Paroxysmal Nocturnal HemoglobinuriaPhase 3NCT04463056
Efficacy and Safety of Elizaria® vs. Soliris® in Patients With PNH
A Phase 3 study testing Elizaria® and Soliris® in people with Paroxysmal Nocturnal Hemoglobinuria and Marchiafava-Micheli Syndrome, run by AO GENERIUM at 4 sites in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria, Marchiafava-Micheli Syndrome, Paroxysmal Hemoglobinuria
- What is being tested?
- Elizaria® and Soliris®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 4 sitesRussia
- Study dates
- 29 Nov 2017to 16 Oct 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- For patients, who have not received Soliris® before inclusion in this study: lactate dehydrogenase (LDH) level 1.5 times the upper limit of normal or higher as assessed by the central laboratory.
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- Hereditary complement deficiencies.
- Patients planning to undergo or with a history of bone marrow transplantation.
- Initial treatment cycle (induction phase) of Soliris®; completed treatment with Soliris® less than 70 days before study inclusion, not related to the current study participation.
- 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;
- Decompensated liver diseases.
- Acquired immunodeficiency syndrome or human immunodeficiency virus (HIV) infection confirmed by test results.
- Active viral hepatitis B and/or C at screening with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels 5 times the upper limit of normal or higher.
- Positive syphilis test results.
- Body mass index (BMI) ≤17 kg/m2 or ≥30 kg/m2.
- Pregnancy or breastfeeding.
- History of tuberculosis, alcohol addiction, medication abuse, or drug addiction.
- Patient's participation in any clinical studies and/or using of not approved medications in the Russian federation within 30 days before screening.
Trial locations and contacts
4 sites in 1 country.
Russia4 sites
Federal State Budget Funded Institution National Medical Research Center of Hematology, Ministry of Health of the Russian Federation (MoH of Russia)
Moscow, 125167
Moscow State Budget Funded Healthcare Institution S. P. Botkin City Clinical Hospital, Moscow Department of Healthcare
Moscow, 125284
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
State Budgetary Educational Institution of Higher Professional Education Samara State Medical University, Ministry of Health of the Russian Federation.
Samara, 443079
About this study
Official title: A Multicenter, Open Label, Randomized, Parallel-group Study of Efficacy and Safety of Eculizumab (JSC GENERIUM, Russia) vs. Soliris® (Alexion Pharma GmbH, Switzerland) in Patients With Paroxysmal Nocturnal Hemoglobinuria
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.
Read the detailed description
After screening, patients meeting all of the inclusion / non-inclusion criteria and vaccinated against meningococcal infections were divided into two subgroups according to the eculizumab treatment status (Soliris® naïve patients / patients who had received Soliris® at a maintenance dose prior to the trial inclusion). Each subgroup included an even number of patients to maintain recruitment balance. Then, patients of each subgroup were distributed into one of two treatment groups by the method of stratified block randomization at a 1:1 ratio into groups A and B, respectively. In the first group (Group A), patients received infusions of Elizaria (eculizumab, GENERIUM JSC), in the second one (Group B) - infusions of Soliris®.
The duration of participation of each patient in the study, including the screening period, was about 30 weeks.
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria, Marchiafava-Micheli Syndrome, Paroxysmal Hemoglobinuria
- Being tested
- Elizaria®, Soliris®
- Keywords
- Paroxysmal Cold Hemoglobinuria, eculizumab, Complement Inactivating Agents, Hemolysis, Anemia, Hemolytic, Anemia, Hematologic Diseases, Bone Marrow Diseases, Hemoglobinuria, Proteinuria
- Medical subject headings
- Hemoglobinuria, Paroxysmal, Hemolysis, Anemia, Hemolytic, Anemia, Hematologic Diseases, Bone Marrow Diseases, Hemoglobinuria, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Elizaria®Biological
Also called eculizumab
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.
Soliris®Biological
Also called eculizumab
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.
| Study group | Role | What they receive |
|---|---|---|
| Elizaria® | Experimental | International nonproprietary name: eculizumab Receives: Biological: Elizaria® |
| Soliris® | Active comparator | International nonproprietary name: eculizumab Receives: Biological: Soliris® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the LDH concentration-time curve (LDH AUC) during the maintenance therapy with the test drug or the reference drug
Measured: 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
Measured: week 26
Hemoglobin level change during the maintenance therapy with the test drug or the reference drug
Measured: week 22
Number/proportion of the patients with stable hemoglobin level during the maintenance therapy with the test drug or the reference drug
Measured: week 22
Number/proportion of patients with various thrombotic complications developing during treatment with the test product or the reference product.
Measured: week 26
Number/proportion of patients who needed donor red blood cell transfusions during treatment with the test product or the reference product.
Measured: week 26
Number of donor red blood cell transfusions during treatment with the test product or the reference product.
Measured: week 26
Number/proportion of patients with breakthrough hemolysis
Breakthrough hemolysis defined as at least one new episode or worsening of at least one previous signs of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, dyspnea, severe vascular complications (including thrombosis), dysphagia or erectile dysfunction) associated with increased LDH after a previous decrease during treatment.
Measured: week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start29 Nov 2017
- Primary completion16 Oct 2018
- Study completion16 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- AO GENERIUM
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oksana A. Markova, MD, Study chair, AO GENERIUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04463056
- Sponsor's protocol ID
- ECU-PNH-III
- Other IDs
- #546 eff date 17.10.2017
- Status last verified
- Oct 2018
- First submitted
- 3 Jul 2020
- Last updated
- 1 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34398258
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open Label, Randomized, Parallel-group Study of Efficacy and Safety of Eculizumab (JSC GENERIUM, Russia) vs. Soliris® (Alexion Pharma GmbH, Switzerland) in Patients With Paroxysmal Nocturnal Hemoglobinuria
- ClinicalTrials.gov ID
- NCT04463056
- Acronym / sponsor ID
- ECU-PNH-III
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- AO GENERIUMIndustry (pharma, biotech, devices)
- Study start
- 29 Nov 2017 (actual)
- Primary completion
- 16 Oct 2018 (actual)
- Study completion
- 16 Oct 2018 (actual)
- First posted
- 9 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
After screening, patients meeting all of the inclusion / non-inclusion criteria and vaccinated against meningococcal infections were divided into two subgroups according to the eculizumab treatment status (Soliris® naïve patients / patients who had received Soliris® at a maintenance dose prior to the trial inclusion). Each subgroup included an even number of patients to maintain recruitment balance. Then, patients of each subgroup were distributed into one of two treatment groups by the method of stratified block randomization at a 1:1 ratio into groups A and B, respectively. In the first group (Group A), patients received infusions of Elizaria (eculizumab, GENERIUM JSC), in the second one (Group B) - infusions of Soliris®.
The duration of participation of each patient in the study, including the screening period, was about 30 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Elizaria® | Experimental | Biological: Elizaria®International nonproprietary name: eculizumab |
| Soliris® | Active comparator | Biological: Soliris®International nonproprietary name: eculizumab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
- For patients, who have not received Soliris® before inclusion in this study: lactate dehydrogenase (LDH) level 1.5 times the upper limit of normal or higher as assessed by the central laboratory.
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Elizaria®Also: eculizumabInduction 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. | Biological | Elizaria® |
| Soliris®Also: eculizumabInduction 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. | Biological | Soliris® |
Primary outcome
Area under the LDH concentration-time curve (LDH AUC) during the maintenance therapy with the test drug or the reference drug
Time frame: week 22
7 secondary outcomes
Area under the LDH concentration-time curve (LDH AUC) during 26-week therapy with the test product or the reference product
Time frame: week 26
Hemoglobin level change during the maintenance therapy with the test drug or the reference drug
Time frame: week 22
Number/proportion of the patients with stable hemoglobin level during the maintenance therapy with the test drug or the reference drug
Time frame: week 22
Number/proportion of patients with various thrombotic complications developing during treatment with the test product or the reference product.
Time frame: week 26
Number/proportion of patients who needed donor red blood cell transfusions during treatment with the test product or the reference product.
Time frame: week 26
Number of donor red blood cell transfusions during treatment with the test product or the reference product.
Time frame: week 26
Number/proportion of patients with breakthrough hemolysis
Time frame: week 26
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2021.
- Derived from this study: PubMed 34398258Kulagin 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.
- Phase III Clinical Trial of Elizaria® and Soliris® in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria: Results of Comparative Analysis of Efficacy, Safety, and Pharmacological DataLink provided by the sponsor.
- 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/s00277-021-04624-7Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oksana A. Markova, MD study chair
AO GENERIUM
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Elizaria® and Soliris® in people with Paroxysmal Nocturnal Hemoglobinuria and Marchiafava-Micheli Syndrome, run by AO GENERIUM at 4 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the LDH concentration-time curve (LDH AUC) during the maintenance therapy with the test drug or the reference drug (time frame: week 22). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04463056, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2021.