Hemophilia A With Inhibitors
Conditions
Keywords
Hemophilia A, Inhibitors, Elranatamab
Brief summary
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.
Interventions
DRUGElranatamab
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.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (AES) | 1 year | AES was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients who achieve successful inhibitor eradication | 1 year | the number of patients with successful inhibitor eradication divided by the total number of patients in the study, expressed as a percentage. |
Countries
China
Contacts
CONTACTWei Liu
CONTACTLei Zhang
PRINCIPAL_INVESTIGATORLei Zhang
Chinese Academy of Medical Science and Blood Disease Hospital
Outcome results
None listed