Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy

Atypical Hemolytic Uremic Syndrome Clinical Trial

— APPELHUS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04889430
• Other study ID #: CLNP023F12301
• Secondary ID: 2020-005186-13
• Status: Recruiting
• Phase: Phase 3
• Start date: January 17, 2022
• Est. completion date: January 6, 2026

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 determine whether iptacopan (LNP023) is efficacious and safe for the treatment of aHUS in adult patients who are treatment naive to complement inhibitor therapy.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 6, 2026
• Est. primary completion date: December 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 e (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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Iptacopan
Iptacopan 200mg twice daily oral

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Innsbruck	Tyrol
Austria	Novartis Investigative Site	Wien
Brazil	Novartis Investigative Site	Belo Horizonte	MG
Brazil	Novartis Investigative Site	Botucatu	SP
Brazil	Novartis Investigative Site	Brasilia	DF
Brazil	Novartis Investigative Site	Fortaleza	CE
Brazil	Novartis Investigative Site	Pernambuco	Recife
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Salvador
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanxi
China	Novartis Investigative Site	Yantai	Shandong
Czechia	Novartis Investigative Site	Ostrava	Poruba
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 4
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion Crete
Greece	Novartis Investigative Site	Thessaloniki	GR
India	Novartis Investigative Site	Chandigarh	Punjab
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Thiruvananthapuram	Kerala
India	Novartis Investigative Site	Vellore	Tamil Nadu
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Iruma-gun	Saitama
Japan	Novartis Investigative Site	Izumo-city	Shimane
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Martin
Slovenia	Novartis Investigative Site	Ljubljana
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taoyuan
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United States	University of New Mexico Clin and Transl Science Ctr	Albuquerque	New Mexico
United States	Montefiore Medical Center .	Bronx	New York
United States	Cleveland Clinic Foundation Nephrology and Hypertension	Cleveland	Ohio
United States	Duke University Medical Center .	Durham	North Carolina
United States	USC Norris Cancer Center	Los Angeles	California
United States	Baylor Scott and White Research .	Temple	Texas
United States	Harbor-UCLA Medical Center .	Torrance	California
United States	Georgetown University Lombardi Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  China,  Czechia,  Greece,  India,  Japan,  Korea, Republic of,  Slovakia,  Slovenia,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody	The number/percentage of participants treated with iptacopan achieving complete thrombotic microangiopathy (TMA) response during 26 weeks of study treatment.; Complete TMA Response is defined as (1) hematological normalization in platelet count (platelet count =150 x 10^9/L) and LDH (below ULN), and (2) improvement in kidney function (= 25% serum creatinine reduction from baseline), maintained for two measurements obtained at least four weeks apart, and any measurement in between	26 weeks of study treatment
Primary	Long term safety and efficacy evaluations	Long term (one year) safety, tolerability and efficacy of iptacopan via 1) safety evaluations including adverse events/serious adverse events, safety laboratory parameters, vital signs etc. after 52 weeks of study treatment, and 2) efficacy evaluations including complete TMA response, hematological parameters (platelets, LDH, hemoglobin), eGFR, PROs after 52 weeks of study treatment	52 weeks of study treatment
Secondary	Time to achieve complete TMA response	Effect of study treatment iptacopan on time to complete TMA response during the first 26 weeks of study treatment	26 weeks of study treatment
Secondary	Percentage of participants with increase from baseline in hemoglobin levels = 2 g/dL	Response is defined as the percentage of participants with an increase in hemoglobin of = 2 g/dL from baseline, observed at two measurements obtained at least 4 weeks apart and any measurement in between during 26 weeks of study treatment	26 weeks of study treatment
Secondary	Change from baseline on hematologic parameters	Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at Week 26	At week 26
Secondary	Percentage of participants on dialysis	For participants requiring dialysis within 5 days prior to iptacopan treatment initiation, the number of participants who no longer require dialysis through 26 weeks of study treatment will be evaluated by means of proportion and corresponding confidence interval	26 weeks of study treatment
Secondary	Change from baseline on estimated glomerular filtration rate	Change from baseline in eGFR after 26 weeks of study treatment.	At week 26
Secondary	Change from baseline in chronic kidney disease (CKD) stage	Change from baseline in CKD stage (1-5) based on eGFR categories at Week 26	At week 26
Secondary	Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire	Change from baseline in patient-reported outcomes scores for FACIT-Fatigue Questionnaire at Week 26	At week 26
Secondary	Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire	Change from baseline in patient-reported outcomes scores for the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire at Week 26	At Week 26
Secondary	Change from baseline in patient-reported outcomes score as measured by the Patient Global Impression of Severity (PGIS) questionnaire	Change from baseline in patient-reported outcomes scores for Patient Global Impression of Severity (PGIS) at Week 26	At Week 26
Secondary	Change from baseline in patient-reported outcomes score as measured by the Short-form 36 health survey questionnaire version 2 (SF-36 v2)	Change from baseline in patient-reported outcomes scores for Short-form 36 health survey questionnaire version 2 (SF-36 v2) at Week 26	At Week 26