Recruiting

FVIII Inhibitors

Sponsor:

Emory University

Code:

NCT04023019

Conditions

Hemophilia A

Eligibility Criteria

Sex: Male

Age: 0+

Healthy Volunteers: Not accepted

Interventions

Nuwiq

Octanate

Wilate

Emicizumab

Recombinant factor VIIa (rFVIIa)

Study Details

Brief summary:

This is a non-interventional, multicenter, observational, international study in male persons with haemophilia A who have developed inhibitors to any replacement coagulation factor VIII (FVIII) product. The purpose of the study is to capture different approaches in the management of persons with haemophilia A and FVIII inhibitors, document current immune tolerance induction approaches, and evaluate the efficacy and safety of immune tolerance induction, including the combination of FVIII and emicizumab. Patients will be assigned to 1 of 3 groups based on the treatments they receive, and may switch to another group if their treatment is changed. Participants will be followed after a maximum observational period of 5 years.

Conditions

Hemophilia A

Study ID

NCT04023019

Start date

Mar 17, 2020

Status verified date

Aug, 2025

Completion date

Jun, 2029

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 0+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Male persons with haemophilia A, of any severity, who have a historical inhibitor titer ≥ 0.6 BU/mL, including those who have failed previous immune tolerance induction (ITI) attempt(s)
  • Persons undergoing ITI with Nuwiq, octanate, or wilateor undergoing ITI with Nuwiq®, octanate® or wilate® and receiving prophylactic therapy with emicizumab, activated prothrombin complex concentrate (aPCC), or activated recombinant factor VII (rFVIIa)
  • Participants or participants' parent(s)/legal guardian(s) must be capable of giving signed informed consent and be able to understand the trial documents

Exclusion Criteria:

  • Participants are excluded from the trial if any coagulation disorder other than haemophilia A is diagnosed
  • Partly retrospective patients will be excluded if detailed documentation on treatment, all bleeding episodes, inhibitor titers, and FVIII levels is not available for the retrospective period

Study Design

Enrollment

120 participants

Anticipated

Interventions and Outcome Measures

Arms

Group 1: ITI with Nuwiq, octanate, or wilate

Participants receiving immune tolerance induction with either Nuwiq, octanate, or wilate. As needed, aPCC/rFVIIa will be administered to treat bleeding episodes or during surgery and for prophylaxis.

Group 2: ITI with Nuwiq, octanate, or wilate with emicizumab

Participants receiving immune tolerance induction with either Nuwiq, octanate, or wilate, in combination with emicizumab prophylaxis. As needed, aPCC/rFVIIa will be administered to treat bleeding episodes or during surgery.

Group 3: Prophylaxis with emicizumab, aPCC, or rFVIIa

Participants receiving routine prophylaxis with emicizumab, aPCC, or rFVIIa without immune tolerance induction. On-demand aPCC/rFVIIa can be used as needed to treat bleeding episodes or during surgery.

Interventions

Nuwiq

Nuwiq is a recombinant FVIII concentrate from a human cell line. It is administered via intravenous injection at a dosage determined by the investigator's discretion, in consideration of the participants' clinical condition and prescribing information.

Octanate

Octanate is a high-purity human Factor VIII / von Willebrand Factor (VWF) concentrate. It is administered via intravenous injection at a dosage determined by the investigator's discretion, in consideration of the participants' clinical condition and prescribing information.

Wilate

Wilate is a high-purity human von Willebrand Factor (VWF)/Factor VIII concentrate. It is administered via intravenous injection at a dosage determined by the investigator's discretion, in consideration of the participants' clinical condition and prescribing information.

Emicizumab

Emicizumab is a therapeutic antibody which brings activated factor IX and factor X together It is administered via subcutaneous injection at a dosage determined by the investigator's discretion, in consideration of the participants' clinical condition and prescribing information.

Recombinant factor VIIa (rFVIIa)

Recombinant factor VIIa (rFVIIa) is a blood factor VII manufactured using recombinant technology. It is administered via intravenous injection at a dosage determined by the investigator's discretion, in consideration of the participants' clinical condition and prescribing information.

Activated prothrombin complex concentrate (aPCC)

Activated prothrombin complex concentrate (aPCC) is an anti-inhibitor coagulant complex acting on multiple pathways to facilitate coagulation. It is administered via intravenous injection at a dosage determined by the investigator's discretion, in consideration of the participants' clinical condition and prescribing information.

Primary outcome measure

  • Proportion of participants achieving inhibitor titer < 0.6 Bethesda units (BU)/mL L for at least 2 consecutive measurements [ Time Frame: Up to 5 years ]
  • Proportion of participants achieving FVIII recovery ≥ 66% of the predefined reference value of 1.5% IU/kg body weight (Groups 1 and 2) [ Time Frame: Up to 5 years ]
  • Proportion of participants achieving FVIII half-life ≥ 6 h (Groups 1 and 2) [ Time Frame: Up to 5 years ]
  • Annualized bleeding rate [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Central contacts

Robert Sidonio, MD, MSc

404-785-1637robert.sidonio.jr@emory.edu

Carmen Escuriola-Ettingshausen, MD

+4961059638909carmen.escuriola@hzrm.de

Locations

Arthur M. Blank Hospital

Recruiting

Atlanta, Georgia, United States, 30329

Contacts

Robert Sidonio, MD, MSc

404-785-1637robert.sidonio.jr@emory.edu

Principal Investigator:

Robert Sidonio, MD, MSc

More Information

Sponsor

Emory University

Last update posted

Sep 5, 2025

Last verified

Aug, 2025

Keywords

  • Blood disorders

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Emory University on 2025-09-05.