Clinical trial NCT04060264: Clinical Trial of BCD-148 and Soliris® for the Treatment of Patients With Paroxysmal Nocturnal Hemoglobinuria
Official title: Randomized, Open-Label, International, Multi-center, Comparative Study of Efficacy and Safety of BCD-148 (JSC BIOCAD, Russia) and Soliris® in Patients With Paroxysmal Nocturnal Hemoglobinuria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2019-08-19
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: During the main period (first 27 weeks), test product BCD-148 and reference product Soliris®.

After Week 27, patients of both study arms will be switched to BCD-148 900 mg biweekly as maintenance therapy. Duration of this maintenance therapy will be 25 weeks.
Primary purpose: TREATMENT

Brief summary: This clinical study is a randomized, open-label, international, multi-center, comparative study of efficacy and safety of BCD-148 and Soliris® in PNH patients.

It is planned to investigate the efficacy, safety, and immunogenicity of one-year eculizumab course in this study.

PNH - Paroxysmal nocturnal hemoglobinuria


Eligibility criteria: Inclusion Criteria:

1. He/she gave written informed consent.
2. Male or female ≥18 and ≤65 years of age.
3. PNH diagnosis documented by flow cytometry data at screening .
4. PNH granulocyte clone size ≥10% (according to flow cytometry performed at screening).
5. Lactate dehydrogenase (LDH) level ≥1.5 times the upper limit of normal (ULN) at screening and at least one of the following symptoms/syndromes: hemoglobinuria, thrombotic complications, transfusion-dependent chronic hemolysis, anemic syndrome, acute kidney injury episodes or chronic kidney disease, pulmonary hypertension, and signs of smooth muscle dystonia (e.g., abdominal pain, dysphagia, erectile dysfunction, and etc.) within three months before informed consent.
6. Platelet count ≥30х109/L at screening.
7. Absolute count of neutrophil granulocytes ≥0.75х109/L at screening.
8. Willingness to undergo vaccination against Neisseria meningitidis during the screening period and at least 14 days before the first administration of an investigational product .
9. If immunosuppressive drug products are used, the duration of this therapy should be at least three months by informed consent date.
10. The willingness of patients and their sexual partners of childbearing potential to use reliable contraception methods starting from the informed consent, throughout the study, and for four weeks after the last dose of an investigational product. This requirement does not apply to patients who underwent surgical sterilization and women with menopause established more than two years ago. Reliable contraception methods include one barrier method in combination with one of the following: spermicides or an intrauterine device.
11. The patient is able, in the Investigator's opinion, to follow study procedures.

Exclusion Criteria:

1. History of meningococcal infection (either well-documented or according to oral information provided by a patient).
2. Other well-documented complement deficiencies (except for those concerning complement component 5).
3. History of bone marrow transplantation (either well-documented or according to oral information provided by a patient).
4. HIV, hepatitis B, active hepatitis C, and syphilis .
5. A patient with newly diagnosed or relapsing aplastic anemia and/or progressive bone marrow failure with indications for allogeneic bone marrow transplantation or combined immunosuppressive therapy within 6 months after informed consent.
6. Acute infection (either well-documented and/or according to oral information provided by a patient) within 4 weeks before informed consent and/or during the screening period and/or relapse of chronic disease at the moment of informed consent and/or during the screening period .
7. Any other chronic diseases present at the time of the informed consent which can negatively affect the patient's safety during the study, in the Investigator' opinion.
8. Use of eculizumab and/other anti-C5 monoclonal antibodies within three months before informed consent .
9. Hypersensitivity to any of BCD-148/Soliris® ingredients, murine proteins and other ingredients of these drug products, and to any of meningococcal vaccine ingredients.
10. Documented malignancy, except for cured basal cell carcinoma or cervical carcinoma in situ .
11. A known alcoholic or drug abuse or signs of present alcoholic/drug abuse that, in the Investigator's opinion, can be a contraindication to treatment with an investigational product or limit treatment compliance.
12. Participation in other clinical studies within 30 days before informed consent and during this study.
13. Pregnancy or lactation or planning for pregnancy/paternity during the clinical study.

Primary outcomes:
measure: AUC LDH
timeFrame: Weeks 5-27
Secondary outcomes:
measure: The proportion of patients with thrombotic complications
timeFrame: week 27, week 52
measure: The proportion of patients who required red blood cell transfusion
timeFrame: week 27, week 52
measure: The proportion of patients with stable Hb level during the maintenance therapy period
timeFrame: Weeks 5-27
measure: Mean Hb level over the maintenance therapy period
timeFrame: Weeks 5-27
measure: Frequency of breakthrough hemolysis episodes
timeFrame: week 27, week 52
measure: Changes in LDH level over time
timeFrame: week 27, week 52
measure: Change in the count of circulating red blood cells with the PNH phenotype RBC
timeFrame: week 27, week 52
measure: Change in mean FACIT-Fatigue score
timeFrame: week 27, week 52
measure: Change in mean EORTC QLQ-C30 score
timeFrame: week 27, week 52
measure: The proportion of patients with AE/SAE related to an investigational product, in the Investigator's opinion
timeFrame: week 27, week 52
measure: The proportion of patients with СТСАЕ v.5.0 Grade 3-4 AE related to an investigational product, in the Investigator's opinion, by arm
timeFrame: week 27, week 52
measure: The proportion of patients who discontinued early due to AE/SAE related to an investigational product, in the Investigator's opinion, by arm
timeFrame: week 27, week 52
measure: The proportion of BAb- and NAb-positive patients.
timeFrame: week 27, week 52
Other outcomes:
Locations:
city: Saint 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 Healthcare of Russian Federation
Study officials:
affiliation: JSC BIOCAD
name: Roman Ivanov, PhD
role: STUDY_CHAIR
References: