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

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2017-000888-33-FR
• Date of registration: 22/01/2018
• Prospective Registration: No
• Primary sponsor: Novartis Pharma AG
• Public title: A Study evaluating the safety and efficacy of LNP023 in patients with a blood disorder called paroxysmal nocturnal hemoglobinuria (PNH)
• Scientific title: An open label, single arm, multiple dose study to assess efficacy, safety, pharmacokinetics and pharmacodynamics of LNP023 when administered in addition to Standard of Care (SoC) in patients with paroxysmal nocturnal hemoglobinuria (PNH) with signs of active hemolysis
• Date of first enrolment: 15/01/2018
• Target sample size: 10
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000888-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy

Contacts

• Name: Information&Communication Médicales
• Affiliation: Novartis Pharma S.A.S

• Name: Information&Communication Médicales
• Affiliation: Novartis Pharma S.A.S

Key inclusion & exclusion criteria

Inclusion criteria:
•Written informed consent must be obtained before any assessment is performed.
•Male and female patients between the age of 18-75 (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).
•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).
•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.
•Previous vaccination for the prevention of S. pneumoniae and H. influenzae at least 4 weeks prior to first dosing with LNP023.
•Able to communicate well with the investigator, to understand and comply with the requirements of the study.

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, platelets <30x10E9/l neutrophils <1x10E9/l) as verified both at screening and at baseline (unless baseline was skipped)
•A positive HIV 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

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 milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 13

Primary end point(s): •LDH level at study week 13

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

Secondary Outcome(s)

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, C3 fragment deposition, haptoglobin, bilirubin, red blood cell count, freedom from transfusion
•Total drug LNP023 non-compartmental PK parameters, including but not limited to Cmax and AUC and trough evaluation

Timepoint(s) of evaluation of this end point: Entire study duration

Secondary ID(s)

CLNP023X2201

2017-000888-33-DE

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date:
Contact: