Phase 1 Study of BCD-245 in Subjects With Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

An Open-Label, Dose-Escalation, Non-comparative Clinical Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BCD-245 (JSC BIOCAD, Russia) Administered Intravenously to Subjects With Neuroblastoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05782959
• Other study ID #: BCD-245-1
• Status: Recruiting
• Phase: Phase 1
• Start date: November 29, 2021
• Est. completion date: June 2023

Study information

• Verified date: February 2023
• Source: Biocad
• Contact: Maria Morozova
• Phone: +7 (495) 992 66 28
• Email: morozovama[@]biocad.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Biological:
• BCD-245
BCD-245 is administered as prolonged intravenous infusions during each cycle

Locations

Country	Name	City	State
Russian Federation	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

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall response rate	Includes complete response, very good partial response, partial response	52 weeks
Other	Duration of response		52 weeks
Other	Time to response		52 weeks
Other	Event-free survival		52 weeks
Other	Overall survival		52 weeks
Primary	Proportion of subjects with adverse reactions		52 weeks
Primary	Proportion of subjects with serious adverse reactions		52 weeks
Primary	Proportion of subjects with adverse reactions of grade 3 or higher according to CTCAE 5.0		52 weeks
Primary	Proportion of therapy discontinuations due to adverse reactions		up to 4 weeks
Secondary	Area under the plasma concentration versus time curve from time zero to t (AUC 0-t)		up to 4 weeks
Secondary	Area under the plasma concentration versus time curve from zero to time infinity (AUC 0-8)		up to 4 weeks
Secondary	Peak plasma concentration (Cmax)		up to 4 weeks
Secondary	Time of peak plasma concentration (Tmax)		up to 4 weeks
Secondary	Half-life (T1/2)	Half-life is the time taken to decrease the plasma concentration of a drug to one-half its original value	up to 4 weeks
Secondary	Volume of distribution (Vd)		up to 4 weeks
Secondary	Mean steady-state peak plasma concentration (Cmax)		20 weeks
Secondary	Pre-dose trough concentration (Ctrough)		20 weeks
Secondary	Counts of lymphocytes and CD56+CD16+ (cytokine-secreting and cytotoxic) NK cells		52 weeks
Secondary	Whole blood cytolytic activity test		52 weeks
Secondary	Proportion of subjects with anti-BCD-245 BAbs and NAbs		52 weeks