A Study of Elranatamab for Inhibitor Eradication in Patients With Hemophilia A

N/ANot Yet RecruitingNCT07788469

Institute of Hematology & Blood Diseases Hospital, China20 enrolled

Overview

This is a prospective, single-arm, open-label, exploratory clinical study designed to evaluate the safety and efficacy of Elranatamab for inhibitor eradication in adults with moderate-to-severe hemophilia A with inhibitors. A total of 15-20 patients aged ≥18 years will be enrolled. Elranatamab will be administered with a stepwise dose-escalation regimen of 12 mg on Day 1 and 32 mg on Day 4 during Week 1, followed by the target dose of 38 mg once weekly during Weeks 2-3. Patients will then enter a 4-week follow-up period. If the inhibitor titer decreases by \<20% from baseline at Week 3, two additional weekly doses of 38 mg may be administered before follow-up. Treatment response will be assessed according to changes in inhibitor titers following treatment.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemophilia A With Inhibitors

Interventions

Patients receive Elranatamab at 12 mg on Day 1 and 32 mg on Day 4 during Week 1, followed by the target dose of 38 mg once weekly during Weeks 2-3. Patients will then enter a 4-week follow-up period. If the inhibitor titer decreases by \<20% from baseline at Week 3, two additional weekly doses of 38 mg may be administered before follow-up. If the inhibitor titer decreases by \>20% from baseline at Week 3, no further treatment will be given, and patients will proceed directly to follow-up.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female patients with moderate-to-severe hemophilia A (factor VIII activity \<2%). * Aged 18 to 65 years, inclusive. * Positive factor VIII inhibitor detected on at least two consecutive occasions (inhibitor titer \>0.6 BU/mL). * Baseline factor VIII inhibitor titer \>10 BU/mL at the time of enrollment. Exclusion Criteria: * Known hypersensitivity to Elranatamab or any of its excipients. * Presence of other autoimmune diseases or a need for immunosuppressive therapy for reasons unrelated to this study. * History of malignancy within 5 years prior to screening, with the exception of adequately treated carcinoma in situ of the cervix or non-metastatic cutaneous squamous cell carcinoma or basal cell carcinoma. * History of severe recurrent or chronic infections, or acute infection requiring systemic treatment with antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungal agents within 4 weeks before the first dose or during the screening period, or superficial skin infection requiring systemic therapy within 1 week before the first dose. * Clinically significant laboratory abnormalities at screening, including: 1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 × the upper limit of normal (ULN). 2. Total bilirubin \>1.5 × ULN (subjects with documented Gilbert syndrome are not excluded based on this criterion); 3. Absolute neutrophil count \<1,500/mm³; 4. Hemoglobin \<9 g/dL or immunoglobulin G (IgG) \<500 mg/dL; 5. Absolute lymphocyte count \<500/mm³; 6. Creatinine clearance (CrCl) \<30 mL/min. * Positive test for HIV antibody or syphilis antibody. * Positive hepatitis B surface antigen (HBsAg); or positive hepatitis B core antibody (anti-HBc) with detectable HBV DNA by polymerase chain reaction (PCR). Subjects positive for hepatitis C virus (HCV) antibody are excluded. * Women who are pregnant or breastfeeding, or who plan to become pregnant or breastfeed during the study; men whose partners plan to become pregnant during the study. * Subjects with psychiatric disorders that impair their ability to provide informed consent or comply with study procedures and follow-up. * Subjects with unresolved toxicities from prior therapies before study participation. * Any other condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events (AES)

AES was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.

Time frame: 1 year

Secondary Outcomes

The proportion of patients who achieve successful inhibitor eradication

the number of patients with successful inhibitor eradication divided by the total number of patients in the study, expressed as a percentage.