Clinical trial NCT04889430: Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
Official title: A Multicenter, Single-arm, Open Label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily LNP023 in Adult aHUS Patients Who Are Naive to Complement Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Atypical Hemolytic Uremic Syndrome
Keywords: LNP023
iptacopan
aHUS
atypical hemolytic uremic syndrome
thrombotic microangiopathy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-05-17
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 determine whether iptacopan (LNP023) is efficacious and safe for the treatment of aHUS in adult patients who are treatment naive to complement inhibitor therapy.

Detailed description: The study is designed as a multicenter, single-arm, open label study to demonstrate the efficacy and safety of LNP023 (iptacopan) at a dose of 200 mg b.i.d. in adult patients with aHUS who are treatment naive to complement inhibitor therapy (including anti-C5 antibody). The study will enroll approximately 50 participants and assess the effects of iptacopan on a range of efficacy assessments relevant to aHUS including hematological and kidney parameters, dialysis requirement, changes in chronic kidney disease (CKD) stage, as well as patient reported outcomes (PRO) for fatigue and quality of life.

Eligibility criteria: Main Inclusion Criteria:

* Adult patients with evidence of active thrombotic microangiopathy (TMA), including thrombocytopenia, evidence of hemolysis, and acute kidney injury
* Vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections are required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations, at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination or before vaccination is given, prophylactic antibiotic treatment must be administered at the start of study treatment and for at least 2 weeks after vaccination

Main Exclusion Criteria:

* Treatment with complement inhibitors, including anti-C5 antibody
* ADAMTS13 deficiency (\<10% activity or \<0.1U/ml), and/or Shiga toxin-related hemolytic uremic syndrome (STx-HUS), and/or Positive direct Coombs test
* Identified drug exposure-related HUS or HUS related to known genetic defects of cobalamin C metabolism or known diacylglycerol kinase ε (DGKE) mediated aHUS
* Receiving PE/PI, for 14 days or longer, prior to the start of screening for the current TMA
* Bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT), heart, lung, small bowel, pancreas, or liver transplantation
* Patients with sepsis or active severe systemic bacterial, viral (including COVID-19) or fungal infection, systemic infection which confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease, active infection (or history of recurrent invasive infections) caused by encapsulated bacteria
* Kidney disease suggestive of other disease than aHUS or of chronic kidney failure or family history of non-complement mediated genetic kidney disease
* Liver disease or liver injury at screening
* Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome
* Chronic hemo- or peritoneal dialysis

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody
timeFrame: 26 weeks of study treatment
measure: Long term safety and efficacy evaluations
timeFrame: 52 weeks of study treatment
Secondary outcomes:
measure: Time to achieve complete TMA response
timeFrame: 26 weeks of study treatment
measure: Percentage of participants with increase from baseline in hemoglobin levels ≥ 2 g/dL
timeFrame: 26 weeks of study treatment
measure: Change from baseline on hematologic parameters
timeFrame: At week 26
measure: Percentage of participants on dialysis
timeFrame: 26 weeks of study treatment
measure: Change from baseline on estimated glomerular filtration rate
timeFrame: At week 26
measure: Change from baseline in chronic kidney disease (CKD) stage
timeFrame: At week 26
measure: Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire
timeFrame: At week 26
measure: Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire
timeFrame: At Week 26
measure: Change from baseline in patient-reported outcomes score as measured by the Patient Global Impression of Severity (PGIS) questionnaire
timeFrame: At Week 26
measure: Change from baseline in patient-reported outcomes score as measured by the Short-form 36 health survey questionnaire version 2 (SF-36 v2)
timeFrame: At Week 26
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Uni Of Alabama At Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Los Angeles
country: United States
facility: Univ of California at Los Angeles
state: California
city: Orange
country: United States
facility: Univ Cali Irvine ALS Neuromuscular
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center .
state: California
city: Washington
country: United States
facility: Georgetown University Lombardi Cancer Center
state: District of Columbia
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: WA Uni School Of Med
state: Missouri
city: New Brunswick
country: United States
facility: Rut Univ for Translational Med Scie
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center .
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Comprehensive Transplant Ctr at OSU
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White Research
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
state: Tyrol
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Fortaleza
country: Brazil
facility: Novartis Investigative Site
state: CE
city: Brasilia
country: Brazil
facility: Novartis Investigative Site
state: DF
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Pernambuco
country: Brazil
facility: Novartis Investigative Site
state: Recife
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Botucatu
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Yantai
country: China
facility: Novartis Investigative Site
state: Shandong
city: Beijing
country: China
facility: Novartis Investigative Site
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: Shanxi
country: China
facility: Novartis Investigative Site
city: Ostrava
country: Czechia
facility: Novartis Investigative Site
state: Poruba
city: Prague 4
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Andhra Pradesh
city: Thiruvananthapuram
country: India
facility: Novartis Investigative Site
state: Kerala
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Chandigarh
country: India
facility: Novartis Investigative Site
state: Punjab
city: Chennai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Vellore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: Iruma-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Izumo-city
country: Japan
facility: Novartis Investigative Site
state: Shimane
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Martin
country: Slovakia
facility: Novartis Investigative Site
city: Ljubljana
country: Slovenia
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
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: