Assessing Different FVIII Doses and Frequencies in Immune Tolerance Induction (ITI) with ADVATE Among Hemophilia a Boys with Inhibitor (INITIATE Study)

NCT06864975 | Recruiting Phase 4 DMC

• 1 other identifier: ITI by ADVATE (INITIATE)
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Hemophilia A is a blood coagulation disorder caused by deficient or dysfunctional clotting factor VIII (FVIII) leading to incomplete haemostasis. Patients with severe Hemophilia A are predisposed to recurrent bleeding episodes (BEs) in joints and soft tissues that culminate in debiltating arthropathy and long-term morbidity. Prophylaxis with plasma-derived or recombinant FVIII concentrates effectively restores FVIII levels in patients with Hemophilia A, and significantly reduces the risk of bleeding. A critical concern for patients receiving FVIII replacement therapy is the development of neutralising antibodies (inhibitors) against the treatment. Inhibitors develop in up to 40% of patients with severe Hemophilia A when first exposed to FVIII treatment, typically within the first 20-30 exposure days (EDs) although a residual risk remains until after 75 EDs. Inhibitors preclude the use of FVIII replacement therapy for prevention and treatment of bleeding. Eradication of inhibitors therefore remains an important objective for Hemophilia A patients with inhibitors. Immune tolerance induction (ITI) therapy is the only clinically proven strategy for inhibitor eradication, and at least one attempt should be offered to patients with inhibitors. However, while ITI is well-studied and has a 60- 80% success rate, treatment regimens can be expensive and burdensome to patients. There are limited data on the use of different dose regimen of FVIII ITI in China. The INITIATE Study was designed to observe treatment strategies in patients with hemophilia A with inhibitors, with a focus on evaluating the safety and effectiveness of different dose regimens of ITI. The INITIATE Study includes multiple groups to explore factors that may affect ITI outcomes, and to explore the effects of different treatment methods on patient ITI biomarkers (genomics, transcriptomics, proteins (antibodies).

Conditions

Hemophilia a with Inhibitor

Keywords

immune tolerance induction; ADVATE; FVIII inhibitor; hemophilia A

Outcome Measures

Primary Outcomes (1)

• Success

  1. Criteria I (Negative FVIII inhibitor): At least two inhibitor titers \<0.6 BU/mL; 2. Criteria II (Normal FVIII Recovery): FVIII recovery rate ≥ 66% of expected; 3. Criteria III (Normal FVIII Half-Life): FVIII half-life ≥ 6 hours.

  within 24 months

Study Arms (5)

Low titer inhibitor - Non-daily dose arm

EXPERIMENTAL

Peak inhibitor titer \< 5 BU of historical and during ITI treatment Using FVIII (Advate) 50IU/kg.QoD or 100IU/kg.QoD

Drug: Advate®

Low titer inhibitor - daily dose arm

EXPERIMENTAL

Peak inhibitor titer \< 5 BU of historical and during ITI treatment Using FVIII (Advate) 50IU/kg.QD or 100IU/kg.QD

Drug: Advate®

High titer inhibitor - low dose arm

EXPERIMENTAL

Peak inhibitor titer ≥5BU and \<200BU of historical and during ITI treatment Using FVIII (Advate) 50IU/kg.QD or 100IU/kg.QD

Drug: Advate®

High titer inhibitor - medium or high dose arm

EXPERIMENTAL

Peak inhibitor titer ≥5BU and \<200BU of historical and during ITI treatment Usiing FVIII (Advate) ≥ 100IU/kg.QD

Drug: Advate®

High titer inhibitor with poor prognosis

EXPERIMENTAL

Peak inhibitor ≥200BU of historical and during ITI treatment FVIII (Advate) ≥ 100IU/kg.QD with immunosuppression agent(s)

Drug: Advate®

Interventions

Advate® DRUG

Non-daily dose FVIII 50IU/kg.QoD or 100IU/kg.QoD

High titer inhibitor with poor prognosis

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Severe hemophilia A (FⅧ:C \<2%);
• Positive for FVIII inhibitors;
• No allergic reactions to FVIII concentrates.

You may not qualify if:

• Presence of other coagulation-related diseases,
• Hematological disorders,
• autoimmune diseases
• malignancies

Sponsors & Collaborators

• Runhui WU: lead

Study Sites (1)

Beijing Children's hospitial

Beijing, Beijing Municipality, 100045, China

RECRUITING

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Central Study Contacts

Dr. Wu

CONTACT

+86 010-59616623; runhuiwu@hotmail.com

+86 010-59616623

CONTACT

+86 010-59616623; zekunlee@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician in Charge

Study Record Dates

• First Submitted: March 4, 2025
• First Posted: March 7, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): June 21, 2028
• Last Updated: March 7, 2025

Record last verified: 2025-01

Locations

CN (1)