Adakveo (crizanlizumab-tmca)

P3, N=315, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P=N/A, N=376, Completed, Novartis

P2, N=117, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P1/2, N=45, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P3, N=315, Not yet recruiting, Novartis Pharmaceuticals

P2, N=119, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2026 --> Jan 2025

P4, N=3239, Active, not recruiting, Matthew Neal MD | N=880 --> 3239

P4, N=140, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P1/2, N=45, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2024 --> Jul 2024

P2, N=119, Recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2026 --> Jun 2026 | Trial primary completion date: May 2024 --> Jan 2025

P=N/A, N=44, Terminated, Novartis Pharmaceuticals | N=320 --> 44 | Trial completion date: Jan 2025 --> Aug 2023 | Recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Aug 2023; sponsor decision

P2, N=36, Completed, Novartis Pharmaceuticals | Recruiting --> Completed | N=56 --> 36

Inclacumab is able not only to prevent the adhesion of RBCs to acutely and chronically activated HUVECs but is able to remove the preexisting adhesion and results in significant higher reduction compared to untreated. RBCs adhesion assay on Endothelium-on-a-chip is a novel and efficient way to study the efficacy of the new antiadhesive drug and could be used to monitor patient response to new therapies in SCD. Figure1: Effect of Inclacumab vs Crizanlizumab on removal of SCD RBC adhesion to heme activated HUVECs.

P2, N=33, Recruiting, Sheba Medical Center | Not yet recruiting --> Recruiting

Continuous vaso-occlusive (VO) and inflammatory processes in the vasculature are most likely the principal cause of such lesions, and there is little evidence, to date, that long-term hydroxyurea therapy (the standard of care for SCD) reduces organ damage in SCD adults. Inhibition of P-selectin activity, using crizanlizumab, has shown some success for reducing VO crisis frequency in SCD. Furthermore, interleukin (IL)-1β blockade, in the form of canakinumab administration, was well tolerated in young patients with SCD and associated with inflammatory marker reduction...Combination treatments, however, especially in the kidney and liver, had more complex effects. We suggest that future preclinical and clinical studies should investigate the potential of anti-inflammatory/adhesion approaches (alone or in combination) for preventing damage to multiple organs, in addition to preventing VO events.

P4, N=880, Active, not recruiting, Matthew Neal MD | Trial completion date: Nov 2023 --> Jun 2024

P2, N=33, Not yet recruiting, Sheba Medical Center

Methods ADORE (NCT04097821) is a 3-part, open-label, multicenter, phase 1/2, platform study that will assess the safety and efficacy of RUX in combination with 5 novel compounds for the treatment of MF: siremadlin (HDM2 inhibitor), crizanlizumab (anti-P-selectin antibody), sabatolimab (anti-TIM-3 antibody), rineterkib (ERK1/2 inhibitor) and NIS793 (anti-TGFβ antibody) ( Figure ). Assuming all five combination treatments enter Part 2 and one combination treatment is expanded in Part 3, a total of 240 patients are planned to be enrolled. The study is open for enrolling into Part 1.

METHODS ADORE (NCT04097821) is a 3-part, open-label, multicenter, Phase 1/2 open-platform study that will assess the safety and efficacy of RUX in combination with ≥ 3 novel compounds (siremadlin [HDM2 inhibitor], crizanlizumab [P-selectin inhibitor], or sabatolimab [TIM-3 inhibitor]) for the treatment of MF (Figure). Planned enrollment for the study with the current 3 combinations is 130 pts. Enrollment is currently ongoing.