Clinical trial NCT04671810: Prospective Observational Study of Long-term Pathogenic Treatment of Elizaria®
Official title: Prospective Observational Study of Long-term Pathogenic Treatment of Elizaria® in Patients With Paroxysmal Nocturnal Hemoglobinuria.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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®.

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Male and female patients aged 2 years with an established diagnosis of PNH;
2. Prescribing Elizaria® as a pathogenetic therapy;
3. Signing by the patient of the informed consent form for participation in the study.

Exclusion Criteria:

1. Intolerance to eculizumab or other components of the drug.

Primary outcomes:
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).
timeFrame: 52-56 weeks
Secondary outcomes:
measure: Changes in hemoglobin levels during maintenance therapy with Elizaria® (between Visits 6 and 13 inclusive)
timeFrame: 52-56 weeks
measure: 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)
timeFrame: 52-56 weeks
measure: The number / proportion of patients with various thrombotic complications that developed during treatment with Elizaria®.
timeFrame: 52-56 weeks
measure: The number / proportion of patients requiring transfusion of erythrocyte components of donated blood during treatment with Elizaria®.
timeFrame: 52-56 weeks
measure: Number/proportion of patients with breakthrough hemolysis while observing an increased LDH, after a previous decrease in the course of treatment.
timeFrame: 52-56 weeks
measure: Change in the size of PNH-clone of granulocytes and erythrocytes at Visits 6 and 13 relative to the initial value at screening.
timeFrame: 52-56 weeks
measure: 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.
timeFrame: 52-56 weeks
measure: Changes in vital signs, physical examination results, ECG, and laboratory values at Visit 13 from baseline at screening.
timeFrame: 52-56 weeks
measure: Number and proportion of patients with antidrug antibodies; titer of antidrug antibodies and their neutralizing activity.
timeFrame: 52-56 weeks
Other outcomes:
Locations:
city: Chelyabinsk
country: Russian Federation
facility: State budgetary healthcare institution "Chelyabinsk Regional Clinical Hospital"
state: Chelyabinsk Region
city: Irkutsk
country: Russian Federation
facility: State Budgetary Institution of Healthcare Irkutsk Order of the "Badge of Honor" Regional Clinical Hospital
state: Irkutsk Region
city: Moscow
country: Russian Federation
facility: State Budgetary Institution of Healthcare of the City of Moscow City Clinical Hospital named after S.P. Botkin of the Moscow Department of Health
state: Moscow Region
city: Novosibirsk
country: Russian Federation
facility: 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
state: Novosibirsk Region
city: Petrozavodsk
country: Russian Federation
facility: State budgetary institution of health care of the Republic of Karelia "Republican hospital named after V.A. Baranov "
state: Republic Of Karelia
city: Rostov-on-Don
country: Russian Federation
facility: State budgetary institution of the Rostov region "Rostov Regional Clinical Hospital"
state: Rostov Region
city: Samara
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation
state: Samara Region
city: Ekaterinburg
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No. 1"
state: Sverdlovsk Region
Study officials:
affiliation: AO GENERIUM
name: Oksana Markova, MD
role: STUDY_CHAIR
References: