A randomized, treatment open-label, dose-blinded parallel group, three arm, proof-of-concept clinical trial to investigate the efficacy and safety of LNP023 compared with rituximab in the treatment of subjects with idiopathic membranous nephropathy



Short title: LNP023 & membr. GN

Investigated disease: membranöse GN

Principal Investigator: PD Dr. Adrian Schreiber


Clinic, Institute: Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin CVK - Leitung

Patient (diseased)
Age: 18 - 99
Gender: All
Last change: 26.09.2020

Back to Overview



You are here:

Study Description

Title

A randomized, treatment open-label, dose-blinded parallel group, three arm, proof-of-concept clinical trial to investigate the efficacy and safety of LNP023 compared with rituximab in the treatment of subjects with idiopathic membranous nephropathy

Short title

LNP023 & membr. GN

EudraCT-No.

2019-001734-34

General Short Description

A randomized, treatment open-label, dose-blinded parallel
group, three arm, proof-of-concept clinical trial to
investigate the efficacy and safety of LNP023 compared
with rituximab in the treatment of subjects with idiopathic
membranous nephropathy

Scientific Short Description

A randomized, treatment open-label, dose-blinded parallel
group, three arm, proof-of-concept clinical trial to
investigate the efficacy and safety of LNP023 compared
with rituximab in the treatment of subjects with idiopathic
membranous nephropathy

Investigated Disease, Health Issue

ICD-Code
  • N03.2 - Chronisches nephritisches Syndrom; Diffuse membranöse Glomerulonephritis

Inclusion Criteria

Age

18 - 99

Gender

All

Additional Inclusion Criteria

Written informed consent must be obtained before any assessment is performed
Able to communicate well with the investigator, to understand and comply with the requirements of the study
Female or male adult (≥18 years) subjects at screening visit with a diagnosis of idiopathic (primary) MN confirmed by renal biopsy within 24 months prior to screening. A renal biopsy may be taken at any time during the run-in period to confirm the diagnosis of MN and facilitate subject eligibility, if the most recent biopsy was performed greater than 24 months prior to the screening visit.
Anti-PLA2R antibody titer of ≥ 100 RU/mL at screening visit (based on the EuroImmun ELISA test).
≤50% reduction in both anti-PLA2R level and 24h urine protein between first measurement at screening or run-in visit and baseline.
Urine protein ≥ 3.5 g/24h at run-in and baseline visits.
Estimated GFR (using the CKD-EPI formula) ≥ 45 mL/min per 1.73 m2 at screening visit.
Weight of at least 35 kg and body mass index (BMI) of at least 15 kg/m2.
Receiving stable dose at the maximum recommended dose according to local guidelines or maximum tolerated dose of ACEi and/or ARB and/or statins and/or diuretics. The dose of ACEi or ARB must be stable for at least 8 weeks prior to Day 1, defined as <25% dose change over this 8 week period.
Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae (in accordance with local guidelines) at least 28 days prior to Day 1 and no longer than 5 years prior to Day 1.
Subject agrees to collect 24h urine sample at home and to bring it to the investigational site at specific visits.

Exclusion Criteria

Secondary causes of MN, e.g. systemic autoimmune diseases, solid or haematological malignancies, infections or chronic intake of drugs (e.g. gold salts, NSAIDs, penicillamines
Diagnostic renal biopsy showing evidence of crescent formation in glomeruli, suggestive of an alternative or additional diagnosis to primary idiopathic MN.
Previous treatment with B-cell depleting or B-cell modifying agents such as, but not limited to rituximab, belimumab, daratumomab or bortezomib.
Previous treatment with immunosuppressive agents such as cyclophosphamide, chlorambucil, mycophenolate mofetil (or equivalent), cyclosporine, tacrolimus or azathioprine within 90 days prior to Day 1. Low dose systemic corticosteroid therapy is permitted, though the subject should have been on stable dose equivalent to ≤10 mg prednisolone for at least 90 days prior to Day 1
Administration of any live vaccination within 4 weeks prior to Day 1
Previous treatment with gemfibrozil or strong CYP2C8 inhibitors such as clopidogrel within 7 days prior to Day 1
Use of other investigational drugs within 30 days (e.g. small molecules) or 5 half-lives of screening or until the expected pharmacodynamic effect has returned to baseline (e.g. biologics), whichever is longer; or longer if required by local regulations
History of malignancy of any organ system (other than localised basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years prior to screening start, regardless of whether there is evidence of local recurrence or metastases
History of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline visit:
QTcF >450 msec (males)
QTcF >460 msec (females)
History of familial long QT syndrome or known family history of Torsades de Pointes
Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
Presence or suspicion (based on judgment of the investigator) of active infection within 30 days prior to Day 1, or history of severe recurrent bacterial infections
Pregnancy or nursing (lactation), where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chrorionic Gonadotropin (hCG) laboratory test
Women of child bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing and for 1 week after stopping of LNP023 or ofr 12 months after stopping rituximab. Basic contraception methods include:
Barrier methods of contraception: Condom or Occlusive cap.
Use of oral, injected or implanted hormonal methods of contraception, or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception, or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception, you should have been stable on the same pill for a minimum of 3 months before taking the study treatment.
Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence and withdrawal are not acceptable methods of contraception.
Female sterilization (surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
Your sole partner is a vasectomized male who was sterilized at least 6 months prior to screening.
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.
If local regulations deviate from the contraception methods listed above and require more extensive measures to prevent

Characteristics

Studytype

Interventional

Studyphase

2

Back to Overview