Various Treatments for Hemophilia A

(MOTIVATE Trial)

Recruiting at 3 trial locations

Overseen By Carmen Escuriola-Ettingshausen, MD

Age: Any Age

Sex: Male

Trial Phase: Academic

Sponsor: Emory University

Must be taking: Nuwiq, Octanate, Wilate, Emicizumab

Disqualifiers: Other coagulation disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the best ways to manage hemophilia A in men who have developed inhibitors (resistance) to factor VIII treatments. The study observes how different treatment approaches, including immune tolerance induction (ITI) and the use of emicizumab (a bispecific antibody), perform in real-life settings. Participants are grouped based on their treatment plans, which may include various combinations of medications to prevent or control bleeding. This trial suits men with hemophilia A who have a history of developing inhibitors and have previously tried ITI. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to advancing treatment options.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It seems to focus on observing current treatments, so you might be able to continue your existing medications, but it's best to confirm with the trial organizers.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments studied for hemophilia A with inhibitors are generally well-tolerated. For Emicizumab, studies indicate it is well-tolerated, with mild injection site reactions as the most common issue. No serious blood clotting problems appeared in these studies.

Activated prothrombin complex concentrate (aPCC) effectively controls bleeding without major safety concerns when used at recommended doses, especially in combination with Emicizumab.

Recombinant factor VIIa (rFVIIa) has a good safety record, with no unexpected safety issues reported. However, higher doses can increase the risk of certain blood clots.

Nuwiq, Octanate, and Wilate have all undergone safety studies for hemophilia treatment. Nuwiq is generally safe but can rarely cause allergic reactions. Wilate, derived from human blood, carries a small theoretical risk of virus transmission, though this hasn't been a real-world issue. Specific safety details for Octanate weren't provided, but it is used similarly to other factor VIII products.

Overall, these treatments have demonstrated safety in previous use, but monitoring for any side effects during treatment remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for Hemophilia A with FVIII inhibitors because they offer new ways to manage bleeding episodes. Unlike standard treatments that often involve frequent infusions of clotting factors, emicizumab provides a more convenient prophylactic option that mimics the action of factor VIII, reducing the frequency of bleeding episodes with less frequent dosing. Additionally, the use of immune tolerance induction (ITI) strategies with Nuwiq, Octanate, or Wilate, in combination with emicizumab, aims to eliminate inhibitors and restore the effectiveness of standard factor VIII treatments. This approach could potentially offer a more comprehensive solution for patients struggling with inhibitors, which is a significant challenge in Hemophilia A management.

What evidence suggests that this trial's treatments could be effective for managing haemophilia A with FVIII inhibitors?

Research has shown that several treatments hold promise for hemophilia A patients with factor VIII inhibitors. In this trial, participants in Group 1 will receive immune tolerance induction (ITI) with either Nuwiq, octanate, or wilate. Nuwiq has effectively treated unexpected bleeding, with 83% of cases rated as excellent or good. Octanate has successfully reduced inhibitors and proved very effective in ITI therapy. Wilate has helped prevent bleeding, significantly lowering the rate of spontaneous bleeds.

Participants in Group 2 will receive ITI with Nuwiq, octanate, or wilate combined with emicizumab prophylaxis. Emicizumab has reduced bleeding events by 72%, with many patients experiencing no bleeds requiring treatment.

Group 3 will receive routine prophylaxis with emicizumab, aPCC, or rFVIIa without ITI. Activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa) have both effectively treated bleeding episodes, with rFVIIa showing a positive response in up to 91% of cases. These treatments offer various ways to manage hemophilia A with inhibitors, aiming to reduce bleeding and improve quality of life. ^{2 6 7 8 9}

Who Is on the Research Team?

Robert Sidonio, MD, MSc

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 wilate and/or 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 study documents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune tolerance induction (ITI) with FVIII products and/or emicizumab, with aPCC or rFVIIa administered as needed

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including inhibitor titer and bleeding episodes

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Activated prothrombin complex concentrate (aPCC)
• Emicizumab
• Nuwiq
• Octanate
• Recombinant factor VIIa (rFVIIa)
• Wilate

How Is the Trial Designed?

Group I: Group 3: Prophylaxis with emicizumab, aPCC, or rFVIIa Experimental Treatment 3 Interventions

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.

Group II: Group 2: ITI with Nuwiq, octanate, or wilate with emicizumab Experimental Treatment 6 Interventions

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 III: Group 1: ITI with Nuwiq, octanate, or wilate Experimental Treatment 5 Interventions

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.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Octapharma

Industry Sponsor

Trials

86

Recruited

11,300+

Wolfgang Marguerre

Octapharma

Chief Executive Officer since 1983

MBA from INSEAD

Wolfgang Frenzel

Octapharma

Chief Medical Officer since 2010

MD from University of Vienna

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4935538/

Global Post-Authorization Safety Surveillance Study Eighty-one patients were treated with FEIBA at 40 sites in 10 countries over a 4-year period. Sixty-nine patients (85.2%) had hemophilia A, two had (2.5%) ...

2. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/2418/423060/Real-World-Clinical-Management-of-Patients-with

Effectiveness and Safety of aPCC in Patients with >18 Months ... The primary objective of the FEIBA Global Outcome study (FEIBA GO) is to describe the long-term, real-world effectiveness and safety of activated prothrombin ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S247503792500250X

Activated prothrombin complex concentrate in patients ... In a pooled analysis of data from the HAVEN 1-4 trials, 130 bleeds in 37 people with hemophilia A with inhibitors receiving emicizumab prophylaxis were treated ...

4. rarediseaseadvisor.com rarediseaseadvisor.com/news/activated-prothrombin-complex-concentrate-hemostatic-agent-hemophilia-a/

Evaluating aPCC as a Hemostatic Agent in Hemophilia A Approximately 50% of hemorrhages were treated with aPCC. It was used as initial therapy on 14 occasions and resolved the bleeding in 13 of them.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19335751/

Efficacy of recombinant activated factor VII vs. ... In comparison, a typical regimen of 75 IU kg(-1) aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3875259/

Activated Prothrombin Complex Concentrates for the ... The theoretical risks of thrombosis associated with PCC products must be carefully considered before they are administered to patients who require coagulation ...

7. nature.com nature.com/articles/s41598-022-05803-w

Efficacy and safety of activated prothrombin complex ... This study suggests that the use of aPCCs is effective in achieving effective hemostasis in patients on warfarin presenting with major bleeding.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36029160/

Activated prothrombin complex concentrate to treat ... This data support aPCC as hemostatic treatment in AHA with high effectiveness and excellent safety profile in acute bleeds and as extended use to prevent ...

9. journals.lww.com journals.lww.com/ccmjournal/fulltext/2020/01001/947__fixed_dose_activated_prothrombin_complex.908.aspx

947: fixed-dose activated prothrombin complex concentrate ... Efficacy was assessed in patients who presented with bleeding. Safety was assessed in all patients. The primary outcome was achievement of effective hemostasis.