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

Study Overview
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Brief Summary
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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
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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 8 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.

Official Title
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A Multicenter, Single Arm, Open-label Study to Evaluate Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With aHUS

Conditions
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Atypical Hemolytic Uremic Syndrome

Intervention / Treatment
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* Drug: Iptacopan


Participation Criteria
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Eligibility Criteria
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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 weight-based dosage regimen of anti-C5 antibody treatment for at least 3 months prior to the screening visit. Clinical evidence of response to anti-C5 antibody treatment (in absence of PE/PI) for at least 3 months prior to entering the screening period as defined by: Hematological normalization in platelet count ≥150 x 109/L and LDH below upper limit of normal [ULN], and Stable or improving kidney function as defined by ≤15% increase in serum creatinine. 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iptacopan 200 mg b.i.d.<br>open label arm of iptacopan 200 mg b.i.d. | Drug: Iptacopan<br>* Open Label<br>* Other names: LNP023;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants free of TMA manifestation | 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. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants free of TMA manifestation in study participants with functionally significant mutations in complement genes or positive anti FH antibodies | 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. | 12 months, 24 months | 
| Percentage of participants free of TMA manifestation | 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. | 24 months | 
| Time to TMA manifestation | Time to thrombotic microangiopathy (TMA) manifestation | 12 months, 24 months | 
| Change from baseline in platelets | Change from baseline in platelets at month 12 and month 24. | Baseline, month 12, month 24 | 
| Change from baseline in LDH | Change from baseline in lactate dehydrogenase (LDH) at month 12 and month 24. | Baseline, month 12, month 24 | 
| Change from baseline in hemoglobin | Change from baseline in hemoglobin at month 12 and month 24. | Baseline, month 12, month 24 | 
| Change from baseline in serum creatinine | Change from baseline in serum creatinine at month 12 and month 24. | Baseline, month 12, month 24 | 
| Change from baseline in UPCR | Change from baseline in urine protein to creatinine ratio (UPCR) at month 12 and month 24. | Baseline, month 12, month 24 | 
| Change from baseline in eGFR | Change from baseline in estimated glomerular filtration rate (eGFR) at month 12 and month 24. | Baseline, month 12, month 24 | 
| Change from baseline in CKD stage | Change from baseline in chronic kidney disease (CKD) stage at month 12 and month 24. | Baseline, month 12, month 24 | 
| Number of participants who require dialysis | Dialysis requirement status (Yes/ No) | month 12 and month 24 | 
| Percentage of participants with TMA related events. | Percentage of participants with thrombotic microangiopathy (TMA) related events. | month 12 and month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atypical Hemolytic Uremic Syndrome, aHUS, thrombotic microangiopathy, TMA