Efficacy and Safety of Elizaria® vs. Soliris® in Patients With PNH

NCT04463056 | Completed Phase 3

• 2 other identifiers: ECU-PNH-III#546 eff date 17.10.2017
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief Summary

It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety of Elizaria® (eculizumab, GENERIUM JSC, Russia) versus Soliris® (Alexion Pharma GmbH, Switzerland) in patients with paroxysmal nocturnal hemoglobinuria.

Conditions

Paroxysmal Nocturnal Hemoglobinuria; Marchiafava-Micheli Syndrome; Paroxysmal Hemoglobinuria

Keywords

Paroxysmal Cold Hemoglobinuria; eculizumab; Complement Inactivating Agents; Hemolysis; Anemia, Hemolytic; Anemia; Hematologic Diseases; Bone Marrow Diseases; Hemoglobinuria; Proteinuria

Outcome Measures

Primary Outcomes (1)

• Area under the LDH concentration-time curve (LDH AUC) during the maintenance therapy with the test drug or the reference drug

  week 22

Secondary Outcomes (7)

• Area under the LDH concentration-time curve (LDH AUC) during 26-week therapy with the test product or the reference product

  week 26

• Hemoglobin level change during the maintenance therapy with the test drug or the reference drug

  week 22

• Number/proportion of the patients with stable hemoglobin level during the maintenance therapy with the test drug or the reference drug

  week 22

• Number/proportion of patients with various thrombotic complications developing during treatment with the test product or the reference product.

  week 26

• Number/proportion of patients who needed donor red blood cell transfusions during treatment with the test product or the reference product.

  week 26

Study Arms (2)

Elizaria®

EXPERIMENTAL

International nonproprietary name: eculizumab

Biological: Elizaria®

Soliris®

ACTIVE COMPARATOR

International nonproprietary name: eculizumab

Biological: Soliris®

Interventions

Elizaria® BIOLOGICAL

Induction cycle: 600 mg (2 vials of 30 mL, 10 mg/mL) intravenous infusion for 30 minutes once a week for 4 weeks. Maintenance therapy: 900 mg (3 vials of 30 mL, 10 mg/mL) intravenous infusion for 30 minutes in Week 5, followed by 900 mg every 14 days.

Also known as: eculizumab

Elizaria®

Soliris® BIOLOGICAL

Induction cycle: 600 mg (2 vials of 30 mL, 10 mg/mL) intravenous infusion for 30 minutes once a week for 4 weeks. Maintenance therapy: 900 mg (3 vials of 30 mL, 10 mg/mL) intravenous infusion for 30 minutes in Week 5, followed by 900 mg every 14 days.

Also known as: eculizumab

Soliris®

Eligibility Criteria

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

You may qualify if:

• Written informed consent for participation in the study.
• Men and women aged 18 to 65 years at the time of signing the Informed Consent Form.
• Established diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), confirmed by flow cytometry assessing the PNH red blood cell and white blood cell clone size, with intravascular hemolysis and current or previous concomitant clinical symptoms, irrespective of the need for blood transfusions and without signs of other disorders associated with bone marrow failure.
• The patients receiving anticoagulants must take them at a stable dose for at least 4 weeks prior to screening. Patients receiving warfarin must have a stable international normalized ratio (INR) value. To confirm INR value stability, the patients have to provide a blood INR test at least 4 weeks prior to screening. The second INR assessment will be performed at the screening visit.
• Documented vaccination against meningococcal infections (Neisseria meningitidis serogroups A, C, Y and W-135) the protective immunity of which did not wear off, at least 14 days prior to the administration of the first dose of the test or reference drug and the patient's consent for revaccination against meningococcal infections (Neisseria meningitidis serogroups A, C, Y and W-135) during participation in the current study if the protection from previous vaccination wears off.
• Subjects' consent to use reliable contraceptive methods (the combination of at least 2 methods, including barrier contraception, for example, condoms with spermicide) from signing the Informed Consent Form for up to 10 weeks after stopping therapy.

You may not qualify if:

• Hypersensitivity to the test drug, reference drug and their components.
• Hypersensitivity to the active substance or any other component of the vaccine used to prevent meningococcal infection or a lifethreatening reaction to a previously administered vaccine containing similar ingredients.
• Conditions associated with bone marrow failure and PNH clone (aplastic anemia, myelodysplastic syndrome, idiopathic myelofibrosis).
• A history of infections caused by Neisseria meningitides.
• Active systemic bacterial, viral, or fungal infection within 14 days prior to the administration of the first dose of the test or reference drug.
• Fever of 38°С or higher within 7 days prior to the administration of the first dose of the test or reference drug.
• Hereditary complement deficiencies.
• Patients planning to undergo or with a history of bone marrow transplantation.
• Vaccination with any live vaccine within 1 month prior to the administration of the first dose of the test or reference drug;
• Concomitant diseases and conditions which may, in the Investigator's opinion, compromise the patient's safety in case of participation in the study or which could affect the safety data analysis in case of an exacerbation of this disease/condition during the study, including the following:
• Myocardial infarction or stroke within the last 3 months, severe arrhythmia, NYHA functional class III/IV heart failure;
• Psychiatric disorders;
• Immune and endocrine disorders which are not controlled with medications (including decompensated diabetes mellitus and thyroid disorders);
• Hematologic disorders requiring chemotherapy;
• Current or prior oncologic disorders, except for successfully treated basal cell carcinoma;

Sponsors & Collaborators

• AO GENERIUM: lead

Study Sites (4)

Federal State Budget Funded Institution National Medical Research Center of Hematology, Ministry of Health of the Russian Federation (MoH of Russia)

Moscow, 125167, Russia

Location

Moscow State Budget Funded Healthcare Institution S. P. Botkin City Clinical Hospital, Moscow Department of Healthcare

Moscow, 125284, Russia

Location

State Budget Funded Institution of Higher Education Academician I. P. Pavlov Saint-Petersburg State Medical University of the Ministry of Health of the Russian Federation

Saint Petersburg, 197022, Russia

Location

State Budgetary Educational Institution of Higher Professional Education Samara State Medical University, Ministry of Health of the Russian Federation.

Samara, 443079, Russia

Location

Related Publications (1)

• Kulagin AD, Ptushkin VV, Lukina EA, Davydkin IL, Korobkin AV, Shamrai VS, Konstantinova TS, Kaporskaya TS, Mitina TA, Ksenzova TI, Zuev EV, Markova OA, Gapchenko EV, Kudlay DA. Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab. Ann Hematol. 2021 Nov;100(11):2689-2698. doi: 10.1007/s00277-021-04624-7. Epub 2021 Aug 16.

  PMID: 34398258 DERIVED

Related Links

• Kulagin, A.D., Ptushkin, V.V., Lukina, E.A. et al. Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab. Ann Hematol (2021). https://doi.org/10.1007/s00277-021-04624-7

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Hemolysis; Anemia, Hemolytic; Anemia; Hematologic Diseases; Bone Marrow Diseases; Hemoglobinuria; Proteinuria

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms

Study Officials

• Oksana A. Markova, MD

  AO GENERIUM

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2020
• First Posted: July 9, 2020
• Study Start: November 29, 2017
• Primary Completion: October 16, 2018
• Study Completion: October 16, 2018
• Last Updated: September 1, 2021

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

RU (4)