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

Novartis Pharmaceuticals33 sites in 8 countries50 target enrollmentFebruary 28, 2024

ConditionsAtypical Hemolytic Uremic Syndrome

InterventionsIptacopan

DrugsIptacopan

Overview

Phase: Phase 3
Intervention: Iptacopan
Conditions: Atypical Hemolytic Uremic Syndrome
Sponsor: Novartis Pharmaceuticals
Enrollment: 50
Locations: 33
Primary Endpoint: Percentage of participants free of TMA manifestation
Status: Recruiting
Last Updated: 3 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 28, 2024

End Date

July 19, 2029

Last Updated

3 days ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility 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 (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:
•Hematological normalization in platelet count ≥150 x 10\^9/L and LDH below upper limit of normal \[ULN\], and
•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

Arms & Interventions

iptacopan 200 mg b.i.d.

open label arm of iptacopan 200 mg b.i.d.

Intervention: Iptacopan

Outcomes

Primary Outcomes

Percentage of participants free of TMA manifestation

Time Frame: 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 Outcomes

Time to TMA manifestation(12 months, 24 months)
Percentage of participants with TMA related events.(month 12 and month 24)
Number of participants who require dialysis(month 12 and month 24)
Change from baseline in platelets(Baseline, month 12, month 24)
Change from baseline in UPCR(Baseline, month 12, month 24)
Change from baseline in eGFR(Baseline, month 12, month 24)
Percentage of participants free of TMA manifestation(24 months)
Change from baseline in LDH(Baseline, month 12, month 24)
Change from baseline in serum creatinine(Baseline, month 12, month 24)
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)
Change from baseline in hemoglobin(Baseline, month 12, month 24)
Change from baseline in CKD stage(Baseline, month 12, month 24)