Phase 1 Study of BCD-245 in Subjects With Neuroblastoma

Phase 1

Recruiting

• Conditions: Neuroblastoma

• Registration Number: NCT05782959
• Lead Sponsor: Biocad

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.

Study Timeline

• Study Start: 2021-11-29
• Status Verified: 2023-02
• Study First Submitted: 2023-02-16
• Study First Submitted QC: 2023-03-13
• Last Update Submitted: 2023-03-13
• Study First Posted: 2023-03-24
• Last Update Posted: 2023-03-24
• Primary Completion: 2023-06
• Study Completion: 2023-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Proportion of subjects with serious adverse reactions	52 weeks
Proportion of subjects with adverse reactions of grade 3 or higher according to CTCAE 5.0	52 weeks
Proportion of therapy discontinuations due to adverse reactions	up to 4 weeks
Proportion of subjects with adverse reactions	52 weeks

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects with anti-BCD-245 BAbs and NAbs	52 weeks
Area under the plasma concentration versus time curve from time zero to t (AUC 0-t)	up to 4 weeks
Area under the plasma concentration versus time curve from zero to time infinity (AUC 0-∞)	up to 4 weeks
Peak plasma concentration (Cmax)	up to 4 weeks
Time of peak plasma concentration (Tmax)	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
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

Trial Locations

Locations (3)

Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology; 🇷🇺 Moscow, Russian Federation

Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation; 🇷🇺 Moscow, Russian Federation

Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation; 🇷🇺 Saint Petersburg, Russian Federation