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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04889430
Other study ID # CLNP023F12301
Secondary ID 2020-005186-13
Status Recruiting
Phase Phase 3
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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