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

Phase 1

Completed

• Conditions: B-cell Lymphomas
• Interventions: Drug: HLX01

• Registration Number: NCT03218072
• Lead Sponsor: Shanghai Henlius Biotech

Brief Summary

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

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 Timeline

• Study Start: 2014-05-04
• Primary Completion: 2015-01-31
• Study Completion: 2015-01-31
• Study First Submitted: 2017-07-07
• Study First Submitted QC: 2017-07-12
• Study First Posted: 2017-07-14
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-04
• Last Update Posted: 2022-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HLX01 375 mg/m2	HLX01	HLX01 375 mg/m2 administrated intravenously
HLX01 250 mg/m2	HLX01	HLX01 250 mg/m2 administrated intravenously
HLX01 500 mg/m2	HLX01	HLX01 500 mg/m2 administrated intravenously

Primary Outcome Measures

Name	Time	Method
AEs	From First infusion to Day 90	The type, severity and incidence of adverse events
SAEs	From First infusion to Day 90	Thetype, severity and incidence of SAEs

Secondary Outcome Measures

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