HemLibra Prophylaxis in Patients With Hemophilic Pseudotumor

NCT03921294 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: RO-IIS-2018-10581
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Haemophilic Pseudotumour

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (13)

• Breakthrough Bleeds

  Every 6 months, for the 2 years and 10 months of the patient's study participation duration.

• Pseudotumor Status

  Every 12 months, for the 2 years and 10 months of the patient's study participation duration.

• Patient Quality of Life Based on Haem-A-QOL

  Every 12 months, for the 2 years and 10 months of the patient's study participation duration.

• Patient Quality of Life Based on EQ-5D-5L

  Every 12 months, for the 2 years and 10 months of the patient's study participation duration.

• Adverse Events

  Every 3 months, for the 2 years and 10 months of the patient's study participation duration.

Study Arms (1)

Single Arm

EXPERIMENTAL

Patients with hemophilic pseudotumor will be treated with prophylactic emicizumab and assessed for improvement.

Drug: Emicizumab

Interventions

Emicizumab DRUG

bispecific monoclonal antibody binding to activated Factor IX and Factor X

Also known as: HemLibra

Single Arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana Hemophilia &Thrombosis Center, Inc.: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Indiana Hemophila @Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

Related Publications (8)

• Ahlberg AK. On the natural history of hemophilic pseudotumor. J Bone Joint Surg Am. 1975 Dec;57(8):1133-6.

  PMID: 1202003 RESULT

• Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A; Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014 Nov;12(11):1935-9. doi: 10.1111/jth.12672. Epub 2014 Sep 3. No abstract available.

  PMID: 25059285 RESULT

• Franchini M, Mannucci PM. Hemophilia A in the third millennium. Blood Rev. 2013 Jul;27(4):179-84. doi: 10.1016/j.blre.2013.06.002. Epub 2013 Jun 28.

  PMID: 23815950 RESULT

• Gringeri A, Leissinger C, Cortesi PA, Jo H, Fusco F, Riva S, Antmen B, Berntorp E, Biasoli C, Carpenter S, Kavakli K, Morfini M, Negrier C, Rocino A, Schramm W, Windyga J, Zulfikar B, Mantovani LG. Health-related quality of life in patients with haemophilia and inhibitors on prophylaxis with anti-inhibitor complex concentrate: results from the Pro-FEIBA study. Haemophilia. 2013 Sep;19(5):736-43. doi: 10.1111/hae.12178. Epub 2013 Jun 4.

  PMID: 23731246 RESULT

• 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.

  PMID: 3418398 RESULT

• 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.

  PMID: 8141115 RESULT

• 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 hemophilia. Haemophilia. 2013 Jan;19(1):e1-47. doi: 10.1111/j.1365-2516.2012.02909.x. Epub 2012 Jul 6.

  PMID: 22776238 RESULT

• 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.

  PMID: 10968546 RESULT

Related Links

• What is Hemophilia?
• WFH Guidelines for the management of hemophilia
• WFH report on the annual global survey 2011
• WFH report on the annual global survey 2013
• WFH report on the annual global survey 2015

MeSH Terms

Interventions

emicizumab

Results Point of Contact

• Title: Kat Molitor
• Organization: Indiana Hemophilia & Thrombosis Center

kmolitor@ihtc.org

3178710011

Study Officials

• Amy D Shapiro, MD

  Indiana Hemophilia &Thrombosis Center, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Model Details: single arm prospective open-label single-center study

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 19, 2019
• Study Start: May 15, 2019
• Primary Completion: March 16, 2022
• Study Completion: March 16, 2022
• Last Updated: April 11, 2024
• Results First Posted: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: IPD and additional information on study methods will be made available starting 9 months after publication or conclusion of the study and ending 36 months following publication or study conclusion.
• Access Criteria: IPD and study information will be shared with investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary"), whose proposals are methodologically sound, and for purposes that are consistent with the aims of the underlying research. Proposals will be reviewed by the Principle Investigator, Dr. Amy Shapiro, and may be submitted to ashapiro@ihtc.org. Requestors will be required to sign a data access and use agreement.

Locations

US (1)