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出境医 / 临床实验 / Pharmacokinetics, Efficacy and Safety of the 304 Injection

Pharmacokinetics, Efficacy and Safety of the 304 Injection

Study Description
Brief Summary:
The purpose of this study is to evaluate the pharmacokinetic of the experimental drug 304 injection compared with rituximab injection in patients with CD20 positive B-cell non-Hodgkin lymphoma who had previously achieved CR/CRu status but had not deteriorated or relapsed. While to assess the safety and efficacy of the experimental drug 304 injection compared with rituximab injection.

Condition or disease Intervention/treatment Phase
CD20 Positive B Cell NHL Drug: 304 injection Drug: rituximab injection Phase 1

Detailed Description:
This is a multi-center, randomized, double-blind, parallel controlled, single-dose study to evaluate the pharmacokinetic, safety and efficacy of 304 injection compared with rituximab injection. To avoid the impact of tumor burden on pharmacokinetics, this study will be conducted in CD20 positive B-cell non-Hodgkin lymphoma patients who have achieved CR/CRu status and have not yet deteriorated or relapsed. All patients will be randomly averagely entered into the experimental group and the control group.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Study of Pharmacokinetics, Efficacy, and Safety of 304 Injection Compared With Rituximab in B Cell Non-Hodgkin's Lymphoma
Actual Study Start Date : December 18, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : October 31, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: experimental group
304 injection.WILL be administered single dose IV in the patients with CD20 positive B cell NHL
Drug: 304 injection
Monoclonal antibodies, 100mg/10ml per injection

Active Comparator: control group
Rituximab will be administered single dose IV in the patients with CD20 positive B cell NHL.
Drug: rituximab injection
100mg/10ml per injection ,manufactured by Roche

Outcome Measures
Primary Outcome Measures :
  1. AUC [0-t] [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab: Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC [0-t])

  2. AUC [0-∞] [ Time Frame: For 85 days ]

    To assess PK parameter of plasma 304 or rituximab:

    Area under the concentration-time curve from time zero extrapolated to infinity (AUC [0-∞])


  3. Cmax [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Observed maximum plasma concentration (Cmax)


Secondary Outcome Measures :
  1. tmax [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Time to Cmax (tmax)

  2. t1/2 [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Elimination half-life (t1/2)

  3. MRT [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Mean residence time (MRT)

  4. Vz [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Apparent volume of distribution(Vz)

  5. CLz [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:apparent clearance (CLz)

  6. ADA [ Time Frame: Up to 9 months ]
    To evaluate the incidence of anti-304 and anti-rituximab antibodies

  7. Adverse events [ Time Frame: Up to 85 days ]
    To evaluate the adverse events (incidence, severity, outcome, causality with the investigational drug, etc.).


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological examination confirmed CD20-positive B-cell non-Hodgkin's lymphoma patients (according to WHO 2008 lymphoid tissue tumor type, and a corresponding medical history basis);
  • Previous treatments with CR/CRu (see Appendix 1 for lymphoma efficacy criteria) and those with CD20-positive B-cell non-Hodgkin's lymphoma who have not yet worsened and relapsed believe that they can benefit from anti-CD20 monoclonal antibody therapy. The diagnosis of CRu requires complete raw data (using CT findings. The preferred enhanced CT examination)
  • At the time of enrollment, the Eastern Oncology Cooperative Group (ECOG) had a physical status score of ≤1 (see Appendix 2 for the evaluation criteria for the ECOG physical status score) and the expected survival period was more than four months
  • In the screening test, WBC≥3×109/L, HGB≥80g/L, ANC≥1.5×109/L, PLT≥75×109/L, left ventricular ejection fraction (LVEF) ) ≥ 50%
  • Female patients of childbearing age were negative for the blood pregnancy test during the screening period. Patients of childbearing age are willing to contraception after signing the informed consent form until 6 months after the end of the study treatment, including but not limited to: hormonal contraception, or physical contraception, or abstinence
  • Be able to understand and comply with clinical trial protocol requirements and voluntarily sign written informed consent

Exclusion Criteria:

  • In the past 5 years, there have been other medical history of malignant tumors (except for local malignant tumors that have been cured, such as cutaneous basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or breast carcinoma in situ)
  • Those who have used chemotherapy drugs within 4 weeks before enrollment
  • The clinical half-life of more than 5 drugs after taking other clinical trials in three months or other clinical trials (whichever is longer)
  • The last time you used rituximab or other anti-CD20 mAbs for no more than 4 months
  • In the screening test, the liver and kidney function tests have any of the following abnormalities: total bilirubin > 1.5 times the upper limit of normal, ALT > 2.5 times the upper limit of normal, AST > 2.5 times the upper limit of normal, ALP > 2.5 times the upper limit of normal, Blood Cr>1.5 times the upper limit of normal value
  • Hyperthyroidism
  • He was transfused within 2 weeks before enrollment, or hematopoietic cytokine therapy, such as granulocyte colony-stimulating factor (G-CSF), thrombopoietin, erythropoietin, etc.
  • Those who were vaccinated or planned to vaccinate (attenuate) live virus vaccine within 4 weeks prior to enrollment;
  • Oversized surgery (not including diagnostic surgery) in the past 8 weeks;
  • Have evidence or history of central nervous system involvement or cranial neuropathy;
  • Treponema pallidum antibody positive, or HIV antibody positive, or HCV antibody positive;
  • HBV examination showed one of the following results: a, HBsAg positive; b, although HBsAg negative, but anti-HBc positive and peripheral blood HBV DNA titer can be measured;
  • Have had herpes zoster and have sequelae or latent infections;
  • Patients with a history of severe heart disease, including but not limited to: New York Heart Association NYHA class II-IV heart failure (see Appendix 3 for NYHA heart failure grading), uncontrolled angina or arrhythmia, heart conduction above II Blocking, myocardial infarction occurred within 6 months
  • Serious illnesses that have been or are currently suffering from any other organ or system (including but not limited to: severely active infections, uncontrolled diabetes, uncontrolled hypertension/hypotension, cerebrovascular disease, gastric ulcers, respiratory diseases, activities) Sexual autoimmune diseases, etc.; and any other medical history that the subject judges to be unsuitable for participating in the trial;
  • Pregnant or lactating female subjects, or those who are unwilling to contraception during the trial
  • Severe allergies, or any component known to be rituximab or other anti-CD20 mAbs or allergic to murine proteins;
  • Subjects had a history of drug abuse or a history of smoking and drinking during the first 6 months of enrollment;
  • The investigator judged that the patient was not suitable for entering any other circumstances of the trial
Contacts and Locations

Contacts
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Contact: Gang Tong +86- 21- 84892211 tonggang@3sbio.com

Locations
Layout table for location information
China, Beijing
The 307 Hospital of People's Liberation Army Recruiting
Beijing, Beijing, China, 100071
Contact: Hang Su    13701396736    suhang307@126.com   
Principal Investigator: hang Su         
Beijing Luhe Hospital Capital Medical University Recruiting
Beijing, Beijing, China, 101100
Contact: dong Yan    13621308215    yd15yt88@163.com   
Principal Investigator: dong Yan         
China, Guangdong
Sun Yat-Sen University Cancer Hospital Recruiting
Guangzhou, Guangdong, China, 510600
Contact: huiqiang huang    020-87343535    huanghq@sysucc.org.cn   
Principal Investigator: huiqiang huang         
China, Hebei
The Fourth Hospital of Hebei Medical University Recruiting
Shijiazhuang, Hebei, China, 050010
Contact: Lihong Liu    13831177920;    13831177920@163.com   
Principal Investigator: Lihong Liu         
China, Heibei
Affiliated Hospital of Hebei University Recruiting
Baoding, Heibei, China, 071000
Contact: aimin Zang    03125983056    hdfygcp@163.com   
Principal Investigator: aimin Zang         
China, Henan
Zhengzhou Central Hospital Recruiting
Zhengzhou, Henan, China, 450007
Contact: shanyong Yi    15516991321    yisy2001@126.com   
Principal Investigator: shanyong Yi         
The First Affiliated Hospita of Zhengzhou University Recruiting
Zhengzhou, Henan, China, 450052
Contact: mingzhi Zhang    13838565629    mingzhi_zhang@126.com   
Principal Investigator: mingzhi Zhang         
China, Shandong
Weihai Municipal Hospital Recruiting
Weihai, Shandong, China, 264200
Contact: xiuzhi Deng    18660377358    18660377358@126.com   
Principal Investigator: xiuzhi Deng         
China, Tianjing
Tianjin Medical University Cancer Institute &Hospital Recruiting
Tianjing, Tianjing, China, 300060
Contact: Lanfang Li    18622221613    Lilanfangmeng@163.com   
Principal Investigator: Lanfang Li         
China, Zhejiang
The Second Affiliated Hospital of Soochow University Recruiting
Suzhou, Zhejiang, China, 215000
Contact: zhixiang Zhuang    13951106391    13951106391@139.com   
Principal Investigator: zhixiang Zhuang         
Sponsors and Collaborators
Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
Tracking Information
First Submitted Date  ICMJE June 6, 2019
First Posted Date  ICMJE June 10, 2019
Last Update Posted Date June 10, 2019
Actual Study Start Date  ICMJE December 18, 2018
Estimated Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
  • AUC [0-t] [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab: Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC [0-t])
  • AUC [0-∞] [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab: Area under the concentration-time curve from time zero extrapolated to infinity (AUC [0-∞])
  • Cmax [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Observed maximum plasma concentration (Cmax)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
  • tmax [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Time to Cmax (tmax)
  • t1/2 [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Elimination half-life (t1/2)
  • MRT [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Mean residence time (MRT)
  • Vz [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:Apparent volume of distribution(Vz)
  • CLz [ Time Frame: For 85 days ]
    To assess PK parameter of plasma 304 or rituximab:apparent clearance (CLz)
  • ADA [ Time Frame: Up to 9 months ]
    To evaluate the incidence of anti-304 and anti-rituximab antibodies
  • Adverse events [ Time Frame: Up to 85 days ]
    To evaluate the adverse events (incidence, severity, outcome, causality with the investigational drug, etc.).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics, Efficacy and Safety of the 304 Injection
Official Title  ICMJE A Study of Pharmacokinetics, Efficacy, and Safety of 304 Injection Compared With Rituximab in B Cell Non-Hodgkin's Lymphoma
Brief Summary The purpose of this study is to evaluate the pharmacokinetic of the experimental drug 304 injection compared with rituximab injection in patients with CD20 positive B-cell non-Hodgkin lymphoma who had previously achieved CR/CRu status but had not deteriorated or relapsed. While to assess the safety and efficacy of the experimental drug 304 injection compared with rituximab injection.
Detailed Description This is a multi-center, randomized, double-blind, parallel controlled, single-dose study to evaluate the pharmacokinetic, safety and efficacy of 304 injection compared with rituximab injection. To avoid the impact of tumor burden on pharmacokinetics, this study will be conducted in CD20 positive B-cell non-Hodgkin lymphoma patients who have achieved CR/CRu status and have not yet deteriorated or relapsed. All patients will be randomly averagely entered into the experimental group and the control group.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE CD20 Positive B Cell NHL
Intervention  ICMJE
  • Drug: 304 injection
    Monoclonal antibodies, 100mg/10ml per injection
  • Drug: rituximab injection
    100mg/10ml per injection ,manufactured by Roche
Study Arms  ICMJE
  • Experimental: experimental group
    304 injection.WILL be administered single dose IV in the patients with CD20 positive B cell NHL
    Intervention: Drug: 304 injection
  • Active Comparator: control group
    Rituximab will be administered single dose IV in the patients with CD20 positive B cell NHL.
    Intervention: Drug: rituximab injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 6, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2019
Estimated Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological examination confirmed CD20-positive B-cell non-Hodgkin's lymphoma patients (according to WHO 2008 lymphoid tissue tumor type, and a corresponding medical history basis);
  • Previous treatments with CR/CRu (see Appendix 1 for lymphoma efficacy criteria) and those with CD20-positive B-cell non-Hodgkin's lymphoma who have not yet worsened and relapsed believe that they can benefit from anti-CD20 monoclonal antibody therapy. The diagnosis of CRu requires complete raw data (using CT findings. The preferred enhanced CT examination)
  • At the time of enrollment, the Eastern Oncology Cooperative Group (ECOG) had a physical status score of ≤1 (see Appendix 2 for the evaluation criteria for the ECOG physical status score) and the expected survival period was more than four months
  • In the screening test, WBC≥3×109/L, HGB≥80g/L, ANC≥1.5×109/L, PLT≥75×109/L, left ventricular ejection fraction (LVEF) ) ≥ 50%
  • Female patients of childbearing age were negative for the blood pregnancy test during the screening period. Patients of childbearing age are willing to contraception after signing the informed consent form until 6 months after the end of the study treatment, including but not limited to: hormonal contraception, or physical contraception, or abstinence
  • Be able to understand and comply with clinical trial protocol requirements and voluntarily sign written informed consent

Exclusion Criteria:

  • In the past 5 years, there have been other medical history of malignant tumors (except for local malignant tumors that have been cured, such as cutaneous basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or breast carcinoma in situ)
  • Those who have used chemotherapy drugs within 4 weeks before enrollment
  • The clinical half-life of more than 5 drugs after taking other clinical trials in three months or other clinical trials (whichever is longer)
  • The last time you used rituximab or other anti-CD20 mAbs for no more than 4 months
  • In the screening test, the liver and kidney function tests have any of the following abnormalities: total bilirubin > 1.5 times the upper limit of normal, ALT > 2.5 times the upper limit of normal, AST > 2.5 times the upper limit of normal, ALP > 2.5 times the upper limit of normal, Blood Cr>1.5 times the upper limit of normal value
  • Hyperthyroidism
  • He was transfused within 2 weeks before enrollment, or hematopoietic cytokine therapy, such as granulocyte colony-stimulating factor (G-CSF), thrombopoietin, erythropoietin, etc.
  • Those who were vaccinated or planned to vaccinate (attenuate) live virus vaccine within 4 weeks prior to enrollment;
  • Oversized surgery (not including diagnostic surgery) in the past 8 weeks;
  • Have evidence or history of central nervous system involvement or cranial neuropathy;
  • Treponema pallidum antibody positive, or HIV antibody positive, or HCV antibody positive;
  • HBV examination showed one of the following results: a, HBsAg positive; b, although HBsAg negative, but anti-HBc positive and peripheral blood HBV DNA titer can be measured;
  • Have had herpes zoster and have sequelae or latent infections;
  • Patients with a history of severe heart disease, including but not limited to: New York Heart Association NYHA class II-IV heart failure (see Appendix 3 for NYHA heart failure grading), uncontrolled angina or arrhythmia, heart conduction above II Blocking, myocardial infarction occurred within 6 months
  • Serious illnesses that have been or are currently suffering from any other organ or system (including but not limited to: severely active infections, uncontrolled diabetes, uncontrolled hypertension/hypotension, cerebrovascular disease, gastric ulcers, respiratory diseases, activities) Sexual autoimmune diseases, etc.; and any other medical history that the subject judges to be unsuitable for participating in the trial;
  • Pregnant or lactating female subjects, or those who are unwilling to contraception during the trial
  • Severe allergies, or any component known to be rituximab or other anti-CD20 mAbs or allergic to murine proteins;
  • Subjects had a history of drug abuse or a history of smoking and drinking during the first 6 months of enrollment;
  • The investigator judged that the patient was not suitable for entering any other circumstances of the trial
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03980379
Other Study ID Numbers  ICMJE SSGJ-304-NHL-I-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
Study Sponsor  ICMJE Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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