Paroxysmal Nocturnal HemoglobinuriaNAPNCT04671810
Prospective Observational Study of Long-term Pathogenic Treatment of Elizaria®
An observational study of Paroxysmal Nocturnal Hemoglobinuria, run by AO GENERIUM at 8 sites in Russia.
Trial summary
This is prospective observational study of long-term pathogenic treatment of Elizaria® in patients with paroxysmal nocturnal hemoglobinuria. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- Elizaria®
- How many people
- 44 participants
- Where
- 8 sitesRussia
- Study dates
- 13 Jun 2019to 5 May 2023
- Phase
- Observational
- 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 years and older
- All sexes
- Adult, Older adult
Study population: The population of the study is the patients with an established diagnosis of PNH who have indications for pathogenic treatment and are receiving Elizaria®.
Who may be able to join
- Male and female patients aged 2 years with an established diagnosis of PNH;
- Prescribing Elizaria® as a pathogenetic therapy;
- Signing by the patient of the informed consent form for participation in the study.
Who cannot join
- 1. Intolerance to eculizumab or other components of the drug.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Russia8 sites
State budgetary healthcare institution "Chelyabinsk Regional Clinical Hospital"
Chelyabinsk, Chelyabinsk Oblast, 454076
State Budgetary Institution of Healthcare Irkutsk Order of the "Badge of Honor" Regional Clinical Hospital
Irkutsk, Irkutsk Oblast, 644079
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
Federal State Budgetary Educational Institution of Higher Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation on the basis of the State Budgetary Institution of Health of the Novosibirsk Region "City Clinic
Novosibirsk, Novosibirsk Oblast, 630091
State budgetary institution of health care of the Republic of Karelia "Republican hospital named after V.A. Baranov "
Petrozavodsk, Republic of Karelia, 185019
State budgetary institution of the Rostov region "Rostov Regional Clinical Hospital"
Rostov-on-Don, Rostov Oblast, 344015
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
State Budgetary Healthcare Institution of the Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No. 1"
Yekaterinburg, Sverdlovsk Oblast, 620102
About this study
Official title: Prospective Observational Study of Long-term Pathogenic Treatment of Elizaria® in Patients With Paroxysmal Nocturnal Hemoglobinuria.
This is prospective observational study of long-term pathogenic treatment of Elizaria® in patients with paroxysmal nocturnal hemoglobinuria.
Read the detailed description
Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired, life-threatening, progressive clonal blood disease that is developed as a result of the expansion of one or more clones of hematopoietic stem cells with a somatic PIG A gene mutation. The main pathogenic mechanism of PNH development is a dysregulation of the complement system, in which there are no complement inhibitors CD55 and CD59 that are bounded by the GPI-anchor on the surface of blood cells, or there is a deficiency of them.
Eculizumab is the first drug for the pathogenetic therapy of PNH, a recombinant humanized monoclonal antibody against the C5 component of complement. Binding with high affinity to C5, eculizumab prevents the cleavage of C5 into C5a and C5b, thereby inhibiting the formation of pro-inflammatory cytokines (via C5a) and Membrane attack complex (MAC) (via C5b).
Using of eculizumab in patients with PNH leads to a significant decrease in hemolysis, the incidence of thrombosis and increasing of the quality of life of patients. It increases life expectancy with long-term using of eculizumab.
The drug Eculizumab, developed by JSC "GENERIUM", Russia, is a biological analogue (biosimilar) of the original drug Soliris®.
The population of the study is the patients with an established diagnosis of PNH who have indications for pathogenic treatment and are receiving Elizaria®.
The study duration for each patient will be at least 54 weeks for previously treated patients, and 58 weeks for previously untreated patients, including the Screening period and the observation period.
The study will include the Screening Period and the Observation Period:
- Screening Period - 2 weeks (Days 1 - 14);
- Follow-up is 52 weeks for previously treated patients and 56 weeks for previously untreated patients.
The screening period can be extended until the results of laboratory and instrumental studies are obtained, but no more than 14 days.
During the observation period, for the purpose of routine examination, it is planned to conduct a number of intermediate visits, approximately every 8 weeks (an acceptable interval of 6-10 weeks) between the Screening Visit (Visit 1) and the Study End Visit (Visit 13) in accordance with the plan of the dispensary observation of the patient. Additional visits and examinations may be carried out by the decision of the research physician.
If the patient is previously untreated, the patient undergoes induction therapy with Elizaria® at a dose of 600 mg weekly for 4 weeks with a further transition to maintenance therapy at a dose of 900 mg from the 5th week and then every 2 weeks.
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- Elizaria®
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Elizaria®Biological
Also called Eculizumab
Elizaria® will be prescribed by the Physician according to the actual SMPC.
What is being measured
The primary outcome is the main question the study is designed to answer.
Dynamics of the peripheral blood LDH level during 52 weeks of the maintenance stage of treatment with Elizaria® (between Visits 6 and 13, inclusive).
To assess the dynamics of the peripheral blood LDH level during 52 weeks the area under the LDH level - time curve (AUC) will be calculated. Descriptive statistics will be provided for the values of the LDH level at each visit, as well as for the AUC, indicating the geometric means and coefficient of variation.
Measured: 52-56 weeks
Secondary outcomes (9)
Changes in hemoglobin levels during maintenance therapy with Elizaria® (between Visits 6 and 13 inclusive)
A paired t-test will be used to assess the change in hemoglobin level during the period of maintenance therapy with Elizaria® (between Visits 6 and 13, inclusive). Data on hemoglobin level and its change at each visit will be presented using descriptive statistics methods.
Measured: 52-56 weeks
Number / proportion of patients with a change in the level of hemoglobin in the blood ± 5 g / l and ± 10 g / l. during the period of maintenance therapy with Elizaria® (between Visits 6 and 13 inclusive)
The proportion of patients with a change in blood hemoglobin level of ± 5 g / L and ± 10 g / L will be given during the period of maintenance therapy with Elizaria® (between Visits 6 and 13 inclusive).
Measured: 52-56 weeks
The number / proportion of patients with various thrombotic complications that developed during treatment with Elizaria®.
For frequency indicators (the proportion of patients with various thrombotic complications) the absolute number of patients in the n / N format and the proportion of patients will be given and also calculated 95% confidence interval (CI) for the proportion.
Measured: 52-56 weeks
The number / proportion of patients requiring transfusion of erythrocyte components of donated blood during treatment with Elizaria®.
For frequency indicators (the proportion of patients requiring transfusions of erythrocyte components of donated blood) the absolute number of patients in the n / N format and the proportion of patients will be given and also calculated 95% confidence interval (CI) for the proportion.
Measured: 52-56 weeks
Number/proportion of patients with breakthrough hemolysis while observing an increased LDH, after a previous decrease in the course of treatment.
For frequency indicators (the proportion of patients with breakthrough hemolysis) the absolute number of patients in the n / N format and the proportion of patients will be given. and also calculated 95% confidence interval (CI) for the proportion.
Measured: 52-56 weeks
Change in the size of PNH-clone of granulocytes and erythrocytes at Visits 6 and 13 relative to the initial value at screening.
To assess the dynamics of quantitative indicators (PNH-clone of granulocytes and erythrocytes, laboratory and vital indicators) relative to the initial level, a paired t-test or Wilcoxon's test will be used in case of a significant deviation from the normal distribution. The normal distribution will be tested using the Shapiro-Wilk test.
Measured: 52-56 weeks
Frequency and severity of adverse events (AEs), serious adverse events (SAEs), including those associated with the use of Elizaria®, according to complaints, physical examination, assessment of vital signs, laboratory and instrumental studies, diaries.
Adverse events (AEs) that have developed since the patient signed the informed consent form will be coded using the MedDRA medical dictionary in the latest edition at the stage of database formation, until it is closed. The data on the incidence of AE / SAE during the course of the study will be presented by organ system (SOC) and preferred terms (PT) in terms of the number and proportion of patients who developed this adverse event. A summary of the severity of AEs and their relationship to treatment will be presented for each organ system.
Measured: 52-56 weeks
Changes in vital signs, physical examination results, ECG, and laboratory values at Visit 13 from baseline at screening.
The number and proportion of patients with abnormalities according to complaints, physical examination, assessment of vital signs, laboratory and instrumental studies and patient diaries will be tabulated.
Measured: 52-56 weeks
Number and proportion of patients with antidrug antibodies; titer of antidrug antibodies and their neutralizing activity.
For frequency indicators (the proportion of patients with antidrug antibodies) the absolute number of patients in the n / N format and the proportion of patients will be given and also calculated 95% confidence interval (CI) for the proportion.
Measured: 52-56 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start13 Jun 2019
- Primary completion28 Dec 2022
- Study completion5 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- AO GENERIUM
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oksana Markova, MD, Study chair, AO GENERIUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04671810
- Sponsor's protocol ID
- ECU-PNH-N01
- Acronym
- NAP
- Status last verified
- Sep 2023
- First submitted
- 1 Dec 2020
- Last updated
- 13 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Observational Study of Long-term Pathogenic Treatment of Elizaria® in Patients With Paroxysmal Nocturnal Hemoglobinuria.
- ClinicalTrials.gov ID
- NCT04671810
- Acronym / sponsor ID
- NAP / ECU-PNH-N01
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- AO GENERIUMIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2019 (actual)
- Primary completion
- 28 Dec 2022 (actual)
- Study completion
- 5 May 2023 (actual)
- First posted
- 17 Dec 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.
This is prospective observational study of long-term pathogenic treatment of Elizaria® in patients with paroxysmal nocturnal hemoglobinuria.
Detailed description
Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired, life-threatening, progressive clonal blood disease that is developed as a result of the expansion of one or more clones of hematopoietic stem cells with a somatic PIG A gene mutation. The main pathogenic mechanism of PNH development is a dysregulation of the complement system, in which there are no complement inhibitors CD55 and CD59 that are bounded by the GPI-anchor on the surface of blood cells, or there is a deficiency of them.
Eculizumab is the first drug for the pathogenetic therapy of PNH, a recombinant humanized monoclonal antibody against the C5 component of complement. Binding with high affinity to C5, eculizumab prevents the cleavage of C5 into C5a and C5b, thereby inhibiting the formation of pro-inflammatory cytokines (via C5a) and Membrane attack complex (MAC) (via C5b).
Using of eculizumab in patients with PNH leads to a significant decrease in hemolysis, the incidence of thrombosis and increasing of the quality of life of patients. It increases life expectancy with long-term using of eculizumab.
The drug Eculizumab, developed by JSC "GENERIUM", Russia, is a biological analogue (biosimilar) of the original drug Soliris®.
The population of the study is the patients with an established diagnosis of PNH who have indications for pathogenic treatment and are receiving Elizaria®.
The study duration for each patient will be at least 54 weeks for previously treated patients, and 58 weeks for previously untreated patients, including the Screening period and the observation period.
The study will include the Screening Period and the Observation Period:
- Screening Period - 2 weeks (Days 1 - 14);
- Follow-up is 52 weeks for previously treated patients and 56 weeks for previously untreated patients.
The screening period can be extended until the results of laboratory and instrumental studies are obtained, but no more than 14 days.
During the observation period, for the purpose of routine examination, it is planned to conduct a number of intermediate visits, approximately every 8 weeks (an acceptable interval of 6-10 weeks) between the Screening Visit (Visit 1) and the Study End Visit (Visit 13) in accordance with the plan of the dispensary observation of the patient. Additional visits and examinations may be carried out by the decision of the research physician.
If the patient is previously untreated, the patient undergoes induction therapy with Elizaria® at a dose of 600 mg weekly for 4 weeks with a further transition to maintenance therapy at a dose of 900 mg from the 5th week and then every 2 weeks.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- The population of the study is the patients with an established diagnosis of PNH who have indications for pathogenic treatment and are receiving Elizaria®.
Key inclusion criteria (3 listed)
- Male and female patients aged 2 years with an established diagnosis of PNH;
- Prescribing Elizaria® as a pathogenetic therapy;
- Signing by the patient of the informed consent form for participation in the study.
Key exclusion criteria (1 listed)
- 1. Intolerance to eculizumab or other components of the 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: EculizumabElizaria® will be prescribed by the Physician according to the actual SMPC. | Biological | – |
Primary outcome
Dynamics of the peripheral blood LDH level during 52 weeks of the maintenance stage of treatment with Elizaria® (between Visits 6 and 13, inclusive).
Time frame: 52-56 weeks
To assess the dynamics of the peripheral blood LDH level during 52 weeks the area under the LDH level - time curve (AUC) will be calculated. Descriptive statistics will be provided for the values of the LDH level at each visit, as well as for the AUC, indicating the geometric means and coefficient of variation.
9 secondary outcomes
Changes in hemoglobin levels during maintenance therapy with Elizaria® (between Visits 6 and 13 inclusive)
Time frame: 52-56 weeks
Number / proportion of patients with a change in the level of hemoglobin in the blood ± 5 g / l and ± 10 g / l. during the period of maintenance therapy with Elizaria® (between Visits 6 and 13 inclusive)
Time frame: 52-56 weeks
The number / proportion of patients with various thrombotic complications that developed during treatment with Elizaria®.
Time frame: 52-56 weeks
The number / proportion of patients requiring transfusion of erythrocyte components of donated blood during treatment with Elizaria®.
Time frame: 52-56 weeks
Number/proportion of patients with breakthrough hemolysis while observing an increased LDH, after a previous decrease in the course of treatment.
Time frame: 52-56 weeks
Change in the size of PNH-clone of granulocytes and erythrocytes at Visits 6 and 13 relative to the initial value at screening.
Time frame: 52-56 weeks
Frequency and severity of adverse events (AEs), serious adverse events (SAEs), including those associated with the use of Elizaria®, according to complaints, physical examination, assessment of vital signs, laboratory and instrumental studies, diaries.
Time frame: 52-56 weeks
Changes in vital signs, physical examination results, ECG, and laboratory values at Visit 13 from baseline at screening.
Time frame: 52-56 weeks
Number and proportion of patients with antidrug antibodies; titer of antidrug antibodies and their neutralizing activity.
Time frame: 52-56 weeks
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 13 Sep 2023.
- Individual participant dataSharing planned: No
Related trials for Paroxysmal Nocturnal Hemoglobinuria
Enrolling by invitationObservational study
An Observational Post-Authorization Safety and Effectiveness Study of Ravulizumab in Adult Patients Aged 18 and Older Diagnosed With Paroxysmal Nocturnal Hemoglobinuria Using Multicenter Electronic Medical Records in South Korea
Hemoglobinuria, Paroxysmal
RecruitingPhase 2
Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells
Severe Aplastic Anemia, MDS (Myelodysplastic Syndrome)
RecruitingPhase 3
A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works
Paroxysmal Nocturnal Hemoglobinuria
Not yet recruitingPhase 3
A Study of Efficacy and Safety of FXS6837 in Anti-C5 Treated PNH Patients.
Paroxysmal Nocturnal Hemoglobinuria
RecruitingPhase 2
Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis
Severe Aplastic Anemia (SAA), Hypo-Plastic Myelodysplastic Syndrome (MDS)
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 Markova, MD study chair
AO GENERIUM
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Paroxysmal Nocturnal Hemoglobinuria, run by AO GENERIUM at 8 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 3 inclusion and 1 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 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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.
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?
Dynamics of the peripheral blood LDH level during 52 weeks of the maintenance stage of treatment with Elizaria® (between Visits 6 and 13, inclusive). (time frame: 52-56 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Sep 2023.