Phase I/II Study of Anti-CD38 Monoclonal Antibody in Refractory Severe Aplastic Anemia

A Phase I/II Study on the Safety and Efficacy of CD38 Monoclonal Antibody in the Treatment of Refractory Severe Aplastic Anemia

This is a phase I/II clinical study in adult patients with refractory severe aplastic anemia (SAA). Eligible patients must meet the criteria for refractory SAA and have a platelet count (PLT) <30 × 10^9/L and/or hemoglobin (HGB) <90 g/L at enrollment. If the phase I results demonstrate an acceptable safety profile and allow determination of the maximum tolerated dose (MTD), the phase II part will be initiated directly to evaluate the efficacy of isatuximab.

Study Overview

• Status: Recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: Isatuximab

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lele Zhang, PhD; Phone Number: 15811139278; Email: zhanglele@ihcams.ac.cn

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 301617
      • Recruiting
      • Red Blood Cell Diseases Center and Regenerative Medicine Center
      • Contact: Lele Zhang, PhD; Phone Number: 15811139278; Email: zhanglele@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with primary acquired aplastic anemia according to the 2024 British Society for Haematology guideline, Guidelines for the Diagnosis and Management of Adult Aplastic Anaemia, and the Chinese Guideline for the Diagnosis and Treatment of Aplastic Anemia (2022 edition) issued by the Hematology Branch of the Chinese Medical Association.
• Previously diagnosed with severe aplastic anemia (SAA) or very severe aplastic anemia (VSAA), with no response or relapse after receiving anti-thymocyte/anti-lymphocyte globulin (ATG/ALG) in combination with standard-dose cyclosporine for at least 6 months, and standard-dose thrombopoietin receptor agonist (TPO-RA) therapy for at least 4 months.
• Hemoglobin <90 g/L or platelet count <30×10^9/L
• Unsuitable for or unwilling to undergo hematopoietic stem cell transplantation, with no better available treatment options.
• Age ≥18 years, regardless of gender.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
• Willing and able to comply with the requirements for this study and written informed consent.

Exclusion Criteria:

• Diagnosed with congenital bone marrow failure syndromes
• Bone marrow reticulin fibrosis grade ≥2
• Subjects with a paroxysmal nocturnal hemoglobinuria (PNH) clone ≥50% or active hemolysis
• Subjects with clonal cytogenetic abnormalities characteristic of myelodysplastic syndromes, except +8, del(20q), and -Y
• Active bacterial, viral, or fungal infection within 2 weeks before the first dose of the investigational drug, excluding common cold and onychomycosis, or any other serious infection. Any anti-infective treatment course for infection must have been completed at least 2 weeks before the first dose. Subjects with a history of HIV infection or positive HIV antibody during screening; positive Treponema pallidum antibody during screening; active tuberculosis, defined as chest imaging or other relevant examinations within 3 months before the first dose of the investigational drug or during screening suggesting active tuberculosis infection; or active hepatitis during screening, defined as hepatitis B surface antigen (HBsAg) positivity, or hepatitis B core antibody (HBcAb) positivity with hepatitis B virus (HBV) DNA ≥30 IU/mL, or hepatitis C virus (HCV) antibody positivity with HCV RNA positivity
• Active bleeding in the gastrointestinal tract, respiratory tract, central nervous system, or other sites
• A history of any clinically significant disease that, in the investigator's opinion, would pose a safety risk to the subject if participating in the study, or would affect the evaluation of efficacy or safety if the disease/condition worsens during the study, including but not limited to: a. cardiovascular diseases, such as a history of acute myocardial infarction or unstable angina within the past year, severe arrhythmia such as frequent multifocal premature ventricular contractions, ventricular tachycardia, or ventricular fibrillation, congestive heart failure, arterial or venous thrombosis, or New York Heart Association (NYHA) class III-IV cardiac function; b. a history of psychiatric disorders, severe cerebrovascular disease, or cognitive sequelae
• Use of agents targeting B cells or plasma cells within 3 months before the first dose of the investigational drug or anticipated use during the clinical trial
• Treatment with anti-lymphocyte globulin or anti-thymocyte globulin within 6 months before the first dose of the investigational drug
• Treatment with tacrolimus, sirolimus, cyclophosphamide, anti-CD52 monoclonal antibody, or similar therapies within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of the investigational drug
• Planned participation in another clinical trial, or prior exposure to another investigational product before the first dose, with an interval of less than 4 weeks or 5 half-lives of the drug, whichever is shorter
• Receipt of a live attenuated vaccine within 4 weeks before the first dose of the investigational drug or planned receipt during the study, or receipt of a COVID-19 vaccine within 7 days before dosing
• Prior treatment targeting CD38
• Women who are pregnant or breastfeeding, or who plan to become pregnant or breastfeed during the study
• Patients considered to be ineligible for the study by the investigator for reasons other than the above

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Isatuximab; The phase I part is the dose-escalation stage dose escalation will follow a standard 3+3 design. The phase II part is a single-arm study using Simon's two-stage design.

Drug: Isatuximab; Phase I: Eligible subjects will receive isatuximab at 5 mg/kg per dose or 10 mg/kg per dose. The treatment period will last 6 weeks. Isatuximab will be administered by intravenous infusion once weekly (QW) for six consecutive doses. Phase II: Eligible subjects will receive isatuximab by intravenous infusion once weekly for six consecutive doses. The specific dose will be the recommended phase II dose from the phase I part.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 6 to assess the adverse event	Within 12 weeks post treatment
Overall response rate	Percentage of patients with hematological response, including complete response (CR) or partial response (PR). Hematological response is evaluated by hemoglobin (Hb), platelet count (PLT) and absolute neutrophil count (ANC).	Within 12 weeks post treatment

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: Sanofi
• Investigators: Principal Investigator: Jun Shi, PhD, Institute of Hematology & Blood Diseases Hosptial, Chinese Academy of Medical Science and Peking Union Medical School

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 15, 2026
• First Submitted That Met QC Criteria: July 15, 2026
• First Posted (Actual): July 20, 2026

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: July 15, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Isatuximab; Severe aplastic anemia
• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Hemic and Lymphatic Diseases; Anemia, Aplastic; isatuximab
• Other Study ID Numbers: ISAA-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No