Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: iptacopan 200 mg b.i.d. open label arm of iptacopan 200 mg b.i.d. |
Drug: Iptacopan
Open Label
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
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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
- influenzae.
-
Participants with sepsis or active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study treatment administration.
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CLNP023F12302