Treatment of Hemophilia A Patients With FVIII Inhibitors
MOTIVATE
MOdern Treatment of Inhibitor-PositiVe PATiEnts With Haemophilia A - An International Observational Study
1 other identifier
observational
120
2 countries
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Mar 2020
Longer than P75 for all trials
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 12, 2019
CompletedFirst Posted
Study publicly available on registry
July 17, 2019
CompletedStudy Start
First participant enrolled
March 17, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2029
September 5, 2025
August 1, 2025
8.7 years
July 12, 2019
August 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Proportion of participants achieving inhibitor titer < 0.6 Bethesda units (BU)/mL L for at least 2 consecutive measurements
The proportion of participants in Groups 1 and 2 achieving inhibitor titer \< 0.6 Bethesda units (BU)/mL L for at least 2 consecutive measurements will be determined. FVIII inhibitor titer is measured at baseline and throughout the study, according to standard of care.
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)
The proportion of participants in Groups 1 and 2 achieving FVIII recovery ≥ 66% of the predefined reference value of 1.5% IU/kg body weight will be determined. Once inhibitor has become negative (\< 0.6 BU/mL), FVIII plasma levels are measured prior to and approximately 15 to 30 minutes after FVIII to evaluate FVIII recovery.
Up to 5 years
Proportion of participants achieving FVIII half-life ≥ 6 h (Groups 1 and 2)
The proportion of participants in Groups 1 and 2 achieving FVIII half-life ≥ 6 h will be determined. Once inhibitor has become negative (\< 0.6 BU/mL), FVIII plasma levels are measured prior to and at 15-30 minutes and 2, 4, 8-12, and 24 hours after administration of the immune tolerance induction (or prophylactic FVIII) to evaluate half-life; when FVIII trough levels are \> 1% during regular prophylaxis, half-life can be evaluated from fewer samples or using a population pharmacokinetic model.
Up to 5 years
Annualized bleeding rate
Annualized rate of all bleeding episodes will be reported and compared between all 3 study groups.
Up to 5 years
Secondary Outcomes (11)
Time to achieve immune tolerance induction outcome
Up to 5 years
Frequency of emicizumab, aPCC, and rFVIIa use during immune tolerance induction
Up to 5 years
Rate of FVIII inhibitor relapse
Up to 5 years
Frequency of bleeding episodes
Up to 5 years
Severity of bleeding episodes
Up to 5 years
- +6 more secondary outcomes
Study Arms (3)
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 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 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 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 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) 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) 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.
Eligibility Criteria
The study population includes males with haemophilia A who have delveloped inhibitors to any FVIII product. Participants starting treatment after study inclusion will have all data recorded prospectively while those who have already started treatment can enter if detailed retrospective documentation is available. Participants will be observed for a maximum of 5 years.
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Emory Universitylead
- Octapharmacollaborator
Study Sites (2)
Arthur M. Blank Hospital
Atlanta, Georgia, 30329, United States
HZRM Hämophilie-Zentrum Rhein Main
Mörfelden-Walldorf, 64546, Germany
Related Publications (1)
Escuriola Ettingshausen C, Sidonio RF Jr. Design of an international investigator-initiated study on MOdern Treatment of Inhibitor-positiVe pATiEnts with haemophilia A (MOTIVATE). Ther Adv Hematol. 2021 Sep 23;12:20406207211032452. doi: 10.1177/20406207211032452. eCollection 2021.
PMID: 34589194DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert Sidonio, MD, MSc
Emory University
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
July 12, 2019
First Posted
July 17, 2019
Study Start
March 17, 2020
Primary Completion (Estimated)
December 1, 2028
Study Completion (Estimated)
June 1, 2029
Last Updated
September 5, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share