Atypical Hemolytic Uremic Syndrome
Conditions
Keywords
Atypical Hemolytic Uremic Syndrome, aHUS,, thrombotic microangiopathy, TMA
Brief summary
The purpose of this Phase 3 study is to evaluate the efficacy and safety of iptacopan upon switching from anti-C5 antibody to iptacopan treatment in study participants with aHUS.
Detailed description
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.
Interventions
DRUGIptacopan
Open Label
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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: 1. Hematological normalization in platelet count ≥150 x 10\^9/L and LDH below upper limit of normal \[ULN\], and 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants free of TMA manifestation | 12 months | Absence of thrombotic microangiopathy (TMA) manifestation, without use of anti-C5 antibody, during the 12 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants free of TMA manifestation in study participants with functionally significant mutations in complement genes or positive anti FH antibodies | 12 months, 24 months | Absence of thrombotic microangiopathy (TMA) manifestation in study participants with functionally significant mutations in complement genes or positive anti FH antibodies, without the use of anti-C5 antibody during iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment. |
| Percentage of participants free of TMA manifestation | 24 months | Absence of thrombotic microangiopathy (TMA) manifestation, without use of anti-C5 antibody, during the 24 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment. |
| Time to TMA manifestation | 12 months, 24 months | Time to thrombotic microangiopathy (TMA) manifestation |
| Change from baseline in platelets | Baseline, month 12, month 24 | Change from baseline in platelets at month 12 and month 24. |
| Change from baseline in LDH | Baseline, month 12, month 24 | Change from baseline in lactate dehydrogenase (LDH) at month 12 and month 24. |
| Change from baseline in hemoglobin | Baseline, month 12, month 24 | Change from baseline in hemoglobin at month 12 and month 24. |
| Change from baseline in serum creatinine | Baseline, month 12, month 24 | Change from baseline in serum creatinine at month 12 and month 24. |
| Change from baseline in UPCR | Baseline, month 12, month 24 | Change from baseline in urine protein to creatinine ratio (UPCR) at month 12 and month 24. |
| Change from baseline in eGFR | Baseline, month 12, month 24 | Change from baseline in estimated glomerular filtration rate (eGFR) at month 12 and month 24. |
| Change from baseline in CKD stage | Baseline, month 12, month 24 | Change from baseline in chronic kidney disease (CKD) stage at month 12 and month 24. |
| Number of participants who require dialysis | month 12 and month 24 | Dialysis requirement status (Yes/ No) |
| Percentage of participants with TMA related events. | month 12 and month 24 | Percentage of participants with thrombotic microangiopathy (TMA) related events. |
Countries
China, France, Germany, Italy, Japan, Spain, Turkey (Türkiye), United Kingdom
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed