Clinical trial NCT06987864: An Extension Clinical Study of BCD-148 for the Treatment of Patients With PNH Previously Treated in Clinical Study No. BCD-148-2/NOCTURN
Official title: An Extension Clinical Study of BCD-148 (JSC BIOCAD) for the Treatment of Patients With Paroxysmal Nocturnal Hemoglobinuria Previously Treated in Clinical Study No. BCD-148-2/NOCTURN
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: Paroxysmal nocturnal hemoglobinuria
eculizumab
PNH
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2025-05-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To study the long-term safety and efficacy of BCD-148 in patients with paroxysmal nocturnal hemoglobinuria (PNH), previously treated in clinical study (CS) BCD-148-2/NOCTURN

Detailed description: The clinical study BCD-148-EXT was an extension of a multicenter, randomized, open-label, comparative study of the efficacy and safety of BCD-148 in PNH patients versus SOLIRIS® (BCD-148-2/NOCTURN).

Clinical study BCD-148-EXT is a Phase III study extension conducted after completion of BCD-148 900 mg therapy or SOLIRIS® 900 mg by subjects of clinical study BCD-148-2/NOCTURN.

In the BCD-148-EXT clinical study patients continued BCD-148 maintenance therapy for 105 weeks.

The BCD-148-EXT study consisted of two periods: screening period (not more than 7 days inclusive, i.e. 1 week from signing the patient information sheet and IC form) and the treatment period (Weeks 0 to 105 of the study, inclusive). As part of the treatment period, patients received intravenous infusions of the investigational drug BCD-148 in the maintenance therapy regimen.

Eligibility criteria: Inclusion Criteria:

1. Signed IC form for participation in the study.
2. Indications for pathogenesis-based therapy of PNH with an anti-C5 monoclonal antibody (eculizumab).
3. Consent for revaccination against Neisseria meningitidis .
4. Negative pregnancy test for urine human chorionic gonadotropin (HCG) in women at enrollment in study BCD-148-EXT (the test was not performed in women who have been postmenopausal for at least 2 years, or in surgically sterile subjects) .
5. Willingness of patients and their sexual partners of childbearing potential to use reliable contraceptive measures from signing the IC form throughout the study and for 4 weeks after the last drug dosing in the clinical study. This requirement did not apply to patients who underwent surgical sterilization and women who have been postmenopausal for over 2 years. Reliable methods of contraception included the use by partners of one barrier method in combination with one of the following: spermicides, intrauterine device, oral contraceptives (for female partners of male subjects only, for female study participants - upon agreement with the Sponsor and with justification by the investigator) .
6. The ability of the patient to comply with the Protocol requirements, in the Investigator's opinion.

Exclusion Criteria:

1. Patient withdrawal from clinical study BCD-148-2/NOCTURN until its completion for any reason.
2. Pregnancy or breastfeeding, or planning of pregnancy by a female participant/planning conceiving a child by a male participant during the clinical study.
3. Any conditions that, in the investigator's opinion, could increase the patient's risk associated with participation in the study or could affect the assessment of the study results.
4. Hypersensitivity to BCD-148 components, murine proteins, and other components of the products according to the patient's history; hypersensitivity to any component of the meningococcal vaccine.
5. Known alcohol or drug addiction, or signs of alcohol/drug addiction, which, according to the investigator, were a contraindication for the treatment with the study drug or limited the treatment compliance.

Primary outcomes:
measure: Change in lactate dehydrogenase (LDH) level from baseline estimated at Visit 1/Week 0 prior to drug administration
timeFrame: 105 weeks
Secondary outcomes:
measure: Proportion of patients with thrombotic complications
timeFrame: 105 weeks
measure: Change in the size of the PNH clone (change in the number of circulating red blood cells with the PNH phenotype) from baseline estimated at Visit 1/Week 0 prior to drug administration
timeFrame: 105 weeks
measure: Change in the mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Total Score from baseline as assessed at Visit 1/Week 0 prior to drug administration
timeFrame: 105 weeks
measure: Proportion of patients with adverse reactions (ARs), including those meeting the seriousness criteria
timeFrame: 105 weeks
measure: Proportion of patients with grade 3 or higher adverse reactions (ARs) according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0
timeFrame: 105 weeks
measure: Proportion of patients who prematurely withdrew from the study due to ARs
timeFrame: 105 weeks
measure: Proportion of BAb (binding antibodies) and NAb (neutralizing antibodies)-positive patients
timeFrame: 105 weeks
measure: Eculizumab Ctrough (steady-state eculizumab concentration at the end of the dosing interval, before the next scheduled dose, after multiple intravenous infusions of BCD-148)
timeFrame: 105 weeks
measure: Emin of serum complement hemolytic activity and C5 level (minimum serum complement hemolytic activity and C5 levels after administration of BCD-148)
timeFrame: 105 weeks
measure: Etrough of serum complement hemolytic activity and C5 level (the effect magnitude measured at the end of the dosing interval, before the next scheduled dose, at steady state after multiple intravenous infusions of BCD-148)
timeFrame: 105 weeks
Other outcomes:
Locations:
city: Barnaul
country: Russian Federation
facility: Territorial State Budgetary Healthcare Institution "Territorial Clinical Hospital"
city: Kemerovo
country: Russian Federation
facility: State Autonomous Healthcare Institution "S.V. Belyaev Kuzbass Regional Clinical Hospital"
city: Kirov
country: Russian Federation
facility: Federal State Budgetary Institution of Science "Kirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency"
city: Moscow
country: Russian Federation
facility: Moscow State Budgetary Healthcare Institution "S.P. Botkin Municipal Clinical Hospital of the Moscow Healthcare Department"
city: Rostov-on-Don
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University" of the Ministry of Health of the Russian Federation
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
city: St. Petersburg
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Academician I.P. Pavlov First St. Petersburg State Medical University" of the Ministry of Health of the Russian Federation
city: St. Petersburg
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "I.I. Mechnikov North-Western State Medical University" of the Ministry of Health of the Russian Federation
city: Syktyvkar
country: Russian Federation
facility: State Institution "Komi Republican Cancer Clinic"
city: Ufa
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation
city: Yekaterinburg
country: Russian Federation
facility: State Autonomous Healthcare Institution of the Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No. 1"
Study officials:
References: