Hemophilia AMOTIVATENCT04023019
Treatment of Hemophilia A Patients With FVIII Inhibitors
An observational study of Hemophilia A, run by Emory University at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Nuwiq, Octanate and Wilate
- Type of treatment
- Injection or infusion
- How many people
- 120 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 17 Mar 2020to Jun 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Study population: 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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
Arthur M. Blank Hospital
Atlanta, Georgia, 30329
Robert Sidonio, MD, MSc, 404-785-1637, robert.sidonio.jr@emory.edu
Robert Sidonio, MD, MSc
Germany1 site, 1 recruiting
- Recruiting
HZRM Hämophilie-Zentrum Rhein Main
Mörfelden-Walldorf, 64546
Carmen Escuriola-Ettingshausen, MD, +4961059638909, carmen.escuriola@hzrm.de
Carmen Escuriola-Ettingshausen, MD
About this study
Official title: MOdern Treatment of Inhibitor-PositiVe PATiEnts With Haemophilia A - An International Observational Study
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.
Read the detailed description
This study will capture different approaches in the management of persons with haemophilia A (HA) and inhibitors. HA is a serious blood coagulation disorder caused by a deficiency in FVIII that results in a failure to produce FVIII in sufficient quantities to achieve satisfactory haemostasis. Patients with HA are predisposed to recurrent bleeds into joints and soft tissues that culminate in debilitating arthropathy and long-term morbidity. HA can be effectively treated with replacement FVIII concentrates, obtained by fractionation of human plasma (pdFVIII) or using recombinant technology (rFVIII). In patients receiving FVIII replacement therapy, inhibitors can develop that neutralise the effect of treatment. Inhibitors develop in ~35% of patients who have not been previously exposed to FVIII treatment and ~1% of patients who have undergone previous FVIII treatment. Inhibitor development has major adverse implications on bleeding rates, morbidity, mortality and quality of life.
Immune tolerance induction (ITI), which involves prolonged treatment with plasma-derived (pdFVIII) or recombinant FVIII (rFVIII), is the only clinically proven strategy for eradication of inhibitors and is recommended as the primary treatment option in European and US guidelines. Bypassing agents (activated recombinant factor VII [rFVIIa] and activated prothrombin complex concentrate [aPCC]) are used to manage bleeding episodes (BEs) and for prophylaxis or in surgical settings in patients with FVIII inhibitors. The bispecific factor IX (FIX) and factor X (FX) monoclonal antibody emicizumab was approved in the US in November 2017, and in Europe in February 2018.
The overall objective of this study is to capture different approaches in the management of participants with HA and inhibitors, document current ITI approaches, and evaluate efficacy and safety of ITI, including the combination of FVIII and emicizumab. Patients will be assigned to 1 of 3 groups based on the treatments they receive:
- Group 1 receives ITI with Nuwiq, octanate, or wilate, with aPCC or rFVIIa administered as needed
- Group 2 receives ITI with Nuwiq, octanate, or wilate, in combination with emicizumab, with aPCC or rFVIIa administered as needed
- Group 3 receives routine prophylaxis with emicizumab, aPCC or rFVIIa without ITI
- Conditions
- Hemophilia A
- Being tested
- Nuwiq, Octanate, Wilate, Emicizumab, Recombinant factor VIIa (rFVIIa)
- Keywords
- Blood disorders
- Medical subject headings
- Hemophilia A, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NuwiqBiological
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.
OctanateBiological
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.
WilateBiological
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.
EmicizumabBiological
Also called Hemlibra
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)Biological
Also called NovoSeven
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)Biological
Also called FEIBA
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Nuwiq; Biological: Octanate; Biological: Wilate; Biological: Recombinant factor VIIa (rFVIIa); Biological: Activated prothrombin complex concentrate (aPCC) | |
| 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. Receives: Biological: Nuwiq; Biological: Octanate; Biological: Wilate; Biological: Emicizumab; Biological: Recombinant factor VIIa (rFVIIa); Biological: Activated prothrombin complex concentrate (aPCC) | |
| 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. Receives: Biological: Emicizumab; Biological: Recombinant factor VIIa (rFVIIa); Biological: Activated prothrombin complex concentrate (aPCC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to 5 years
Annualized bleeding rate
Annualized rate of all bleeding episodes will be reported and compared between all 3 study groups.
Measured: Up to 5 years
Secondary outcomes (11)
Time to achieve immune tolerance induction outcome
The time it takes to achieve immune tolerance induction will be assessed in Groups 1 and 2. Immune tolerance induction success is defined as inhibitor titer < 0.6 BU/mL for at least 2 consecutive measurements, FVIII recovery ≥ 66% of the predefined reference value of 1.5% IU/kg body weight, and half-life of FVIII ≥ 6 h.
Measured: Up to 5 years
Frequency of emicizumab, aPCC, and rFVIIa use during immune tolerance induction
The number of times that participants in Groups 1 and 2 used emicizumab, aPCC, and rFVIIa during immune tolerance induction will be reported.
Measured: Up to 5 years
Rate of FVIII inhibitor relapse
Rate of FVIII inhibitor relapses for participants in Groups 1 and 2 during an observational follow-up period in participants who have achieved complete immune tolerance induction success. Relapse is defined as inhibitor titer ≥ 0.6 BU/mL on ≥ 2 consecutive occurrences during the observational follow-up period after having achieved complete success and a prophylactic dose of ≤ 50 IU FVIII/kg every other day.
Measured: Up to 5 years
Frequency of bleeding episodes
Frequency of all bleeding episodes (BEs), including all treated BEs, all spontaneous BEs, all joint BEs, and target joint BEs over time (≥ 3 bleeds in the same joint within 24 weeks) will be compared between study groups.
Measured: Up to 5 years
Severity of bleeding episodes
Severity of all bleeding episodes (BEs), including all treated BEs, all spontaneous BEs, all joint BEs, and target joint BEs over time (≥ 3 bleeds in the same joint within 24 weeks) will be compared between study groups. Assessment of BE severity will be defined as:
- Minor BEs are superficial muscle or soft tissue and oral bleeds
- Moderate to major BEs are joint bleeds, bleeding into muscles, into oral cavity, known trauma
- Major to life threatening BEs are bleedings in the cranium, abdomen, digestive system or chest, central nervous system bleeds, bleeding in the area of the pharynx or bleeds of the pelvic muscles, eyes/retina, fractures or head trauma
Measured: Up to 5 years
Number of infusions required to control bleeding episodes
The number of infusions required to control bleeding episodes will be compared between study groups.
Measured: Up to 5 years
Frequency of bleeding with surgical procedures
The frequency of bleeding during and after surgical procedures will be compared between study groups.
Measured: Up to 5 years
Severity of bleeding with surgical procedures
The severity of bleeding during and after surgical procedures will be compared between study groups. The severity of bleeding during surgery will be defined as:
- Excellent - Intraoperative blood loss was lower than or equal to the average expected blood loss for the type of procedure performed in a patient with normal haemostasis and of the same sex, age, and stature
- Good - Intraoperative blood loss was higher than the average expected blood loss but lower or equal to the maximal expected blood loss for the type of procedure in a patient with normal haemostasis
- Moderate - Intraoperative blood loss was higher than the maximum expected blood loss for the type of procedure performed in a patient with normal haemostasis, but haemostasis was controlled
- None - Haemostasis was uncontrolled, necessitating a change in the treatment regimen
Measured: Up to 5 years
Proportion of participants experiencing adverse drug reactions
The proportion of participants experiencing adverse drug reactions will be compared between study groups.
Measured: Up to 5 years
Number of thrombotic events
The number of thrombotic events will be compared between study groups.
Measured: Up to 5 years
Treatment costs
The cost (in dollars) of treatment will be compared between study groups.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2019
- Study start17 Mar 2020
- Primary completionDec 2028 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Octapharma
- Responsible party
- Principal investigator, Robert Sidonio, Emory University
- Investigators
- Robert Sidonio, MD, MSc, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04023019
- Sponsor's protocol ID
- IRB00113316
- Other IDs
- 2025P011192
- Acronym
- MOTIVATE
- Status last verified
- Sep 2026
- First submitted
- 12 Jul 2019
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34589194
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MOdern Treatment of Inhibitor-PositiVe PATiEnts With Haemophilia A - An International Observational Study
- ClinicalTrials.gov ID
- NCT04023019
- Acronym / sponsor ID
- MOTIVATE / IRB00113316
- Conditions
- Hemophilia A
- Keywords
- Blood disorders
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Octapharma
- Study start
- 17 Mar 2020 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 17 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will capture different approaches in the management of persons with haemophilia A (HA) and inhibitors. HA is a serious blood coagulation disorder caused by a deficiency in FVIII that results in a failure to produce FVIII in sufficient quantities to achieve satisfactory haemostasis. Patients with HA are predisposed to recurrent bleeds into joints and soft tissues that culminate in debilitating arthropathy and long-term morbidity. HA can be effectively treated with replacement FVIII concentrates, obtained by fractionation of human plasma (pdFVIII) or using recombinant technology (rFVIII). In patients receiving FVIII replacement therapy, inhibitors can develop that neutralise the effect of treatment. Inhibitors develop in ~35% of patients who have not been previously exposed to FVIII treatment and ~1% of patients who have undergone previous FVIII treatment. Inhibitor development has major adverse implications on bleeding rates, morbidity, mortality and quality of life.
Immune tolerance induction (ITI), which involves prolonged treatment with plasma-derived (pdFVIII) or recombinant FVIII (rFVIII), is the only clinically proven strategy for eradication of inhibitors and is recommended as the primary treatment option in European and US guidelines. Bypassing agents (activated recombinant factor VII [rFVIIa] and activated prothrombin complex concentrate [aPCC]) are used to manage bleeding episodes (BEs) and for prophylaxis or in surgical settings in patients with FVIII inhibitors. The bispecific factor IX (FIX) and factor X (FX) monoclonal antibody emicizumab was approved in the US in November 2017, and in Europe in February 2018.
The overall objective of this study is to capture different approaches in the management of participants with HA and inhibitors, document current ITI approaches, and evaluate efficacy and safety of ITI, including the combination of FVIII and emicizumab. Patients will be assigned to 1 of 3 groups based on the treatments they receive:
- Group 1 receives ITI with Nuwiq, octanate, or wilate, with aPCC or rFVIIa administered as needed
- Group 2 receives ITI with Nuwiq, octanate, or wilate, in combination with emicizumab, with aPCC or rFVIIa administered as needed
- Group 3 receives routine prophylaxis with emicizumab, aPCC or rFVIIa without ITI
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: ITI with Nuwiq, octanate, or wilate | – | Biological: Nuwiq, Biological: Octanate, Biological: Wilate, Biological: Recombinant factor VIIa (rFVIIa), Biological: Activated prothrombin complex concentrate (aPCC)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 | – | Biological: Nuwiq, Biological: Octanate, Biological: Wilate, Biological: Emicizumab, Biological: Recombinant factor VIIa (rFVIIa), Biological: Activated prothrombin complex concentrate (aPCC)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 | – | Biological: Emicizumab, Biological: Recombinant factor VIIa (rFVIIa), Biological: Activated prothrombin complex concentrate (aPCC)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. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NuwiqNuwiq 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. | Biological | Group 1: ITI with Nuwiq, octanate, or wilate, Group 2: ITI with Nuwiq, octanate, or wilate with emicizumab |
| OctanateOctanate 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. | Biological | Group 1: ITI with Nuwiq, octanate, or wilate, Group 2: ITI with Nuwiq, octanate, or wilate with emicizumab |
| WilateWilate 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. | Biological | Group 1: ITI with Nuwiq, octanate, or wilate, Group 2: ITI with Nuwiq, octanate, or wilate with emicizumab |
| EmicizumabAlso: HemlibraEmicizumab 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. | Biological | Group 2: ITI with Nuwiq, octanate, or wilate with emicizumab, Group 3: Prophylaxis with emicizumab, aPCC, or rFVIIa |
| Recombinant factor VIIa (rFVIIa)Also: NovoSevenRecombinant 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. | Biological | Group 1: ITI with Nuwiq, octanate, or wilate, Group 2: ITI with Nuwiq, octanate, or wilate with emicizumab, Group 3: Prophylaxis with emicizumab, aPCC, or rFVIIa |
| Activated prothrombin complex concentrate (aPCC)Also: FEIBAActivated 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. | Biological | Group 1: ITI with Nuwiq, octanate, or wilate, Group 2: ITI with Nuwiq, octanate, or wilate with emicizumab, Group 3: Prophylaxis with emicizumab, aPCC, or rFVIIa |
Primary outcome
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
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.
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
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.
Proportion of participants achieving FVIII half-life ≥ 6 h (Groups 1 and 2)
Time frame: Up to 5 years
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.
Annualized bleeding rate
Time frame: Up to 5 years
Annualized rate of all bleeding episodes will be reported and compared between all 3 study groups.
11 secondary outcomes
Time to achieve immune tolerance induction outcome
Time frame: Up to 5 years
Frequency of emicizumab, aPCC, and rFVIIa use during immune tolerance induction
Time frame: Up to 5 years
Rate of FVIII inhibitor relapse
Time frame: Up to 5 years
Frequency of bleeding episodes
Time frame: Up to 5 years
Severity of bleeding episodes
Time frame: Up to 5 years
Number of infusions required to control bleeding episodes
Time frame: Up to 5 years
Frequency of bleeding with surgical procedures
Time frame: Up to 5 years
Severity of bleeding with surgical procedures
Time frame: Up to 5 years
Proportion of participants experiencing adverse drug reactions
Time frame: Up to 5 years
Number of thrombotic events
Time frame: Up to 5 years
Treatment costs
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Derived from this study: PubMed 34589194Escuriola 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robert Sidonio, MD, MSc principal investigator
Emory University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophilia A, run by Emory University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Robert Sidonio, MD, MSc (404-785-1637, robert.sidonio.jr@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04023019, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.