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

Atypical Hemolytic Uremic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05935215
• Other study ID #: CLNP023F12302
• Status: Recruiting
• Phase: Phase 3
• Start date: February 28, 2024
• Est. completion date: July 21, 2029

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 21, 2029
• Est. primary completion date: January 25, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. Hematological normalization in platelet count =150 x 109/L and LDH below upper limit of normal [ULN], and

2. 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

Related Conditions & MeSH terms

• Atypical Hemolytic Uremic Syndrome
• Azotemia
• Hemolysis
• Hemolytic-Uremic Syndrome
• Syndrome

Intervention

Drug:
• Iptacopan
Open Label

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Iruma-gun	Saitama
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Mersin

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Japan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Time to TMA manifestation	Time to thrombotic microangiopathy (TMA) manifestation	12 months, 24 months
Secondary	Change from baseline in platelets	Change from baseline in platelets at month 12 and month 24.	Baseline, month 12, month 24
Secondary	Change from baseline in LDH	Change from baseline in lactate dehydrogenase (LDH) at month 12 and month 24.	Baseline, month 12, month 24
Secondary	Change from baseline in hemoglobin	Change from baseline in hemoglobin at month 12 and month 24.	Baseline, month 12, month 24
Secondary	Change from baseline in serum creatinine	Change from baseline in serum creatinine at month 12 and month 24.	Baseline, month 12, month 24
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of participants who require dialysis	Dialysis requirement status (Yes/ No)	month 12 and month 24
Secondary	Percentage of participants with TMA related events.	Percentage of participants with thrombotic microangiopathy (TMA) related events.	month 12 and month 24