Paroxysmal Nocturnal HemoglobinuriaPhase 3NCT04060264
Clinical Trial of BCD-148 and Soliris® for the Treatment of Patients With Paroxysmal Nocturnal Hemoglobinuria
A Phase 3 study testing BCD-148 and Soliris in people with Paroxysmal Nocturnal Hemoglobinuria, run by Biocad at 1 site in Russia.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- BCD-148 and Soliris
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteRussia
- Study dates
- 4 Apr 2019to 30 Dec 2020
- Phase
- Phase 3
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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 .
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Russia1 site
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
About this study
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
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
- Being tested
- BCD-148, Soliris
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCD-148Biological
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
SolirisBiological
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: BCD-148; Biological: Soliris |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC LDH
AUC - Area Under Curve of Lactate dehydrogenase
Measured: Weeks 5-27
Secondary outcomes (13)
The proportion of patients with thrombotic complications
Measured: week 27, week 52
The proportion of patients who required red blood cell transfusion
Measured: week 27, week 52
The proportion of patients with stable Hb level during the maintenance therapy period
Measured: Weeks 5-27
Mean Hb level over the maintenance therapy period
Measured: Weeks 5-27
Frequency of breakthrough hemolysis episodes
Measured: week 27, week 52
Changes in LDH level over time
Measured: week 27, week 52
Change in the count of circulating red blood cells with the PNH phenotype RBC
Red blood cells (RBC )
Measured: week 27, week 52
Change in mean FACIT-Fatigue score
FACIT Fatigue Scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued)
Measured: week 27, week 52
Change in mean EORTC QLQ-C30 score
EORTC QLQ-C30 is questionnaire developed to assess the quality of life. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).
QLQ - Quality of Life Questionnaire
Measured: week 27, week 52
The proportion of patients with AE/SAE related to an investigational product, in the Investigator's opinion
AE - adverse event, SAE - serious adverse event
Measured: week 27, week 52
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
Measured: week 27, week 52
The proportion of patients who discontinued early due to AE/SAE related to an investigational product, in the Investigator's opinion, by arm
Measured: week 27, week 52
The proportion of BAb- and NAb-positive patients.
BAb - Binding antibodies, NAb - neutralizing antibodies
Measured: week 27, week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2019
- Study start4 Apr 2019
- Primary completion27 Apr 2020
- Study completion30 Dec 2020
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.
- More trials run by BiocadThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biocad
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Roman Ivanov, PhD, Study chair, JSC BIOCAD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04060264
- Sponsor's protocol ID
- BCD-148-2
- Status last verified
- Nov 2020
- First submitted
- 13 Aug 2019
- Last updated
- 12 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04060264
- Acronym / sponsor ID
- BCD-148-2
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- BiocadIndustry (pharma, biotech, devices)
- Study start
- 4 Apr 2019 (actual)
- Primary completion
- 27 Apr 2020 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 19 Aug 2019 (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 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| BCD-148 | Experimental | Biological: BCD-14814 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. |
| Soliris | Active comparator | Biological: BCD-148, Biological: Soliris14 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
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 |
|---|---|---|
| BCD-148Active 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 | Biological | BCD-148, Soliris |
| SolirisActive 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). | Biological | Soliris |
Primary outcome
AUC LDH
Time frame: Weeks 5-27
AUC - Area Under Curve of Lactate dehydrogenase
13 secondary outcomes
The proportion of patients with thrombotic complications
Time frame: week 27, week 52
The proportion of patients who required red blood cell transfusion
Time frame: week 27, week 52
The proportion of patients with stable Hb level during the maintenance therapy period
Time frame: Weeks 5-27
Mean Hb level over the maintenance therapy period
Time frame: Weeks 5-27
Frequency of breakthrough hemolysis episodes
Time frame: week 27, week 52
Changes in LDH level over time
Time frame: week 27, week 52
Change in the count of circulating red blood cells with the PNH phenotype RBC
Time frame: week 27, week 52
Change in mean FACIT-Fatigue score
Time frame: week 27, week 52
Change in mean EORTC QLQ-C30 score
Time frame: week 27, week 52
The proportion of patients with AE/SAE related to an investigational product, in the Investigator's opinion
Time frame: week 27, week 52
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
Time frame: week 27, week 52
The proportion of patients who discontinued early due to AE/SAE related to an investigational product, in the Investigator's opinion, by arm
Time frame: week 27, week 52
The proportion of BAb- and NAb-positive patients.
Time frame: week 27, week 52
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 12 Feb 2021.
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.
Roman Ivanov, PhD study chair
JSC BIOCAD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BCD-148 and Soliris in people with Paroxysmal Nocturnal Hemoglobinuria, run by Biocad at 1 site 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 11 inclusion and 13 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 12 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
AUC LDH (time frame: Weeks 5-27). 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 12 Feb 2021.