Neuroblastoma
Conditions
Brief summary
The aim of the study is to investigate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of BCD-245 after its single and multiple intravenous infusions at escalating doses in subjects with relapsed/refractory neuroblastoma.
Detailed description
The study includes 2 stages: 1) Data collection and safety analysis for the first four subjects 12 years of age and older from Cohort 1 2) Data collection and analysis of safety, pharmacokinetics, pharmacodynamics and immunogenicity in all cohorts (Cohorts 1-4). The design of this Phase I study is based on standard 3 + 3 design approaches. Cohort 1 includes 4 subjects aged 12 years old and older, and 2 subjects aged 3 years old and older. Cohorts 2-4 include 3-6 subjects aged 3 years and older.
Interventions
BIOLOGICALBCD-245
BCD-245 is administered as prolonged intravenous infusions during each cycle
Sponsors
Biocad
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 3 years and older (12 years and older for the first four subjects) at the time of signing the informed consent form * Established diagnosis of neuroblastoma (confirmed by the study site laboratory where the subject will be treated) based on: a) histological examination of the tumor tissue (with or without immunohistochemistry) or b) presence of typical tumor agglomerates in the bone marrow and/or meta-iodobenzylguanidine-accumulating focus (foci) and an increase in the level of catecholamine metabolites in serum and/or urine * Relapsed or refractory neuroblastoma resistant to the anti-relapse therapy adopted at the study site * Satisfactory performance status (\>70 on the Lansky or Karnofsky scale) * Life expectancy \>8 weeks
Exclusion criteria
* Indications for radiation therapy, surgical intervention for the primary disease at screening * Isolated CNS relapse of neuroblastoma * Planned use of any anticancer drugs concomitantly with BCD-245 in this clinical trial * The need for continuous use of anticonvulsants * Clinically significant neurological deficit or grade \>2 peripheral neuropathy (CTCAE 5.0) * The need or probable need for systemic continuous use of glucocorticosteroids or other immunosuppressive drugs * Signs of respiratory distress (dyspnea at rest and oxygen saturation \<94% without oxygen supplementation) * Any severe organ dysfunction (\> CTCAE 5.0 severity grade 2) at screening, except for hematological abnormalities. * Body weight less than 10 kg. * Subject receiving anti-GD2 monoclonal antibody therapy within 6 weeks or less prior to intended study drug infusion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects with adverse reactions of grade 3 or higher according to CTCAE 5.0 | 52 weeks |
| Proportion of subjects with serious adverse reactions | 52 weeks |
| Proportion of subjects with adverse reactions | 52 weeks |
| Proportion of therapy discontinuations due to adverse reactions | up to 4 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration versus time curve from zero to time infinity (AUC 0-∞) | up to 4 weeks | — |
| Half-life (T1/2) | up to 4 weeks | Half-life is the time taken to decrease the plasma concentration of a drug to one-half its original value |
| Volume of distribution (Vd) | up to 4 weeks | — |
| Peak plasma concentration (Cmax) | up to 4 weeks | — |
| Time of peak plasma concentration (Tmax) | up to 4 weeks | — |
| Area under the plasma concentration versus time curve from time zero to t (AUC 0-t) | up to 4 weeks | — |
| Mean steady-state peak plasma concentration (Cmax) | 20 weeks | — |
| Pre-dose trough concentration (Ctrough) | 20 weeks | — |
| Counts of lymphocytes and CD56+CD16+ (cytokine-secreting and cytotoxic) NK cells | 52 weeks | — |
| Whole blood cytolytic activity test | 52 weeks | — |
| Proportion of subjects with anti-BCD-245 BAbs and NAbs | 52 weeks | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | 52 weeks | Includes complete response, very good partial response, partial response |
| Duration of response | 52 weeks | — |
| Overall survival | 52 weeks | — |
| Event-free survival | 52 weeks | — |
| Time to response | 52 weeks | — |
Countries
Russia
Contacts
Primary ContactMaria Morozova
Outcome results
None listed