To find out whether LFG316 is able to reduce the destruction of red blood cells in patients with PNH

• Register: EUCTR
• Last refreshed on: 30 May 2022
• Main ID: EUCTR2014-005338-74-CZ
• Date of registration: 23/04/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: To find out whether LFG316 is able to reduce the destruction of red blood cells in patients with PNH
• Scientific title: An open-label proof of concept study to assess the efficacy, safety and pharmacokinetics of LFG316, an anti-C5 monoclonal antibody in patients with paroxysmal nocturnal hemoglobinuria (PNH) - CLFG316X2201
• Date of first enrolment: 17/06/2015
• Target sample size: 9
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005338-74
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Czechia, Japan, Lithuania

Contacts

• Name: Informacní služba – klin. hodnocení
• Affiliation: Novartis s.r.o.

• Name: Informacní služba – klin. hodnocení
• Affiliation: Novartis s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
•Male and female patients >= 18 years old with a diagnosis of PNH prior to screening. Based on local requirements (applicable in Czech Republic) only patients between the age of 18-65 (inclusive) with a diagnosis of PNH prior to screening may be eligible for inclusion in this study.
•A documented PNH clone size of =10% by RBCs and/or granulocytes, measured by GPI-deficiency on flow cytometry.
•Serum LDH levels at least 1.5-fold above the upper limit of normal (ULN) at screening.
•Negative pregnancy test for women of child bearing potential at screening.
•Previous vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 2 weeks prior to first dosing. Vaccination against meningitidis type B should be conducted if available and acceptable by local regulations, at least 2 weeks prior to first dosing.
•Subjects to be included in this study after protocol amendment 6 also have to fulfill criterion: PNH patients that are carriers of the C5 gene minor variants as defined by nucleic acid changes that lead to amino acid exchanges in position p.Arg885.
.Additional inclusion criteria for period 4
- Patients participating in period 3 of the current study who are willing to join long term extension study with LNP023 (CLNP023C12001B)
- Previous vaccination for the prevention of S. pneumoniae and H. influenzae at least 2 weeks prior to first dosing with LNP023 if locally available. If LNP023 treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment must be initiated.
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 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
•Known or suspected hereditary complement deficiency.
•History of recurrent meningitis, history of meningococcal meningitis despite vaccination
•Presence or suspicion (based on judgment of the investigator) of severe active bacterial infection within 2 weeks prior to first dose of LFG316, or severe recurrent bacterial infections .
•Under active therapy with other agents interfering with the complement system
•Co-morbidities that are a likely caused by underlying autoimmune diseases other than PNH
•Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 50 days after the last dose of LFG316.
•Severe concurrent co-morbidites,eg: patients with severe kidney disease (dialysis),advanced cardiac disease (NYHA class IV) severe pulmonary artierial hypertension (WHO classIV) severe or unstable thrombotic event not amenable to active treatment as judged by the investigator.
•Either on of the following laboratory abnormalities at screening:
a. Neutrophils <0.5 x 1000000000/L
b.Platelets<30x1000000000/L
.Prohibited medication : targeting complement pathway. For period 4 only :co-medications that inhibit multiple disposition mechanisms of LNP023, Strong CYP2C8 inhibitors such as Clopidogrel, Compounds that have a narrow therapeutic index and are substrates for Pglycoproteins


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

Health Condition(s) or Problem(s) studied

Paroxysmal nocturnal hemoglobinuria
MedDRA version: 21.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857

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

Intervention(s)

Product Code: LFG316
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: No
Current Sponsor code: LFG316
Other descriptive name: human monoclonal antibody directed against complement 5 protein
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Code: LFG316
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: No
Current Sponsor code: LFG316
Other descriptive name: human monoclonal antibody directed against complement 5 protein
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: iptacopan
Product Code: LNP023
Pharmaceutical Form: Capsule, hard
Other descriptive name:  LNP023 HYDROCHLORIDE SALT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: iptacopan
Product Code: LNP023
Pharmaceutical Form: Capsule, hard
Other descriptive name:  LNP023 HYDROCHLORIDE SALT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): •Reduction in serum LDH levels within the first 4 weeks of treatment
•Reduction in serum LDH levels over the entire treatment period.

Main Objective: •To assess the effect of LFG316 on the reduction of intravascular hemolysis in PNH patients

Secondary Objective: •To assess the tolerability and pharmacokinetics of LFG316 in patients with PNH

Timepoint(s) of evaluation of this end point: Weekly in Period 1 and every 14 days in Period 2.
Patients participating in extension Period 3 will roll over from the last dosing visit of period 2 to the first visit (which includes drug administration) of period 3. The same assessment schedule applied in Period 1 and 2 will be applied between the last dosing visit of Period 2 and the first visit of Period 3.
Patients participating in period 3 will have the option to complete the period 3 Follow up and Study Completion evaluation or to continue with study period 4 which is a pre-requisite for their eligibility to join the long-term extension study CLNP023C12001B.
Patients participating in period 4, will complete their Study Completion evaluation approximately one week after last LNP023 treatment administered as a part of this study.

Secondary Outcome(s)

Secondary end point(s): •Standard safety monitoring with increased vigilance for infections
•Measurement of serum concentrations of LFG316

Timepoint(s) of evaluation of this end point: Safety
Weekly in Period 1 and every 2 weeks in Period 2
Serum concentration
Weekly in Period 1
Every 4 weeks in Period 2
Patients participating in extension Period 3 will roll over from the last dosing visit of period 2 to the first visit (which includes drug administration) of period 3. The same assessment schedule applied in Period 1 and 2 will be applied between the last dosing visit of Period 2 and the first visit of Period 3.
Patients participating in period 3 will have the option to complete the period 3 Follow up and Study Completion evaluation or to continue with study period 4.
Patients participating in period 4, will complete their Study Completion evaluation approximately one week after last LNP023 treatment administered as a part of this study.

Secondary ID(s)

CLFG316X2201

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 13/05/2015
Contact: