A Prospective, One-arm and Open Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia

NCT ID: NCT05694767

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-22
• Study Completion Date: 2023-12-30

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.

Conditions

Immune Thrombocytopenia; Treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention (CM313)

20 enrolled subjects: once a week x 8 doses

Group Type: EXPERIMENTAL

CM313 Injection

Intervention Type: DRUG

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.

Interventions

CM313 Injection

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lei Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Science and Blood Disease Hospital

Locations

Chinese Academy of Medical Science and Blood Disease Hospital

Tianjin, Tianjin Municipality, China

Countries

China

References

Chen Y, Xu Y, Li H, Sun T, Cao X, Wang Y, Xue F, Liu W, Liu X, Dong H, Fu R, Dai X, Wang W, Ma Y, Song Z, Chi Y, Ju M, Gu W, Pei X, Yang R, Zhang L. A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia. N Engl J Med. 2024 Jun 20;390(23):2178-2190. doi: 10.1056/NEJMoa2400409.

Reference Type: DERIVED

PMID: 38899695 (View on PubMed)

Other Identifiers

IIT2022039（2）

Identifier Type: -

Identifier Source: org_study_id