New drug aimed at saving lives after stem cell transplants

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Age ≥12 years at the time of ICF signature. 2. Previous recipient of autologous or allogeneic HSCT. 3. Persistent TA-TMA despite initial management of potential triggers (e.g., CNI/mTOR inhibitor reduction, infection or GVHD treatment), with TMA activity sustained for ≥72 hours post-intervention. 4. TA-TMA diagnosis, confirmed ≤14 days prior to or during screening by either biopsy-proven microthrombi or ≥4 of the following: (1) LDH \> ULN (2) Proteinuria (rUPCR ≥1 mg/mg) (3) Hypertension (age-adjusted) (4) New-onset thrombocytopenia (platelet decrease ≥50%, count ≤50,000/mm³, or transfusion-refractory) (5) New-onset anemia or increased transfusion need (6) Microangiopathy on blood smear (schistocytes ≥1%) or biopsy (7) Elevated terminal complement complex (C5b-9) 5. High-risk TMA features (per 2023 consensus), meeting ≥1 criterion: 1. LDH ≥2× ULN 2. Elevated sC5b-9 3. Proteinuria (rUPCR ≥1 mg/mg) 4. Multi-organ dysfunction syndrome (MODS) 5. Concurrent Grade II-IV acute GVHD 6. Active systemic infection 6. Able to receive oral medication. 7. Failure of first-line therapy (e.g., CNI/mTOR inhibitor adjustment, plasma exchange, rituximab, defibrotide), excluding prior complement inhibitors. 8\. Life expectancy \>8 weeks. 9. Required vaccination against encapsulated bacteria (meningococcal, pneumococcal) per local guidelines, administered ≥2 weeks prior to first dose. If vaccination is delayed, antimicrobial prophylaxis is required. 10\. For subjects unable to receive meningococcal vaccines, antibiotic prophylaxis must be continued throughout treatment and for 8 months post-last dose. 11\. For subjects of reproductive potential: agreement to use effective contraception and, for females, a negative pregnancy test at screening. 12\. Provision of signed informed consent and compliance with study procedures. Exclusion Criteria: 1. Known familial or acquired ADAMTS13 deficiency (activity \<5%). 2. Known Shiga toxin-associated HUS (positive Shiga toxin assay or culture). 3. Positive direct Coombs test with clinically significant immune-mediated hemolysis per investigator. 4. Clinically overt disseminated intravascular coagulation (DIC) according to ISTH criteria. 5. Bone marrow/graft failure. 6. Known HIV infection (confirmed by testing within 6 months prior to screening). 7. Active meningococcal disease. 8. Septic shock requiring vasopressor support within 7 days prior to enrollment. 9. Pregnant or breastfeeding. 10. Any concurrent or prior medical condition unrelated to TA-TMA that, in the opinion of the investigator or sponsor, could increase risk or confound study outcomes (e.g., significant cardiac, pulmonary, renal, endocrine, or hepatic disease). 11. All-cause respiratory failure requiring mechanical ventilation within 72 hours prior to enrollment. 12. Acute/chronic heart failure with left ventricular ejection fraction ≤40%. 13. Prior treatment with iptacopan, eculizumab, or other complement inhibitors within 60 days before first study dose. 14. Use of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to screening. 15. Recurrent primary malignancy or post-transplant lymphoproliferative disorder (PTLD).