A Randomized, Double-blind, Placebo-controlled, and Multi-center Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia

NCT06199089 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IIT2023068
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of CM313 in the treatment of immune thrombocytopenia in patients who have failed glucocorticoid therapy.

Conditions

Immune Thrombocytopenia; Treatment

Outcome Measures

Primary Outcomes (1)

• Evaluation of the efficacy after CM313/Placebo treatment at week 8

  Proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count without bleeding at week 8 after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period

  8 weeks

Secondary Outcomes (10)

• Evaluation of the efficacy after CM313/Placebo treatment at each visit period

  24 weeks

• Evaluation of the complete remission rate after CM313/Placebo treatment at each visit period

  24 weeks

• Proportion of subjects with a platelet count ≥ 50 × 10^9/L at each visit period

  24 weeks

• Time to response (TTR)

  24 weeks

• Cumulative weeks of platelet ≥30×10^9/L

  24 weeks

Study Arms (2)

Intervention (CM313)

EXPERIMENTAL

30 from 45 enrolled subjects receive CM313: once a week x 8 doses

Drug: CM313 Injection

Intervention (Placebo)

PLACEBO COMPARATOR

15 from 45 enrolled subjects receive placebo: once a week x 8 doses

Drug: Placebo Injection

Interventions

CM313 Injection DRUG

Intravenous CM313 administration This study adopts a randomized, double-blind, placebo-controlled design method. A total of 45 subjects were randomly assigned to experimental group (CM313, n = 30) and placebo comparator group (Placebo, n = 15) at a ratio of 2:1. Subjects assigned to experimental group were treated with CD38 monoclonal antibody (CM313: 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 efficacy and safety 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 (CM313)

Placebo Injection DRUG

Intravenous Placebo administration This study adopts a randomized, double-blind, placebo-controlled design method. A total of 45 subjects were randomly assigned to experimental group (CM313, n = 30) and placebo comparator group (Placebo, n = 15) at a ratio of 2:1. Subjects assigned to placebo comparator group were treated with placebo of CM313 once a week 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 placebo of CM313 once a week for 8 weeks to observe the efficacy and safety during treatment. The second stage (w9-w24) is the stage of withdrawal from the visit, mainly to observe the safety and continuous efficacy after placebo administration.

Intervention (Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, male or female.
• Before enrollment, the subjects have been clinically diagnosed with primary immune thrombocytopenia for no less than three months according to the American Society of Hematology guidelines 2011 Evidence-Based Practice Guideline (Neunert et al. 2011) or the International Consensus Report for the Investigation and Management of Primary Immune Thrombocytopenia (Provan et al. 2010), as applicable locally.
• Patients have failed glucocorticoid therapy (either due to inefficacy, efficacy could not be maintained, or relapse). Patients were required to have a response history (PLT≥50×10\^9/L) to standard first-line treatment of ITP (glucocorticoid and/or intravenous immunoglobulin).
• Subjects with a platelet count of \<30×10\^9/L within the 24 hours prior to the first dose of the study drug; The mean platelet count of at least two separate assessments (at least 1 week apart) \<30×10\^9/L during the screening visit, and no platelet count \> 35×10\^9/L.
• ECOG performance status score of ≤2.
• Enrollment of subjects receiving maintenance therapy with a stable dosage is permitted, including glucocorticoids (≤0.5 mg/kg of prednisone or equivalent) or TPO receptor agonists. However, at the time of enrollment, subjects are restricted to using only one concomitant medication with a stable dose, and the concomitant medication must have been stable for a minimum of 4 weeks prior to the initial infusion of the study drug.
• For fertile female patients, a negative pregnancy test result is required. Fertile female and male patients must use effective contraception separately during the study and for 4 or 6 months after the cessation of study drug treatment.
• Subjects comprehensively understand and can adhere to the study protocol requirements and willingly signed the informed consent form.

You may not qualify if:

• Subjects with a known allergy to anti-CD38 monoclonal antibodies or excipients, or those who have previously received anti-CD38 monoclonal antibodies with ineffective therapeutic outcomes.
• Subjects who are diagnosed with autoimmune hemolytic anemia or various secondary thrombocytopenic disorders.
• Subjects with history of any thrombotic or embolic events or extensive and severe bleeding, such as hemoptysis, major upper gastrointestinal bleeding, intracranial hemorrhage, or the presence of sepsis or other irregular bleeding within the 12 months preceding the initiation of the first dose of study drug.
• Subjects who have participated in any other investigational drug studies (including vaccine studies) or been exposed to other investigational drugs within the first 4 weeks or 5 half-lives (whichever was longer) prior to the first dose of study drug.
• Subjects who have used anticoagulants or any agents with antiplatelet effects, such as aspirin, within 3 weeks prior to the first dose of study drug.
• Subjects who have received emergency treatment for ITP (e.g., methylprednisolone, platelet transfusion, intravenous immunoglobulin infusion, or thrombopoietin receptor agonist therapy) within 2 weeks prior to the first dose of study drug.
• Subjects who have been treated with medications including azathioprine, danazol, dapsone, cyclosporine A, tacrolimus, and sirolimus within 4 weeks prior to the first dose of study drug. Subjects who have receive anti-CD20 monoclonal antibodies such as rituximab, or medications including cyclophosphamide and vindesine within 6 months prior to the first dose of study drug.
• Subjects who have undergone splenectomy within 6 months prior to the first dose of study drug.
• Subjects who have received live vaccines within 4 weeks prior to the first dose of study drug, or plan to receive any live vaccines during the course of the study.
• Subjects who are diagnosed with Myelodysplastic syndromes (MDS); Subjects with a with a history of malignancy within the 5 years prior to screening (excluding completely cured in situ cervical cancer and non-metastatic skin squamous cell carcinoma or basal cell carcinoma).
• Subjects who have undergone allogeneic stem cell transplantation or organ transplantation.
• Subjects with a clinically significant medical history, as perceived by investigators, that will pose risks to subjects' safety during the study or potentially affect the safety or efficacy analyses, includes major clinical histories such as circulatory system abnormalities, endocrine system abnormalities, nervous system diseases, blood system diseases, immune system diseases, mental diseases and metabolic abnormalities and so on. e.g., subjects with acute myocardial infarction, unstable angina pectoris, or severe arrhythmias (multifocal ventricular premature contractions, ventricular tachycardia, or ventricular fibrillation) within the 6 months before screening ; New York Heart Association (NYHA) class III-IV heart failure; subjects who were known to have had moderate or severe persistent asthma or chronic obstructive pulmonary disease within the 5 years prior to screening, or whose condition was currently poorly controlled;
• Subjects with a history of severe recurrent or chronic infections, or acute infections requiring systemic treatment with antibiotics, antiviral drugs, antiparasitic drugs, anti-amoebic drugs, or antifungal drugs within 4 weeks prior to the first dose and during the screening period, or superficial skin infections requiring systemic treatment within one week prior to the first dose of study drug. Notably, after the resolution of the infection, the subject may be re-screened.
• Subjects with a history of known or suspected immunosuppression, including invasive opportunistic infections such as histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis pneumonia, and aspergillosis, even if the infection has resolved; or unusually frequent, recurrent, or prolonged infections (as judged by the investigator).
• Significant laboratory abnormalities during screening included:

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Tianjin People's Hospital: collaborator
• The Second Affiliated Hospital of Kunming Medical University: collaborator
• Henan Cancer Hospital: collaborator
• Tianjin Medical University Second Hospital: collaborator
• North China University of Science and Technology: collaborator

Study Sites (1)

Chinese Academy of Medical Science and Blood Disease Hospital

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (1)

• Chen Y, Xu Y, Dai J, Sun T, Li H, Hua Z, Zhou Z, Zhou H, Yan Z, Zhao X, Xue F, Liu W, Liu X, Fu R, Wang W, Chi Y, Dong H, Ju M, Dai X, Gu W, Pei X, Yang R, Zhang L. Anti-CD38 monoclonal antibody CM313 for primary immune thrombocytopenia: multicentre, randomised, placebo controlled, phase 2 trial. BMJ. 2025 Oct 21;391:e084314. doi: 10.1136/bmj-2025-084314.

  PMID: 41120215 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Study Officials

• Lei Zhang, MD

  Chinese Academy of Medical Science and Blood Disease Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 25, 2023
• First Posted: January 10, 2024
• Study Start: January 16, 2024
• Primary Completion: November 28, 2024
• Study Completion: December 1, 2024
• Last Updated: December 30, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 12 months to 36 months after study completion
• Access Criteria: Upon request to PI

Locations

CN (1)