Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)

The study is designed as a multicenter, single-arm, open label study to evaluate the efficacy and safety of iptacopan upon switching from anti-C5 antibody to iptacopan treatment in participants with aHUS. It consists of a screening period of up to 14 weeks followed by a 12-Month Core Treatment period and 12-Month Extension Treatment period.

The study will assess the effects of iptacopan on a range of efficacy assessments relevant to aHUS.

Inclusion criteria

• Male and female adult participants ≥ 18 years of age with diagnosis of aHUS for whom etiologies of other types of TMA and non-aHUS kidney disease have been excluded.

•. Currently on the recommended (as per label) dosage regimen of anti-C5 antibody treatment, for at least 3 months prior to entering the screening period.

• In the opinion of the investigator the participant has responded to anti-C5 antibodytreatment prior to screening and has clinical evidence of response (in absence of PE/PI) during the Screening period.

Clinical evidence of response to anti-C5 antibody treatment (in absence of PE/PI) confirmed during the Screening period by central laboratory at two visits 12 weeks apart. Clinical evidence of response is defined as:

• Hematological normalization in platelet count ≥150 x 10^9/L and LDH below upper limit of normal [ULN], and
• Stable kidney function as defined by serum creatinine values within ±15% during the Screening period

• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections is required prior to the start of treatment with iptacopan.
• If not received previously or if a booster is required, vaccination against Haemophilus influenzae infection, should be given, if available and according to local regulations.

Exclusion criteria

• History of aHUS disease relapse while on anti-C5 antibody treatment.
• eGFR < 30 ml/min/1.73m^2
• Active infection or history of recurrent invasive infections caused by encapsulated bacteria, i.e., meningococcus, pneumococcus (eg., N. meningitidis, S. pneumoniae) or H. influenzae.
• Participants with sepsis or active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study treatment administration.
• Kidney, bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT), heart, lung, small bowel, pancreas, liver transplantation or any other cell or solid organ transplantation
• Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study
• Any medical condition deemed likely to interfere with the patient's participation in the study