Abstract Number: PB0503
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Explorer4 (NCT03196284) was a phase 2 trial to establish clinical proof-of-concept for subcutaneous, once-daily concizumab (anti-tissue factor pathway inhibitor [TFPI] monoclonal antibody) in bleed prevention in hemophilia A/B with inhibitors (HAwI/HBwI).
Aims: Assess safety and efficacy in patients who switched from recombinant activated FVII (rFVIIa) on-demand treatment in the explorer4 main part to daily concizumab prophylaxis in the extension.
Methods: Patients, randomized 2:1, received daily concizumab prophylaxis/rFVIIa on-demand during the explorer4 main part (≥24 weeks). During the extension (56–94 weeks), on-demand patients switched to 0.15 mg/kg concizumab prophylaxis (following a loading dose of 0.5 mg/kg), with the possibility to escalate to 0.20 and 0.25 mg/kg (if ≥3 spontaneous treated bleeds occurred within 12 weeks). Annualized bleeding rate (ABR) was estimated based on a negative binomial regression with log-exposure time as offset and treatment arm as a factor. Results are presented at the last concizumab dose level.
Results: Eight patients (6 HAwI; 2 HBwI) were included in this sub-analysis. Two patients remained on 0.15 mg/kg concizumab; 3 escalated to 0.20 mg/kg and 3 to 0.25 mg/kg. One patient fulfilled protocol-defined lack of efficacy criteria on 0.25 mg/kg and was withdrawn. Estimated mean ABR (95% confidence interval [CI]) was 19.2 (10.7; 34.2) vs 4.9 (2.4; 10.0) for on-demand treatment and concizumab prophylaxis, respectively. Estimated mean spontaneous and joint bleed ABR (95% CI) decreased from 17.0 (9.7; 29.8) to 2.5 (1.1; 5.7), and from 14.8 (8.1; 26.9) to 3.0 (1.3; 6.9), respectively. Three patients experienced zero bleeds on their last concizumab dose level (exposure time: 212, 115, 303 days). There were no safety signals following concizumab switching.
Conclusions: Safety and efficacy for explorer4 patients who switched from rFVIIa on-demand to concizumab prophylaxis were consistent with main/extension part trial results, with longer-term efficacy maintained and a favorable safety profile while on concizumab.
To cite this abstract in AMA style:
Shapiro A, Cepo K, Tønder SM, Young G, Jiménez-Yuste V. Safety and Efficacy of Concizumab Prophylaxis Following a Switch from rFVIIa on-demand Treatment: Sub-analysis Results from the Phase 2 Explorer4 Trial in Patients with Hemophilia A or B with Inhibitors [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/safety-and-efficacy-of-concizumab-prophylaxis-following-a-switch-from-rfviia-on-demand-treatment-sub-analysis-results-from-the-phase-2-explorer4-trial-in-patients-with-hemophilia-a-or-b-with-inhibito/. Accessed March 22, 2024.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/safety-and-efficacy-of-concizumab-prophylaxis-following-a-switch-from-rfviia-on-demand-treatment-sub-analysis-results-from-the-phase-2-explorer4-trial-in-patients-with-hemophilia-a-or-b-with-inhibito/