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.
Brief Title
Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome 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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-888-669-6682
Central Contact Email
novartis.email@novartis.com
Central Contact Role
Contact
Central Contact Phone
+41613241111
Completion Date
Completion Date Type
Estimated
Conditions
Atypical Hemolytic Uremic Syndrome
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
* 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
Inclusion Criteria
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
inclusion/
* 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
inclusion/
Gender
All
Gender Based
false
Keywords
LNP023
iptacopan
aHUS
atypical hemolytic uremic syndrome
thrombotic microangiopathy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
18 Years
NCT Id
NCT04889430
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CLNP023F12301
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
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
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
Outcome Measure
Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody
Outcome Time Frame
26 weeks of study treatment
Outcome Description
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
Outcome Measure
Long term safety and efficacy evaluations
Outcome Time Frame
52 weeks of study treatment
Secondary Ids
Secondary Id
2020-005186-13
Secondary Outcomes
Outcome Description
Effect of study treatment iptacopan on time to complete TMA response during the first 26 weeks of study treatment
Outcome Time Frame
26 weeks of study treatment
Outcome Measure
Time to achieve complete TMA response
Outcome Description
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
Outcome Time Frame
26 weeks of study treatment
Outcome Measure
Percentage of participants with increase from baseline in hemoglobin levels ≥ 2 g/dL
Outcome Description
Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at Week 26
Outcome Time Frame
At week 26
Outcome Measure
Change from baseline on hematologic parameters
Outcome Description
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
Outcome Time Frame
26 weeks of study treatment
Outcome Measure
Percentage of participants on dialysis
Outcome Description
Change from baseline in eGFR after 26 weeks of study treatment.
Outcome Time Frame
At week 26
Outcome Measure
Change from baseline on estimated glomerular filtration rate
Outcome Description
Change from baseline in CKD stage (1-5) based on eGFR categories at Week 26
Outcome Time Frame
At week 26
Outcome Measure
Change from baseline in chronic kidney disease (CKD) stage
Outcome Description
Change from baseline in patient-reported outcomes scores for FACIT-Fatigue Questionnaire at Week 26
Outcome Time Frame
At week 26
Outcome Measure
Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire
Outcome Description
Change from baseline in patient-reported outcomes scores for the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire at Week 26
Outcome Time Frame
At Week 26
Outcome Measure
Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire
Outcome Description
Change from baseline in patient-reported outcomes scores for Patient Global Impression of Severity (PGIS) at Week 26
Outcome Time Frame
At Week 26
Outcome Measure
Change from baseline in patient-reported outcomes score as measured by the Patient Global Impression of Severity (PGIS) questionnaire
Outcome Description
Change from baseline in patient-reported outcomes scores for Short-form 36 health survey questionnaire version 2 (SF-36 v2) at Week 26
Outcome Time Frame
At Week 26
Outcome Measure
Change from baseline in patient-reported outcomes score as measured by the Short-form 36 health survey questionnaire version 2 (SF-36 v2)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Irina Murakhovskaya
Investigator Email
imurakho@montefiore.org
Investigator Phone
IMURAKHO