Background: Arthropathy caused by repeated joint bleeding is a major complication in patients with severe hemophilia A and is associated with long-term morbidity. Factor VIII (FVIII) prophylaxis has proven benefits for prevention of bleeding, including joint bleeding, in these patients. Alongside preservation of joint health, FVIII prophylaxis may preserve bone mineral density (BMD) and reduce the risk of fractures. Emicizumab is a bi-specific monoclonal antibody with no structural homology to FVIII and is approved for prophylaxis in hemophilia A patients. However, data on the long-term impact of emicizumab on joint and bone health are limited.
Aims: To assess the impact of long-term prophylaxis with simoctocog alfa (Nuwiq ®; a fourth generation recombinant FVIII) versus emicizumab on joint and bone health in people with hemophilia A.
Methods: PROVE is a multinational, prospective, two-arm, low-interventional study that will collect clinical data on joint and bone health in patients receiving prophylaxis with simoctocog alfa or emicizumab in routine clinical practice. Approximately 200 male participants (100 in each treatment arm) at least 12 years of age with severe hemophilia A (FVIII activity [FVIII:C] <1%) will be enrolled. Written, informed consent will be obtained from each patient or their legal representative.
The primary objective of the study is to evaluate the long-term effect of simoctocog alfa versus emicizumab on joint health as measured by magnetic resonance imaging (MRI). The primary endpoint will be a between-group comparison of the change in total score on the extended MRI (eMRI) scale (Table 1). Secondary and exploratory endpoints include the impact of simoctocog alfa vs emicizumab on bleeding rates, joint and bone health, physical activity, quality of life and safety (Table 1). Study treatments will be defined by the treating physician prior to inclusion of a patient into the study. Patients will not be randomized to the treatment groups but will continue with their current prophylactic regimen (simoctocog alfa or emicizumab). Patients will be provided with an electronic diary (eDiary) in which to record study related data, including treatment-related data, bleeding event details, fracture details, concomitant medications and adverse drug reactions. Each patient will be followed for up to 4 years. An interim analysis is planned after 2 years.
Conclusion: ThePROVE study aims to generate real-world data on the long-term effects of prophylaxis with simoctocog alfa or emicizumab on joint and bone health in hemophilia A.
Disclosures
Klamroth:Sanofi: Honoraria, Other: Advisory board; Roche/Chugai: Honoraria, Other: Advisory board; Pfizer: Honoraria, Other: Advisory board; Octapharma: Honoraria, Other: Advisory board; Novo Nordisk: Honoraria, Other: Advisory board; Grifols: Honoraria, Other: Advisory board; CSL Behring: Honoraria, Other: Advisory board; Biotest: Honoraria, Other: Advisory board; BioMarin: Honoraria, Other: Advisory board; Bayer: Honoraria, Other: Advisory board; Sobi: Honoraria, Other: Advisory board; Takeda: Honoraria, Other: Advisory board. Sidonio:Pfizer: Honoraria; UniQure: Honoraria; Spark: Honoraria; Biomarin: Honoraria; Novo Nordisk: Honoraria; Bayer: Honoraria; Guardian Therapeutics: Honoraria; Takeda: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Genentech: Honoraria, Research Funding. Dargaud:CSL Behring: Membership on an entity's Board of Directors or advisory committees, Other: Expert Board, Research Funding; Novo Nordisk: Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees, Other: Expert Board; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Expert Board; BioMarin: Membership on an entity's Board of Directors or advisory committees, Other: Expert Board; LFB: Membership on an entity's Board of Directors or advisory committees, Other: Expert Board, Research Funding. Jiménez-Yuste:CSL Behring: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; BioMarin: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding. Ljung:Sobi: Consultancy, Speakers Bureau; Octapharma: Consultancy; Novo Nordisk: Consultancy; Sanofi: Consultancy; Takeda: Consultancy. Young:Spark: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy; Sanofi Genzyme: Consultancy, Speakers Bureau; Genentech/Roche: Consultancy; Hema Biologics: Speakers Bureau; Hema Biologics/LFB: Consultancy; CSL Behring: Consultancy, Speakers Bureau; Takeda: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Viatris: Patents & Royalties. Chowdary:Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Apcintex: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees; Freeline: Membership on an entity's Board of Directors or advisory committees, Research Funding; NovoNordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Spark: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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