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

Primary Purpose

Cystic Fibrosis, Fibrosis

Status

Completed

Phase

Phase 3

Locations

Russian Federation

Study Type

Interventional

Intervention

Tigerase®

Pulmozyme®

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Dornase, Cystic Fibrosis, Fibrosis, Lung Diseases, Pancreatic Diseases, Digestive System Diseases, Respiratory Tract Diseases, Pathologic Processes, Genetic Diseases, Inborn, Tigerase®, DNase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Regional Clinical Hospital
Crimean federal university named after V.I.Vernadsky
Republican Clinical hospital named after G.G. Kuvatov
Kazan state medical University of Ministry of health, Hospital Therapy Department
Sverdlovsk Regional clinical hospital No. 1
Chelyabinsk Regional Clinical hospital
City Clinical Hospital named after D.D. Pletnev
City Multidisciplinary Hospital No. 2
Regional clinical Hospital
Scientific medical center of General Medicine and pharmacologies
Tomsk national medical research Center of the Russian Academy of Sciences, Genetic Clinic Research Institute medical genetics
Volgograd State Medical University, Department of clinical pharmacology and intensive care
Children's Clinical Hospital No. 1 ", Cystic Fibrosis center
Clinical hospital No. 2

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tigerase®

Pulmozyme®

Arm Description

Dornase alfa

Outcomes

Primary Outcome Measures

Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline

Week 24 ± 1

Secondary Outcome Measures

Change in forced lung capacity (FVC) compared to baseline

FVC - forced lung capacity by standard spirometry

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.

The number of days before the chronic pulmonary disease exacerbation development

Change in body weight compared to baseline

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.

Full Information

NCT ID

NCT04468100

First Posted

July 8, 2020

Last Updated

July 8, 2020

Sponsor

AO GENERIUM

1. Study Identification

Unique Protocol Identification Number

NCT04468100

Brief Title

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

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

August 30, 2017 (Actual)

Primary Completion Date

May 16, 2018 (Actual)

Study Completion Date

May 16, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AO GENERIUM

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tigerase®

Arm Type

Experimental

Arm Description

Dornase alfa

Arm Title

Pulmozyme®

Arm Type

Active Comparator

Arm Description

Dornase alfa

Intervention Type

Biological

Intervention Name(s)

Tigerase®

Other Intervention Name(s)

dornase alfa

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Pulmozyme®

Other Intervention Name(s)

dornase alfa

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline

Description

Week 24 ± 1

Time Frame

FEV1 - forced expiratory volume in the first second of a forced expiratory maneuver by standard spirometry

Secondary Outcome Measure Information:

Title

Change in forced lung capacity (FVC) compared to baseline

Description

FVC - forced lung capacity by standard spirometry

Time Frame

Week 24 ± 1

Title

The number of exacerbations of chronic pulmonary disease

Description

Time Frame

Week 24 ± 1

Title

The number of days before the chronic pulmonary disease exacerbation development

Time Frame

Week 24 ± 1

Title

Change in body weight compared to baseline

Time Frame

Week 24 ± 1

Title

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

Description

Time Frame

Week 24 ± 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Oksana A. Markova, MD

Organizational Affiliation

AO GENERIUM

Official's Role

Study Chair

Facility Information:

Facility Name

Regional Clinical Hospital

City

Barnaul

State/Province

Altai Region

ZIP/Postal Code

656024

Country

Russian Federation

Facility Name

Crimean federal university named after V.I.Vernadsky

City

Simferopol

State/Province

Crimea Republic

ZIP/Postal Code

295007

Country

Russian Federation

Facility Name

Republican Clinical hospital named after G.G. Kuvatov

City

Ufa

State/Province

Republic Of Bashkortostan

ZIP/Postal Code

450005

Country

Russian Federation

Facility Name

Kazan state medical University of Ministry of health, Hospital Therapy Department

City

Kazan

State/Province

Republic Of Tatarstan

ZIP/Postal Code

420012

Country

Russian Federation

Facility Name

Sverdlovsk Regional clinical hospital No. 1

City

Ekaterinburg

State/Province

Sverdlovsk Region

ZIP/Postal Code

620102

Country

Russian Federation

Facility Name

Chelyabinsk Regional Clinical hospital

City

Chelyabinsk

ZIP/Postal Code

454076

Country

Russian Federation

Facility Name

City Clinical Hospital named after D.D. Pletnev

City

Moscow

ZIP/Postal Code

105077

Country

Russian Federation

Facility Name

City Multidisciplinary Hospital No. 2

City

Saint Petersburg

ZIP/Postal Code

194354

Country

Russian Federation

Facility Name

Regional clinical Hospital

City

Saratov

ZIP/Postal Code

410053

Country

Russian Federation

Facility Name

Scientific medical center of General Medicine and pharmacologies

City

Stavropol

ZIP/Postal Code

355000

Country

Russian Federation

Facility Name

Tomsk national medical research Center of the Russian Academy of Sciences, Genetic Clinic Research Institute medical genetics

City

Tomsk

ZIP/Postal Code

634050

Country

Russian Federation

Facility Name

Volgograd State Medical University, Department of clinical pharmacology and intensive care

City

Volgograd

ZIP/Postal Code

400066

Country

Russian Federation

Facility Name

Children's Clinical Hospital No. 1 ", Cystic Fibrosis center

City

Yaroslavl

ZIP/Postal Code

150003

Country

Russian Federation

Facility Name

Clinical hospital No. 2

City

Yaroslavl

ZIP/Postal Code

150010

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34941914

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.

Results Reference

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

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