A Study evaluating the safety and efficacy of LNP023 in patients with a blood disorder called paroxysmal nocturnal hemoglobinuria (PNH)

Phase 1

Active, not recruiting

Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
MedDRA version: 20.0Level: HLGTClassification code 10018911Term: Haemolyses and related conditionsSystem Organ Class: 10005329 - Blood and lymphatic system disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2017-000888-33-DE

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Recruiting

Sex: All

Target Recruitment: 15

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 <10.5 g/dL at baseline.
•PNH patients on stable regimen of standard of care complement blockade (monoclonal antibody with anti C5 activity) for at least 3 months prior to first treatment with LNP023.
•Previous vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 4 weeks prior to first dosing with LNP023. Vaccination against N. meningitidis type B should be conducted if available and acceptable by local regulations, at least 4 weeks prior to first dosing with LNP023 If LNP023 treatment has to start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment must be initiated.
•Previous vaccination for the prevention of S. pneumoniae and H. influenzae at least 4 weeks prior to first dosing with LNP023 If LNP023 treatment has to start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment must be initiated.
•Able to communicate well with the investigator, to understand and comply with the requirements of the study.
•For Part 2 of the study patients who as per judgment of Investigator
benefit from LNP023 treatment based on reduced hemolytic parameters
as compared to Screening and Baseline.

Other protocol defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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).<br>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)<br>To assess the plasma PK of LNP023 in PNH patients<br>;Primary end point(s): •LDH level at study week 13;Timepoint(s) of evaluation of this end point: Week 13

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •All safety parameters including: blood chemistry, hematology, urinalysis, ECG evaluation, vital signs, adverse events, transfusions, PROs<br>•Total and free hemoglobin, reticulocytes, LDH, C3 fragment deposition, PNH-type red blood cells, haptoglobin, bilirubin, red blood cell count, freedom from transfusion<br>•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

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