A Study to Evaluate Safety, Tolerability, PK and PD of HLX01 in Patients With CD20-positive B-cell Lymphomas

A Phase Ia, Multi-centers, Open-label, Dose-escalation Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HLX01 (a Potential Rituximab Biosimilar) in Patients With CD20-positive B-cell Lymphomas

To evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01 (a potential rituximab biosimilar) in patients with CD20-positive B-cell lymphomas.

Study Overview

• Status: Completed
• Conditions: B-cell Lymphomas
• Intervention / Treatment: Drug: HLX01

Detailed Description

This was a phase Ia, multicenter, open-label, dose-escalation clinical study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics characteristics of HLX01 injection in patients with CD20-positive B-cell lymphomas.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years ≤ aged ≤ 65 years, male or female;
• having histologically confirmed diagnosis of relapsed/refractory CD20-positive B-cell lymphomas which needed consolidation therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status≤1 and life expectancy ≥3 months;
• providing signed and dated informed consents.

Exclusion Criteria:

• Usage of rituximab or other anti-CD20 monoclonal antibody within 2 years before enrollment;
• usage of hematopoietic cytokines within 1 week before enrollment, e.g. granulocyte colony stimulating factor (G-CSF);
• recent major surgery (excluding diagnostic surgery) within the past 8 weeks;
• peripheral nervous system diseases or central nervous system diseases;
• inadequate hematologic function met any of the following at screening: white blood cell count <3.0×109/L, absolute neutrophil count (lobocyte and rhabdocyte) <1.5×109/L, platelet count <100×109/L, hemoglobin <90 g/L, for patients with bone marrow involvement, absolute neutrophil count (lobocyte and rhabdocyte) <1.0×109/L, platelet count <75×109/L, hemoglobin <80 g/L;
• inadequate liver function met any of the following at screening: total bilirubin>1.5×the upper limit of normal range (ULN), ALT or AST>2.0×ULN, alkaline phosphatase (ALP)>3.0×ULN;
• abnormal renal function (serum creatinine>1.5×ULN);
• abnormal thyroid function (TSH< lower limit of normal or > upper limit of normal with clinical significance judged by investigators);
• positive test result(s) for serum HIV antigen or antibody;
• seropositivity of HBsAg, or seropositivity of HBcAb and HBV DNA>ULN; seropositivity of Anti HCV antibody;
• history of herpes zoster and left with sequelae or latent infection;
• other serious disease which may restrict subjects to participate in the trial (such as ongoing active infection, uncontrolled diabetes mellitus, severe cardiac insufficiency or angina pectoris, gastric ulcer, active autoimmune disease, etc.);
• pregnancy or breast feeding female, or not willing to use effective contraceptive measures during the study;
• allergic constitution, or known allergic to components of rituximab or other anti-CD20 monoclonal antibody;
• history of alcoholism or drug abuse; participation in other clinical trials within 3 months before enrollment;
• not suitable for enrollment at investigator's discretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX01 250 mg/m2; HLX01 250 mg/m2 administrated intravenously	Drug: HLX01; a potential rituximab biosimilar
Experimental: HLX01 375 mg/m2; HLX01 375 mg/m2 administrated intravenously	Drug: HLX01; a potential rituximab biosimilar
Experimental: HLX01 500 mg/m2; HLX01 500 mg/m2 administrated intravenously	Drug: HLX01; a potential rituximab biosimilar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs	The type, severity and incidence of adverse events	From First infusion to Day 90
SAEs	Thetype, severity and incidence of SAEs	From First infusion to Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf	Area under the serum concentration-time curve from time 0 extrapolated to infinity	From First administration to Day 90
Cmax	Maximum serum concentration	From First administration to Day 90
t1/2	terminal half-life	From First administration to Day 90
CD19 positive B cells	The count of CD19 positive in peripheral blood	From First administration to Day 90
CD20 positive B cells	The count of CD20 positive in peripheral blood	From First administration to Day 90
Antidrug antibodies of HLX01	The concentration of anti-HLX01 in serum	From First administration to Day 90

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Publications and helpful links

General Publications

• Shi Y, Zhang Q, Han X, Qin Y, Ke X, Su H, Liu L, Fu J, Jin J, Feng J, Hong X, Zhang X, Wu D, Jiang B, Dong X. Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01 (a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma. Chin J Cancer Res. 2021 Jun 30;33(3):405-416. doi: 10.21147/j.issn.1000-9604.2021.03.11.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2014
• Primary Completion (Actual): January 31, 2015
• Study Completion (Actual): January 31, 2015

Study Registration Dates

• First Submitted: July 7, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: HLX01-NHL01