Clinical Trial of BCD-148 and Soliris® for the Treatment of Patients With Paroxysmal Nocturnal Hemoglobinuria

NCT04060264 | Completed Phase 3

• 1 other identifier: BCD-148-2
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Outcome Measures

Primary Outcomes (1)

• AUC LDH

  AUC - Area Under Curve of Lactate dehydrogenase

  Weeks 5-27

Secondary Outcomes (13)

• The proportion of patients with thrombotic complications

  week 27, week 52

• The proportion of patients who required red blood cell transfusion

  week 27, week 52

• The proportion of patients with stable Hb level during the maintenance therapy period

  Weeks 5-27

• Mean Hb level over the maintenance therapy period

  Weeks 5-27

• Frequency of breakthrough hemolysis episodes

  week 27, week 52

Study Arms (2)

BCD-148

EXPERIMENTAL

14 participants in BCD-148 group. During the main period (first 27 weeks), test product BCD-148 will be administered as 25- to 45-minute intravenous infusions. After Week 27 BCD-148 900 mg will be administered biweekly as maintenance therapy.

Biological: BCD-148

Soliris

ACTIVE COMPARATOR

14 participants in Soliris group. During the main period (first 27 weeks), Soliris® will be administered as 25- to 45-minute intravenous infusions. After Week 27, patients be switched to BCD-148 900 mg biweekly as maintenance therapy.

Biological: BCD-148; Biological: Soliris

Interventions

BCD-148 BIOLOGICAL

Active substance of BCD-148 is eculizumab - a monoclonal antibody that targets complement protein C5. Cycle 1 (induction therapy): 600 mg of eculizumab QW for the first four weeks; Cycle 2 (maintenance therapy): 900 mg of eculizumab at Week 5 and 900 mg of eculizumab every 14±2 days until Week 27 (inclusive) afterwards (dosing regimen for the main study period). QW - once weekly

BCD-148; Soliris

Soliris BIOLOGICAL

Active substance of Soliris is eculizumab - a monoclonal antibody that targets complement protein C5. Cycle 1 (induction therapy): 600 mg of eculizumab QW for the first four weeks; Cycle 2 (maintenance therapy): 900 mg of eculizumab at Week 5 and 900 mg of eculizumab every 14±2 days until Week 27 (inclusive) afterwards (dosing regimen for the main study period).

Soliris

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• He/she gave written informed consent.
• Male or female ≥18 and ≤65 years of age.
• PNH diagnosis documented by flow cytometry data at screening .
• PNH granulocyte clone size ≥10% (according to flow cytometry performed at screening).
• 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.
• Platelet count ≥30х109/L at screening.
• Absolute count of neutrophil granulocytes ≥0.75х109/L at screening.
• Willingness to undergo vaccination against Neisseria meningitidis during the screening period and at least 14 days before the first administration of an investigational product .
• If immunosuppressive drug products are used, the duration of this therapy should be at least three months by informed consent date.
• 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.
• The patient is able, in the Investigator's opinion, to follow study procedures.

You may not qualify if:

• History of meningococcal infection (either well-documented or according to oral information provided by a patient).
• Other well-documented complement deficiencies (except for those concerning complement component 5).
• History of bone marrow transplantation (either well-documented or according to oral information provided by a patient).
• HIV, hepatitis B, active hepatitis C, and syphilis .
• 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.
• 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 .
• 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.
• Use of eculizumab and/other anti-C5 monoclonal antibodies within three months before informed consent .
• Hypersensitivity to any of BCD-148/Soliris® ingredients, murine proteins and other ingredients of these drug products, and to any of meningococcal vaccine ingredients.
• Documented malignancy, except for cured basal cell carcinoma or cervical carcinoma in situ .
• 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.
• Participation in other clinical studies within 30 days before informed consent and during this study.
• Pregnancy or lactation or planning for pregnancy/paternity during the clinical study.

Sponsors & Collaborators

• Biocad: lead

Study Sites (1)

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

Saint Petersburg, Russia

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Study Officials

• Roman Ivanov, PhD

  JSC BIOCAD

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 19, 2019
• Study Start: April 4, 2019
• Primary Completion: April 27, 2020
• Study Completion: December 30, 2020
• Last Updated: February 12, 2021

Record last verified: 2020-11

Locations

RU (1)