

dornase alfa

Outcome Measures

Primary Outcome Measures

Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline [FEV1 - forced expiratory volume in the first second of a forced expiratory maneuver by standard spirometry]
Week 24 ± 1

Secondary Outcome Measures

Change in forced lung capacity (FVC) compared to baseline [Week 24 ± 1]
FVC - forced lung capacity by standard spirometry
The number of exacerbations of chronic pulmonary disease [Week 24 ± 1]
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.
The number of days before the chronic pulmonary disease exacerbation development [Week 24 ± 1]
Change in body weight compared to baseline [Week 24 ± 1]
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 [Week 24 ± 1]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed Patient Informed Consent Form for participation in the study;
Men and women 18 years and older;
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;
FEV1 ≥40% and ≤100% of the proper value;
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:

Hypersensitivity to any of used study drug, to their components, as well as a history of significant allergic reactions;
Acute respiratory infection or exacerbation of chronic pulmonary disease within 4 weeks prior to screening and without corticosteroid or antibiotic therapy;
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);

A history of lung transplantation or planned transplantation during this study;
The presence of antibodies to HIV, active viral hepatitis B and / or C and / or cirrhosis in the history or detected on Screening;
Pregnancy and lactation;
Refusal of patients with preserved reproductive potential to use adequate contraception throughout the study and within 30 days after the end of the study;
Patients who underwent a blood or blood components transfusion within 10 days prior to screening;
Drug or alcohol abuse at the time of Screening or in the past;
Patient's participation in any other clinical trials and / or administration of an experimental drug within 30 days prior to the Screening Visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regional Clinical Hospital	Barnaul	Altai Region	Russian Federation	656024
2	Crimean federal university named after V.I.Vernadsky	Simferopol	Crimea Republic	Russian Federation	295007
3	Republican Clinical hospital named after G.G. Kuvatov	Ufa	Republic Of Bashkortostan	Russian Federation	450005
4	Kazan state medical University of Ministry of health, Hospital Therapy Department	Kazan	Republic Of Tatarstan	Russian Federation	420012
5	Sverdlovsk Regional clinical hospital No. 1	Ekaterinburg	Sverdlovsk Region	Russian Federation	620102
6	Chelyabinsk Regional Clinical hospital	Chelyabinsk		Russian Federation	454076
7	City Clinical Hospital named after D.D. Pletnev	Moscow		Russian Federation	105077
8	City Multidisciplinary Hospital No. 2	Saint Petersburg		Russian Federation	194354
9	Regional clinical Hospital	Saratov		Russian Federation	410053
10	Scientific medical center of General Medicine and pharmacologies	Stavropol		Russian Federation	355000
11	Tomsk national medical research Center of the Russian Academy of Sciences, Genetic Clinic Research Institute medical genetics	Tomsk		Russian Federation	634050
12	Volgograd State Medical University, Department of clinical pharmacology and intensive care	Volgograd		Russian Federation	400066
13	Children's Clinical Hospital No. 1 ", Cystic Fibrosis center	Yaroslavl		Russian Federation	150003
14	Clinical hospital No. 2	Yaroslavl		Russian Federation	150010