Paroxysmal Nocturnal Hemoglobinuria (PNH) MedDRA version: 20.0 Level: HLGT Classification code 10018911 Term: Haemolyses and related conditions System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Code: LNP023
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not yet established
Current Sponsor code: LNP023
Other descriptive name: LNP023 HYDROCHLORIDE SALT
Concentration unit: mg
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Written informed consent must be obtained before any assessment is performed. •Male and female patients between the age of 18-80 (inclusive) at baseline with a diagnosis of PNH based on documented clone size of =10% by RBCs and/or granulocytes, measured by GPI-deficiency on flow cytometry (screening or medical history data acceptable). •For Cohort 1 only: LDH values = 1.5x upper limit of the normal range for at least 3 pre-SoC dosing measurements taken in relation to 3 different SoC dosing dates over a maximum of 10 weeks prior to Day 1 (screening, baseline or medical history data acceptable). All the screening pre-SoC LDH values > 1x upper limit of normal range (for pre-SoC samples collected at the same day as SoC administration). For Cohort 2 only: LDH values = 1.25x upper limit of the normal range for at least 3 pre-SoC dosing measurements taken in relation to 3 different SoC dosing dates over a maximum of 10 weeks prior to Day 1 (screening, baseline or medical history data acceptable). All other screening pre-SoC LDH values have to be >1x upper limit of normal range (for pre-SoC samples collected at the same day as SoC administration). • For Cohort 2 only: Hemoglobin level =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: •Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment, or within 5 elimination half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations •Known or suspected hereditary complement deficiency at screening •History of hematopoietic stem cell transplantation as verified both at screening and at baseline (unless baseline was skipped) •Patients with laboratory evidence of bone marrow failure (reticulocytes <60x10E9/l or, platelets <30x10E9/l or neutrophils <1x10E9/l) as verified both at screening and at baseline (unless baseline was skipped) •A positive HIV, Hepatitis B (HBV) or Hepatitis C (HCV) test result at screening •Presence or suspicion (based on judgment of the investigator) of active infection within 2 weeks prior to first dose of LNP023, or history of severe recurrent bacterial infections •History of recurrent meningitis, history of meningococcal infections despite vaccination as verified both at screening and at baseline (unless baseline was skipped) •Patients on the immunosuppressive agents such as but not limited to cyclosporine, MMF, tacrolimus, cyclophosphamide, methotrexate less than 8 weeks prior to first treatment with LNP023 unless on a stable regimen for at least 6 3 months prior to first LNP023 dose. •Systemic corticosteroids administered at the dose of = 10 mg per day prednisone equivalent within less than 4 weeks prior to first treatment with LNP023 •Severe concurrent co-morbidities, e.g. patients with severe kidney disease (dialysis), advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), unstable thrombotic event not amenable to active treatment as judged by the investigator both at screening and at baseline (unless baseline was skipped) •Any medical condition deemed likely to interfere with the patient’s participation in the study, or likely to cause serious adverse events during the study •Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception from first dosing with LNP023 until EOS. Other protocol defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of LNP023 on the reduction of chronic hemolysis in PNH patients when administered in addition to SoC (monoclonal antibody with anti C5 activity).;Secondary Objective: To assess the safety and tolerability of LNP023 in patients with PNH when administered in addition to SoC (monoclonal antibody with anti C5 activity). To assess the effect of LNP023 on markers of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) To assess the plasma PK of LNP023 in PNH patients ;Primary end point(s): •LDH level at study week 13;Timepoint(s) of evaluation of this end point: Week 13 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •All safety parameters including: blood chemistry, hematology, urinalysis, ECG evaluation, vital signs, adverse events, transfusions, PROs •Total and free hemoglobin, reticulocytes, LDH, C3 fragment deposition, PNH-type red blood cells, haptoglobin, bilirubin, red blood cell count, freedom from transfusion •Non-compartmental PK parameters or LNP023 in plasma, including but not limited to Cmax, Tmax and AUC and Ctrough;Timepoint(s) of evaluation of this end point: Entire study duration | — |
Countries
France, Germany, Italy
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed