A Safety and Immunogenicity Study in Long-term Treatment of Eculizumab (JSC "GENERIUM", Russian Federation)

NCT04679103 | Completed Phase 3

• 2 other identifiers: ECU-PNH-III-X№205. eff.data 03 May 2018
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 9

Brief Summary

A safety and immunogenicity study in long-term treatment of Eculizumab (JSC "GENERIUM", Russian Federation) in patients with paroxysmal nocturnal hemoglobinuria, who have been involved earlier in the clinical trials of Eculizumab (JSC "GENERIUM", Russian Federation).

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

eculizumab; humanized monoclonal antibodies; safety; paroxysmal nocturnal hemoglobinuria; rare disease; biosimilar; complement system; C5 component of complement; pro-inflammatory cytokines; Membrane attack complex (MAC); immunogenicity

Outcome Measures

Primary Outcomes (6)

• The frequency and severity of adverse events (AEs), serious adverse events (SAEs), including those associated with the use of the study drug.

  Frequency of AE / SAE will be tabulated with an indication of the number and proportion of patients in each category. Data will be presented cumulatively for all patients, as well as by subgroup. Descriptive statistical methods will be used.

  6 months

• The number and proportion of patients with antidrug antibodies; titer of antidrug antibodies and their neutralizing activity.

  The analysis of immunogenicity parameters will be carried out taking into account the total duration of treatment with eculizumab, including the results of previous studies. The baseline will be the results of the analysis before the first administration of the drug in clinical trials.If there is a sufficient number of data on the titer of antidrug antibodies and their neutralizing activity, they will be presented using descriptive statistics with additional indication of geometric means and coefficients of variation.

  6 months

• Changes in vital signs during the study.

  Safety parameters, which are categorical variables (frequency of detection of abnormalities according to physical and instrumental examination data, the presence of abnormalities according to the results of ECG, Echo-CG and laboratory parameters) will be tabulated with an indication of number and proportion of patients in each category. Data will be presented cumulatively for all patients, as well as by subgroup.

  6 months

• Changes in physical examination during the study.

  Safety parameters, which are categorical variables (frequency of detection of abnormalities according to physical and instrumental examination data, the presence of abnormalities according to the results of ECG, Echo-CG and laboratory parameters) will be tabulated with an indication of number and proportion of patients in each category. Data will be presented cumulatively for all patients, as well as by subgroup.

  6 months

• Changes in ECG during the study.

  Safety parameters, which are categorical variables (frequency of detection of abnormalities according to physical and instrumental examination data, the presence of abnormalities according to the results of ECG, Echo-CG and laboratory parameters) will be tabulated with an indication of number and proportion of patients in each category. Data will be presented cumulatively for all patients, as well as by subgroup.

  6 months

• Changes in Doppler echocardiography during the study.

  Safety parameters, which are categorical variables (frequency of detection of abnormalities according to physical and instrumental examination data, the presence of abnormalities according to the results of ECG, Echo-CG and laboratory parameters) will be tabulated with an indication of number and proportion of patients in each category. Data will be presented cumulatively for all patients, as well as by subgroup.

  6 months

Secondary Outcomes (8)

• Cmin will be carried out during the transition from the original Soliris® to the investigational drug.

  6 months

• The activity of the components of the complement system will be carried out during the transition from the original Soliris® to the investigational drug.

  6 months

• Concentration of membrane attack complex (C5b-9) will be carried out during the transition from the original Soliris® to the investigational drug.

  6 months

• Changes in LDH when switching from the original Soliris® to the investigational drug.

  6 months

• Changes in creatinine when switching from the original Soliris® to the investigational drug.

  6 months

Study Arms (1)

Eculisumab (JSC GENERIUM, Russia)

EXPERIMENTAL

Eculizumab

Biological: Eculizumab (JSC GENERIUM, Russia)

Interventions

Eculizumab (JSC GENERIUM, Russia) BIOLOGICAL

Eculizumab

Eculisumab (JSC GENERIUM, Russia)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completion of participation in previous studies of Eculizumab (JSC "GENERIUM") while maintaining the clinical efficacy of the therapy with eculizumab.
• In case of significant deviations from the protocol during participation in previous studies, the decision on the possibility of patient participation in this study is made on an individual basis in agreement with the company Sponsor.
• Written informed consent to participate in this study.
• Documented vaccination against meningococcal infection (serotypes A, C, Y and W135 Neisseria meningitides) with an unexpired period of validity and consent of the patient to undergo booster vaccination against meningococcal infection (serotypes A, C, Y and W135 Neisseria meningitides) while participating in this research when the previous vaccination expires.
• Consent to use a reliable method of contraception (a combination of at least 2 methods, including 1 barrier method, for example, using a condom and spermicide), from the moment of signing the informed consent until 10 weeks after the last administration of the study drug.

You may not qualify if:

• Hypersensitivity to the study drug, as well as to its components.
• Hypersensitivity to the active ingredients or any other component of the vaccine for the prevention of meningococcal infection, or a life-threatening reaction to the previous administration of a vaccine containing similar components.
• Comorbidities and conditions that, in the opinion of the Investigator, endanger the safety of the patient while participating in the study.
• Pregnancy or breastfeeding.
• Alcohol, drug or drug addiction.

Sponsors & Collaborators

• AO GENERIUM: lead

Study Sites (9)

State budgetary healthcare institution "Chelyabinsk Regional Clinical Hospital"

Chelyabinsk, Chelyabinsk Oblast, 454076, Russia

Location

Federal State Budgetary Institution of Science "Kirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency"

Kirov, Kirov Oblast, 610027, Russia

Location

Federal State Budgetary Educational Institution of Higher Education "First St. Petersburg State Medical University named after Academician I.P. Pavlov"

Saint Petersburg, Leningradskaya Oblast', 197022, Russia

Location

Federal State Budgetary Institution "National Medical Research Center of Hematology" of the Ministry of Health of the Russian Federation

Moscow, Moscow Oblast, 125167, Russia

Location

State Budgetary Institution of Healthcare of the City of Moscow City Clinical Hospital named after S.P. Botkin of the Moscow Department of Health

Moscow, Moscow Oblast, 125284, Russia

Location

State budgetary institution of health care of the Moscow region "Moscow Regional Research Clinical Institute named after M.F. Vladimirsky"

Moscow, Moscow Oblast, 129110, Russia

Location

State budgetary institution of the Rostov region "Rostov Regional Clinical Hospital"

Rostov-on-Don, Rostov Oblast, 344015, Russia

Location

Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation

Samara, Samara Oblast, 443099, Russia

Location

State Budgetary Healthcare Institution of the Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No. 1"

Yekaterinburg, Sverdlovsk Oblast, 620102, Russia

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Rare Diseases

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Oksana Markova, MD

  AO GENERIUM

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: NAP
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Interventional

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 22, 2020
• Study Start: May 3, 2018
• Primary Completion: April 20, 2020
• Study Completion: April 20, 2020
• Last Updated: December 28, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (9)