atypical hemolytic uremic syndrome MedDRA version: 20.1 Level: LLT Classification code 10079841 Term: Atypical hemolytic uremic syndrome System Organ Class: 100000004851
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult patients with evidence of thrombotic microangiopathy (TMA), including thrombocytopenia, evidence of hemolysis, and acute kidney injury - Vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections are required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations, at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination or before vaccination is given, prophylactic antibiotic treatment must be administered at the start of study treatment and for at least 2 weeks after vaccination Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: - Treatment with complement inhibitors, including anti-C5 antibody - ADAMTS13 deficiency (<5% activity), and/or Shiga toxin-related hemolytic uremic syndrome (STx-HUS), and/or Positive Coombs test - Identified drug exposure-related HUS or HUS related to known genetic defects of cobalamin C metabolism or known diacylglycerol kinase e (DGKE) mediated aHUS - Receiving PE/PI, for 28 days or longer, prior to the start of screening for the current TMA - Bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT), heart, lung, small bowel, pancreas, or liver transplantation - Patients with sepsis, severe systemic infection, COVID-19 infection, systemic infection which confounds an accurate diagnosis or aHUS or impedes the ability to manage the aHUS disease, active infection (or history of recurrent invasive infections) caused by encapsulated bacteria - Kidney disease suggestive of other disease than aHUS or of chronic kidney failure or family history of non-complement mediated genetic kidney disease - Liver disease or liver injury at screening - Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome - Chronic hemo- or peritoneal dialysis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): - The number/percentage of participants treated with iptacopan achieving complete thrombotic microangiopathy (TMA) response during 26 weeks of study treatment. Complete TMA Response is defined as (1) hematological normalization in platelet count (platelet count =150 x 10^9/L) and LDH (below ULN), and (2) improvement in kidney function (= 25% serum creatinine reduction from baseline), maintained for two measurements obtained at least four weeks apart, and any measurement in between - Long term (one year) safety, tolerability and efficacy of iptacopan via 1) safety evaluations including adverse events/serious adverse events, safety laboratory parameters, vital signs etc. after 52 weeks of study treatment, and 2) efficacy evaluations including complete TMA response, hematological parameters (platelets, LDH, hemoglobin), eGFR, PROs after 52 weeks of study treatment;Main Objective: - Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody - Long term safety and efficacy evaluations;Secondary Objective: - Time to achieve complete TMA response - Percentage of participants with increase from baseline in hemoglobin levels = 2 g/dL - Change from baseline in hematologic parameters - Percentage of participants on dialysis - Change from baseline on estimated glomerular filtration rate - Change from baseline in chronic kidney disease (CKD) stage - Change from baseline in patient-reported outcomes score ;Timepoint(s) of evaluation of this end point: - 26 weeks of study treatment - 52 weeks of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Effect of study treatment iptacopan on time to complete TMA response during the first 26 weeks of study treatment - Response is defined as the percentage of participants with an increase in hemoglobin of = 2g/dL from baseline, observed at two measurements obtained at least 4 weeks apart and any measurement in between during 26 weeks of study treatment - Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at week 26 - For participants requiring dialysis withing 5 days prior to iptacopan treatment initiation, the number of participants who no longer require dialysis through 26 weeks of study treatment will be evaluated by means of proportion and corresponding confidence interval - Change from baseline in eGFR after 26 weeks of study treatment - Change from baseline in CDK stage (1-5) based on eGFR categories at week 26 - Change from baseline in patient-reported outcomes scores for FACIT-Fatigue, Patient Global Impression of Severity (PGIS), EuroQol 5-level EQ-5D version (EQ-5D-5L) and Short-form 36 health survey questionnaire version 2 (SF-36 v2) at week 26;Timepoint(s) of evaluation of this end point: - 26 weeks of study treatment - 26 weeks of study treatment - At week 26 - 26 weeks of study treatment - At week 26 - At week 26 - At week 26 | — |
Countries
Austria, Brazil, China, Czechia, Greece, Hungary, India, Japan, Korea, Republic of, Russian Federation, Slovenia, Taiwan, United Kingdom, United States
Contacts
Public ContactDrug Regulatory Affairs
Novartis Pharma GmbH
Outcome results
None listed