Back to resultsA Prospective, One-arm and Open Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia (2022-CM313-ITP)
Primary Purpose
Immune Thrombocytopenia, Treatment
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
CM313 Injection
Sponsored by
About this trial
This is an interventional treatment trial for Immune Thrombocytopenia
Eligibility Criteria
Inclusion Criteria: Age 18 and above, male or female Conform to the diagnostic criteria of immune Thrombocytopenia (ITP) Diagnosis of ITP ≥3 months, and with a platelet count of <30 X 109/L measured within 2 days prior to inclusion Failure to achieve response or relapse after corticosteroid therapy, and at least one second-line therapy including rituximab or TPORAs. The previous emergency treatment of ITP (e.g. methylprednisolone, platelet transfusion, IVIG transfusion) must be completed at least 2 weeks before the first administration Signed and dated written informed consent With normal hepatic and renal functions ECOG physical state score ≤ 2 points Cardiac function of the New York Society of Cardiac Function ≤ 2 Patients receiving maintenance treatment (including corticosteroids (less than or equal to 0.5mg/kg prednisone), TPO receptor agonists, etc.) must have a stable dose at least 4 weeks before the first administration, and azathioprine, danazol, cyclosporin A, tacrolimus, sirolimus, etc. must be stopped at least 4 weeks before the first administration; The end of rituximab treatment was>3 months；More than 6 months after splenectomy. April 10, 2023 After approval by the Ethics Committee on , subjects no longer require platelet glycoprotein autoantibodies positivity upon enrollment. Exclusion Criteria: Received any treatment of anti-CD38 antibody drug Uncontrollable primary diseases of important organs, such as malignant tumors, liver failure, heart failure, renal failure and other diseases; HIV positive; Accompanied by uncontrollable active infection, including hepatitis B, hepatitis C, cytomegalovirus, EB virus and syphilis positive; Accompanied by extensive and severe bleeding, such as hemoptysis, upper gastrointestinal hemorrhage, intracranial hemorrhage, etc.; At present, there are heart diseases, arrhythmias that need treatment or hypertension that researchers judge is poorly controlled; Patients with thrombotic diseases such as pulmonary embolism, thrombosis and atherosclerosis; Those who have received allogeneic stem cell transplantation or organ transplantation in the past; Patients with mental disorders who cannot normally obtain informed consent and conduct trials and follow-up; Patients whose toxic symptoms caused by pre-trial treatment have not disappeared; Other serious diseases that may limit the subject's participation in this test (such as diabetes; Severe cardiac insufficiency; Myocardial obstruction or unstable arrhythmia or unstable angina pectoris in recent 6 months; Gastric ulcer, etc.); Patients with septicemia or other irregular severe bleeding; Patients taking antiplatelet drugs at the same time; Pregnant women, suspected pregnancies (positive pregnancy test for human chorionic gonadotropin in urine at screening) and lactating patients.
Sites / Locations
- Chinese Academy of Medical Science and Blood Disease HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intervention (CM313)
Arm Description
20 enrolled subjects: once a week x 8 doses
Outcomes
Primary Outcome Measures
To evaluate the efficacy after CM313 treatment within 8 weeks
Proportion of subjects with a platelet count ≥ 50 × 10^9/L within 8 weeks after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period
Safety of CM 313
Incidence, severity, and relationship of treatment emergent adverse events after CM 313 treatment
Secondary Outcome Measures
Other efficacy evaluation
Including: 1. Proportion of subjects with a platelet count ≥ 50 × 10^9/L at week 2, week 4, week 6，week 8，week 10 and week 12 in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period; 2. Proportion of subjects achieving platelet counts ≥ 50×10^9/L at least once in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the first 12 weeks; 3. Proportion of subjects whose platelet counts ≥ 30×10^9/L and at least two times of baseline platelet count in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids within 8 weeks（two consecutive measurements at least 7 days apart）.
Duration from treatment initiation to platelet count ≥30×10^9/L and ≥50×10^9/L
Duration from treatment initiation to platelet count ≥30×10^9/L and ≥50×10^9/L without having received any platelet elevating therapy or having had dose increment of TPO-RA and/or corticosteroids
Cumulative weeks of platelet ≥30×10^9/L and platelet ≥50×10^9/L
Cumulative weeks of platelet ≥30×10^9/L and platelet ≥50×10^9/L without having received any platelet elevating therapy or having had dose increment of TPO-RA and/or corticosteroids
Number of subjects with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale
Changes of the subjects' numbers in WHO bleeding score after CM313 treatment according to the reported World Health Organization's Bleeding Scale. The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss.
Measurements of platelet glycoprotein (GP) autoantibodies
level of anti-GPIIb/IIIa and Ib/IX antibodies before and after CM313 therapy
Measurements of immunoglobulin quantification
The level of IgG, IgA, IgM and IgE quantification before and after CM313 therapy
Measurements of various subsets of immunocompetent cells
To assess the changes of the percentage of B cell subsets，regulatory B cells（Breg），regulatory T cells (Treg)，supressor T cells（Ts），monocyte subcets, helper T cells（Th）subsets and the functionally-polarized CD4+ T cell subsets, etc. in peripheral blood mononuclear cells（PBMCs）before and after CM313 therapy, and to compare with the healthy controls.
Full Information
NCT ID
NCT05694767
First Posted
December 15, 2022
Last Updated
July 29, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
1. Study Identification
Unique Protocol Identification Number
NCT05694767
Brief Title
A Prospective, One-arm and Open Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia
Acronym
2022-CM313-ITP
Official Title
A Prospective, One-arm and Open Clinical Study to Assess Safety and Efficacy of Anti-Human CD38 Monoclonal Antibody CM313 in the Treatment of Primary Immune Thrombocytopenia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 22, 2023 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To evaluate the safety and efficacy of CM313 in the treatment of immune thrombocytopenia in patients who have not responded adequately or relapsed after first-line treatment and at least one second-line therapy including rituximab and/or TPO-RA.
Detailed Description
Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease, which is characterized by decreased platelet count and skin and mucosal bleeding. ITP is a kind of disease with increased platelet destruction and impaired platelet production caused by autoimmunity. Conventional treatment of adult ITP includes first-line glucocorticoid and immunoglobulin therapy, second line TPO and TPO receptor agonist, splenectomy and other immunosuppressive treatments (such as rituximab, vincristine, azathioprine, etc.). ITP is one of the most common hemorrhagic diseases. At present, the treatment response of ITP is not good, and a considerable number of patients need drug maintenance treatment, which seriously affects the quality of life of patients and increases the economic burden of patients. Therefore, there is still a lack of effective treatment for adult ITP, especially for recurrent and refractory ITP patients, which is one of the problems that have attracted more attention and need to be solved urgently.
The main pathogenesis of ITP is the loss of platelet autoantigen immune tolerance, which leads to abnormal activation of humoral and cellular immunity. It is characterized by antibody mediated platelet destruction and insufficient platelet production by megakaryocytes. The residual long-term autoreactive plasma cells may be a source of therapeutic resistance to autoimmune cytopenia. Antiplatelet specific plasma cells have been detected in the spleen of patients with rituximab refractory ITP. Therefore, the strategy of simply eliminating B cells may not work, because LLPC will continue to produce pathogenic antibodies. However, targeting LLPC becomes a new strategy to treat autoimmune diseases.
CM313, a kind of anti-CD38 antibody, is a new type of monoclonal antibody targeting CD38. It targets plasma cells and has carried out some clinical studies in multiple myeloma, with good therapeutic effects. In addition, the clinical trials of similar CD38 monoclonal antibody drugs, such as daratumumab, in the treatment of autoimmune diseases, including membranous nephropathy, systemic lupus erythematosus (SLE) and ITP, are also being carried out simultaneously. We assume that autologous reaction LLPC may be the cause of treatment failure in some ITP patients. Therefore, the use of CD38 monoclonal antibody to clear long-term surviving plasma cells in ITP patients may be a new strategy for treating ITP patients.
Therefore, the investigators designed this clinical trial to evaluate the safety and efficacy of CM313 in the treatment of immune thrombocytopenia in patients who are steroid-refractory or steroid-dependent, and fail to respond to at least one previous second-line therapy, including rituximab and/ or TPO agonist.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune Thrombocytopenia, Treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention (CM313)
Arm Type
Experimental
Arm Description
20 enrolled subjects: once a week x 8 doses
Intervention Type
Drug
Intervention Name(s)
CM313 Injection
Intervention Description
intravenous CM313 administration
This study adopts a prospective, single arm, open design method. Twenty subjects were enrolled in the study and were treated with CD38 monoclonal antibody (CM 313: 16mg/kg/w) for 8 weeks.
The first stage is the main research stage (d1-w8), which is the core treatment period. The subjects will receive intravenous infusion of 16mg/kg CM313 once a week for 8 weeks to observe the safety and efficacy during treatment.
The second stage (w9-w24) is the stage of withdrawal from the visit, mainly to observe the safety and continuous efficacy of CM313 after treatment.
Primary Outcome Measure Information:
Title
To evaluate the efficacy after CM313 treatment within 8 weeks
Description
Proportion of subjects with a platelet count ≥ 50 × 10^9/L within 8 weeks after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period
Time Frame
8 weeks
Title
Safety of CM 313
Description
Incidence, severity, and relationship of treatment emergent adverse events after CM 313 treatment
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Other efficacy evaluation
Description
Including: 1. Proportion of subjects with a platelet count ≥ 50 × 10^9/L at week 2, week 4, week 6，week 8，week 10 and week 12 in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period; 2. Proportion of subjects achieving platelet counts ≥ 50×10^9/L at least once in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the first 12 weeks; 3. Proportion of subjects whose platelet counts ≥ 30×10^9/L and at least two times of baseline platelet count in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids within 8 weeks（two consecutive measurements at least 7 days apart）.
Time Frame
12 weeks
Title
Duration from treatment initiation to platelet count ≥30×10^9/L and ≥50×10^9/L
Description
Duration from treatment initiation to platelet count ≥30×10^9/L and ≥50×10^9/L without having received any platelet elevating therapy or having had dose increment of TPO-RA and/or corticosteroids
Time Frame
12 weeks
Title
Cumulative weeks of platelet ≥30×10^9/L and platelet ≥50×10^9/L
Description
Cumulative weeks of platelet ≥30×10^9/L and platelet ≥50×10^9/L without having received any platelet elevating therapy or having had dose increment of TPO-RA and/or corticosteroids
Time Frame
24 weeks
Title
Number of subjects with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale
Description
Changes of the subjects' numbers in WHO bleeding score after CM313 treatment according to the reported World Health Organization's Bleeding Scale. The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss.
Time Frame
24 weeks
Title
Measurements of platelet glycoprotein (GP) autoantibodies
Description
level of anti-GPIIb/IIIa and Ib/IX antibodies before and after CM313 therapy
Time Frame
24 weeks
Title
Measurements of immunoglobulin quantification
Description
The level of IgG, IgA, IgM and IgE quantification before and after CM313 therapy
Time Frame
24 weeks
Title
Measurements of various subsets of immunocompetent cells
Description
To assess the changes of the percentage of B cell subsets，regulatory B cells（Breg），regulatory T cells (Treg)，supressor T cells（Ts），monocyte subcets, helper T cells（Th）subsets and the functionally-polarized CD4+ T cell subsets, etc. in peripheral blood mononuclear cells（PBMCs）before and after CM313 therapy, and to compare with the healthy controls.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 and above, male or female
Conform to the diagnostic criteria of immune Thrombocytopenia (ITP)
Diagnosis of ITP ≥3 months, and with a platelet count of <30 X 109/L measured within 2 days prior to inclusion
Failure to achieve response or relapse after corticosteroid therapy, and at least one second-line therapy including rituximab or TPORAs.
The previous emergency treatment of ITP (e.g. methylprednisolone, platelet transfusion, IVIG transfusion) must be completed at least 2 weeks before the first administration
Signed and dated written informed consent
With normal hepatic and renal functions
ECOG physical state score ≤ 2 points
Cardiac function of the New York Society of Cardiac Function ≤ 2
Patients receiving maintenance treatment (including corticosteroids (less than or equal to 0.5mg/kg prednisone), TPO receptor agonists, etc.) must have a stable dose at least 4 weeks before the first administration, and azathioprine, danazol, cyclosporin A, tacrolimus, sirolimus, etc. must be stopped at least 4 weeks before the first administration; The end of rituximab treatment was>3 months；More than 6 months after splenectomy.
April 10, 2023 After approval by the Ethics Committee on , subjects no longer require platelet glycoprotein autoantibodies positivity upon enrollment.
Exclusion Criteria:
Received any treatment of anti-CD38 antibody drug
Uncontrollable primary diseases of important organs, such as malignant tumors, liver failure, heart failure, renal failure and other diseases;
HIV positive;
Accompanied by uncontrollable active infection, including hepatitis B, hepatitis C, cytomegalovirus, EB virus and syphilis positive;
Accompanied by extensive and severe bleeding, such as hemoptysis, upper gastrointestinal hemorrhage, intracranial hemorrhage, etc.;
At present, there are heart diseases, arrhythmias that need treatment or hypertension that researchers judge is poorly controlled;
Patients with thrombotic diseases such as pulmonary embolism, thrombosis and atherosclerosis;
Those who have received allogeneic stem cell transplantation or organ transplantation in the past;
Patients with mental disorders who cannot normally obtain informed consent and conduct trials and follow-up;
Patients whose toxic symptoms caused by pre-trial treatment have not disappeared;
Other serious diseases that may limit the subject's participation in this test (such as diabetes; Severe cardiac insufficiency; Myocardial obstruction or unstable arrhythmia or unstable angina pectoris in recent 6 months; Gastric ulcer, etc.);
Patients with septicemia or other irregular severe bleeding;
Patients taking antiplatelet drugs at the same time;
Pregnant women, suspected pregnancies (positive pregnancy test for human chorionic gonadotropin in urine at screening) and lactating patients.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yunfei Chen, MD
Phone
+8618502220788
Email
chenyunfei@ihcams.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lei Zhang, MD
Organizational Affiliation
Chinese Academy of Medical Science and Blood Disease Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chinese Academy of Medical Science and Blood Disease Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunfei Chen, MD
Phone
+86-22-23909009
Email
chenyunfei@ihcams.ac.cn
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Researchers qualified can request the dataset, including de-identified individual subject data. Data may be requested from PI from 12 months 36 months after study completion.
IPD Sharing Time Frame
12 months to 36 months after study completion
IPD Sharing Access Criteria
Upon request to PI
Learn more about this trial
A Prospective, One-arm and Open Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia
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