Atypical Hemolytic Uremic Syndrome
Conditions
Keywords
LNP023, iptacopan, aHUS, atypical hemolytic uremic syndrome, thrombotic microangiopathy
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.
Interventions
DRUGIptacopan
Iptacopan 200mg twice daily oral
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label single arm study
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody | 26 weeks of study treatment | 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 |
| Long term safety and efficacy evaluations | 52 weeks of study treatment | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to achieve complete TMA response | 26 weeks of study treatment | Effect of study treatment iptacopan on time to complete TMA response during the first 26 weeks of study treatment |
| Percentage of participants with increase from baseline in hemoglobin levels ≥ 2 g/dL | 26 weeks of study treatment | 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 |
| Change from baseline on hematologic parameters | At week 26 | Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at Week 26 |
| Percentage of participants on dialysis | 26 weeks of study treatment | 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 |
| Change from baseline on estimated glomerular filtration rate | At week 26 | Change from baseline in eGFR after 26 weeks of study treatment. |
| Change from baseline in chronic kidney disease (CKD) stage | At week 26 | Change from baseline in CKD stage (1-5) based on eGFR categories at Week 26 |
| Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire | At week 26 | Change from baseline in patient-reported outcomes scores for FACIT-Fatigue Questionnaire at Week 26 |
| Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire | At Week 26 | Change from baseline in patient-reported outcomes scores for the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire at Week 26 |
| Change from baseline in patient-reported outcomes score as measured by the Patient Global Impression of Severity (PGIS) questionnaire | At Week 26 | Change from baseline in patient-reported outcomes scores for Patient Global Impression of Severity (PGIS) at Week 26 |
| Change from baseline in patient-reported outcomes score as measured by the Short-form 36 health survey questionnaire version 2 (SF-36 v2) | At Week 26 | Change from baseline in patient-reported outcomes scores for Short-form 36 health survey questionnaire version 2 (SF-36 v2) at Week 26 |
Countries
Brazil, China, Czechia, India, Japan, South Korea, Taiwan, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed