Haemophilic Pseudotumour Clinical Trial
Official title:
Prospective, Single-arm, Open-label Use of Hemlibra (Emicizumab) to Treat Hemophilic Pseudotumor
| Verified date | March 2024 |
| Source | Indiana Hemophilia &Thrombosis Center, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a single arm, phase 4, prospective, open-label, United States single-center study to assess the hemostatic efficacy and safety of Hemlibra (emicizumab) for hemostatic control of hemophilia A patients (baseline FVIII level <40%) with and without inhibitors with hemophilic pseudotumors; secondary outcomes will assess changes in quality of life and activity level in treated patients.
| Status | Terminated |
| Enrollment | 1 |
| Est. completion date | March 16, 2022 |
| Est. primary completion date | March 16, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A and older |
| Eligibility | Inclusion Criteria: - Signed informed consent form from the subject, parent or guardian - Diagnosis of congenital hemophilia A (baseline FVIII level <40%) with or without FVIII inhibitor, either high or low responding, regardless of titer - Diagnosis of a hemophilic pseudotumor confirmed by radiologic assessment such as CT or MRI - Any weight or BMI - Medical documentation of prophylactic or episodic treatment (FVIII or bypassing agent) and the number of bleeding episodes for at least 16 weeks, and up to 6 months if available, prior to entry into the study - Medical documentation of any need for PRBC transfusion or hospitalization for 6 months prior to entry into the study - Subjects with a history of an inhibitor should provide documentation of the inhibitor history including date of initial diagnosis of inhibitor, peak titer, and agent utilized for hemostatic control - Subjects with high titer inhibitors or those with low titer inhibitors who do not respond to FVIII must be willing to use rFVIIa as first line therapy for the treatment of breakthrough bleeding events - Medical documentation of ITI therapy for subjects with a history of a FVIII inhibitor and ITI, including current FVIII inhibitor titer - Willingness to discontinue any current prophylactic hemostatic regimen (FVIII or bypassing agent) and/or FVIII ITI therapy for the duration of the study - Subjects receiving FVIII prophylaxis must be willing to discontinue their FVIII prophylactic regimen immediately prior to their second loading dose of Hemlibra (emicizumab) - Subjects receiving bypassing agent prophylaxis must be willing to discontinue their prophylactic regimen at least 24 hours prior to their first loading dose of Hemlibra (emicizumab) - Subjects receiving FVIII ITI therapy must be willing to discontinue ITI immediately prior to their first loading dose of Hemlibra (emicizumab) - Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the health-related questionnaires, activity tracking, and bleed diaries, using systems provided during the study - Adequate hepatic function, defined as total bilirubin =1.5 × age-adapted upper limit of normal (ULN) (excluding Gilbert's syndrome) and both AST and ALT =3 × age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis - Subjects must be willing to be vaccinated against HAV and HBV if not previously vaccinated, exposed or immune to HAV or HBV* - Adequate hematologic function, defined as a platelet count =100,000/µL and a PT=1.5 times the ULN at the time of screening - Adequate renal function, defined as serum creatinine =2.5 × age-adapted ULN and creatinine clearance =30 mL/min by Cockcroft-Gault formula - For women with hemophilia of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 5 elimination half-lives (24 weeks) after the last dose of study drug Exclusion Criteria: - Inherited or acquired bleeding disorder other than congenital hemophilia A - Lack of a documented diagnosis of hemophilic pseudotumor - Patients who are at high risk for TMA (eg, have a previous medical or family history of TMA), in the Study Investigator's judgment - History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the Study Investigator's judgment - Previous (within the last 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease - Other conditions (eg, certain autoimmune diseases) that may currently increase the risk of bleeding or thrombosis - History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the Emicizumab injection - Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study - Known HIV infection with CD4 counts <200 cells/µL. HIV infection with CD4 counts =200 cells/µL permitted - Use of systemic immunomodulators (eg, interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy - Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the Study Investigator, pose an additional unacceptable risk in administering study drug to the patient - Receipt of any of the following: - Hemlibra (emicizumab) in a prior investigational study - An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration - A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter - Any other investigational drug currently being administered or planned to be administered - Inability to comply with the study protocol in the opinion of the Study Investigator - Pregnancy or lactation or intention to become pregnant during the study - Women with a positive serum pregnancy test result within 10 days prior to initiation of study drug |
| Country | Name | City | State |
|---|---|---|---|
| United States | Indiana Hemophila @Thrombosis Center | Indianapolis | Indiana |
| Lead Sponsor | Collaborator |
|---|---|
| Indiana Hemophilia &Thrombosis Center, Inc. | Genentech, Inc. |
United States,
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Liu SS, White WL, Johnson PC, Gauntt C. Hemophilic pseudotumor of the spinal canal. Case report. J Neurosurg. 1988 Oct;69(4):624-7. doi: 10.3171/jns.1988.69.4.0624. — View Citation
Magallon M, Monteagudo J, Altisent C, Ibanez A, Rodriguez-Perez A, Riba J, Tusell J, Martin-Villar J. Hemophilic pseudotumor: multicenter experience over a 25-year period. Am J Hematol. 1994 Feb;45(2):103-8. doi: 10.1002/ajh.2830450202. — View Citation
Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophili — View Citation
van Ommeren JW, Mooren DW, Veth RP, Novakova IR, van de Kaa CA. Pseudotumor occurring in hemophilia. Arch Orthop Trauma Surg. 2000;120(7-8):476-8. doi: 10.1007/s004029900087. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Hemostatic Efficacy of Prophylactic Weekly Injections of Hemlibra (Emicizumab) Based on Hemoglobin | Maintenance or increase of hemoglobin (g/dl) from participants' baseline level based on serial blood tests. | Every 6 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Primary | Hemostatic Efficacy of Prophylactic Weekly Injections of Hemlibra (Emicizumab) Based on Participants' Need for Blood Transfusions or Lack of | Whether or not the patient requires blood transfusions (units of RBCs) due to blood loss secondary to lack of hemostatic efficacy during the duration of study treatment duration. | Every 6 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Breakthrough Bleeds | Number of breakthrough bleeding events that require hemostatic therapy in addition to Hemlibra prophylaxis | Every 6 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Pseudotumor Status | Radiologic evaluation (CT and/or MRI) to evaluate control of progression, stabilization or regression per change in size (measured in cm) of the pseudotumor | Every 12 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Patient Quality of Life Based on Haem-A-QOL | The subjective change in quality of life and activity with Hemlibra (emicizumab) prophylaxis will be evaluated during the study. QoL and activity will be assessed using Haem-A-QoL and EQ-5D-5L. Changes in these measures will be determined by changes from the baseline scores compared to follow-up scores. | Every 12 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Patient Quality of Life Based on EQ-5D-5L | The subjective change in quality of life and activity with Hemlibra (emicizumab) prophylaxis will be evaluated during the study. QoL and activity will be assessed using Haem-A-QoL and EQ-5D-5L. Changes in these measures will be determined by changes from the baseline scores compared to follow-up scores. | Every 12 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Adverse Events | Number of adverse events while on HemLibra (emicizumab) prophylaxis. | Every 3 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Serious Adverse Events | Number of SAEs while on HemLibra (emicizumab) prophylaxis | Every 3 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Number of Participants With Adverse Events | Number of participants with adverse events while on HemLibra (emicizumab) prophylaxis | Every 3 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Anti-Drug Antibodies (ADA) | Development of emicizumab anti-drug antibodies using the ADA assay | Every 12 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | ADA and Activated Partial Thromboplastin Time (APTT) | If the patient develops an ADA: the ADA's effect on the patient's APTT | Every 12 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | ADA and Factor VIII (FVIII) | If the patient develops an ADA: the ADA's effecton the patient's FVIII assay | Every 12 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Planned or Unplanned Surgery | If the patient requires surgery: Whether the procedure(s) was/were planned versus unplanned | Every 6 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Hemostatic Agents in Surgery | If the patient requires surgery: Whether hemostatic agents in addition to Hemlibra were required to achieve or maintain hemostasis | Every 6 months, for the 2 years and 10 months of the patient's study participation duration. | |
| Secondary | Blood Loss in Surgery | If the patient requires surgery: Whether blood loss exceeded the estimated/predicted blood loss relative to a patient without hemophilia | Every 6 months, for the 2 years and 10 months of the patient's study participation duration. |