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

A Single-Arm, Open-Label, Exploratory Clinical Study to Evaluate the Safety and Efficacy of Elranatamab for Inhibitor Eradication in Patients With Moderate-to-Severe Hemophilia A With Inhibitors and Poor Prognosis for Inhibitor Eradication

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.

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.