Clinical trial NCT05935215: Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Atypical Hemolytic Uremic Syndrome
Keywords: Atypical Hemolytic Uremic Syndrome
aHUS, thrombotic microangiopathy
TMA
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-07-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.

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 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

Primary outcomes:
measure: Percentage of participants free of TMA manifestation
timeFrame: 12 months
Secondary outcomes:
measure: Percentage of participants free of TMA manifestation in study participants with functionally significant mutations in complement genes or positive anti FH antibodies
timeFrame: 12 months, 24 months
measure: Percentage of participants free of TMA manifestation
timeFrame: 24 months
measure: Time to TMA manifestation
timeFrame: 12 months, 24 months
measure: Change from baseline in platelets
timeFrame: Baseline, month 12, month 24
measure: Change from baseline in LDH
timeFrame: Baseline, month 12, month 24
measure: Change from baseline in hemoglobin
timeFrame: Baseline, month 12, month 24
measure: Change from baseline in serum creatinine
timeFrame: Baseline, month 12, month 24
measure: Change from baseline in UPCR
timeFrame: Baseline, month 12, month 24
measure: Change from baseline in eGFR
timeFrame: Baseline, month 12, month 24
measure: Change from baseline in CKD stage
timeFrame: Baseline, month 12, month 24
measure: Number of participants who require dialysis
timeFrame: month 12 and month 24
measure: Percentage of participants with TMA related events.
timeFrame: month 12 and month 24
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Iruma-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Mersin
country: Turkey
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: