FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2019/10/021809 [Registered on: 28/10/2019] Trial Registered Prospectively
Last Modified On: 02/07/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Efficacy and safety of LNP023 compared with rituximab in subjects with idiopathic membranous nephropathy 
Scientific Title of Study   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 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
2019-001734-34  EudraCT 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Private Limited 
Address  Novartis Healthcare Private Limited 6 and 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai India

Mumbai
MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Details of Contact Person
Scientific Query  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Private Limited 
Address  Novartis Healthcare Private Limited 6 and 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai India

Mumbai
MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Details of Contact Person
Public Query  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Private Limited 
Address  Novartis Healthcare Private Limited 6 and 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai India

Mumbai
MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Source of Monetary or Material Support  
Novartis Pharma AG, Novartis Campus 4056 – Basel, Switzerland 
 
Primary Sponsor  
Name  Novartis Healthcare Pvt Ltd 
Address  6 & 7 floor, Inspire BKC, G Block, BKC Main Road, Bandra Kurla Complex, Bandra (East), Mumbai – 400051,India 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Argentina
Czech Republic
France
Germany
India
Jordan
Netherlands
Russian Federation
Singapore
Spain
United Kingdom  
Sites of Study  
No of Sites = 5  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Soumita Bagchi  All India Institute of Medical Sciences  All India Institute of Medical Sciences, Dept. of Nephrology, 3rd Floor, RK OPD-Rajkumari , New Delhi-110029
New Delhi
DELHI 		 9871911744

soumita_bagchi@yahoo.co.in 
Dr Dinesh Khullar  Max Super Speciality Hospital  Max Super Speciality Hospital , 1 Press Enclave Road, Saket, New Delhi-110017
New Delhi
DELHI 		 9810124066

drdineshkhullar@gmail.com 
Dr Vivek Ruhela  Shri Mahant Indiresh Hospital  Shri Mahant Indiresh Hospital Patel Nagar Dehradun 248001 Uttarakhand, India
Dehradun
UTTARANCHAL 		 9721104868

vivekruhela@yahoo.com 
Dr Ashwani Gupta  Sir Ganga Ram Hospital  Sir Ganga Ram Hospital,SGRH Marg, Rajinder Nagar, New Delhi-110060, India
New Delhi
DELHI 		 9811049761

ashwani_gupta2002@yahoo.com 
Dr Rajasekara Chakravarthi Madarasu  Star Hospitals  Star Hospitals, 8-2-596/5, Road No-10, Banjara Hills, Hyderabad-500034
Hyderabad
TELANGANA 		 9391059322

rajasekarac@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 5  
Name of Committee  Approval Status 
Ethics Committee All India Institute of Medical Sciences  Approved 
Ethics Committee Sir Ganga Ram Hospital  Approved 
Institutional Ethics Committee SGRR Medical College  Approved 
Max Super Speciality Hospital   Approved 
Star Institutional Ethics committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: N042||Nephrotic syndrome with diffuse membranous glomerulonephritis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  LNP023  Regimen A: LNP023 10 mg b.i.d. p.o. for 4 weeks followed by LNP023 50 mg b.i.d. for 20 weeks Regimen B: LNP023 25 mg b.i.d. p.o. for 4 weeks followed by LNP023 200 mg b.i.d. for 20 weeks 
Comparator Agent  RITUXIMAB  Rituximab 1 g i.v. at Day 1 and Day 15 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1. Written informed consent must be obtained before any study assessment is performed.


2. Able to communicate well with the investigator, to understand and comply with the
requirements of the study.


3. Female or male adult (more than or equal to 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.


4. Anti-PLA2R antibody titer of more than or equal to 100 RU/mL at screening visit (based on the EuroImmun ELISA test).


5. Less than or equal to 50% reduction in both anti-PLA2R level and 24h urine protein between first measurement at screening or run-in visit and baseline.


6. Urine protein more than or equal to 3.5 g per 24h at run-in and baseline visits.


7. Estimated GFR (using the CKD-EPI formula)more than or equal to 45 mL per min per 1.73 m2 at screening visit.


8. Weight of at least 35 kg and body mass index (BMI) of at least 15 kg per m2.


9. 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.


10. 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.


11. Subject agrees to collect 24h urine sample at home and to bring it to the investigational
site at specific visits. 
 
ExclusionCriteria 
Details  1. 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)


2. Diagnostic renal biopsy showing evidence of crescent formation in glomeruli, suggestive
of an alternative or additional diagnosis to primary idiopathic MN.


3. Previous treatment with B-cell depleting or B-cell modifying agents such as, but not
limited to rituximab, belimumab, daratumomab or bortezomib.


4. 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 less than or equal to 10 mg prednisolone for at least 90 days prior to Day 1


5. Administration of any live vaccination within 4 weeks prior to Day 1


6. Previous treatment with gemfibrozil or strong CYP2C8 inhibitors such as clopidogrel within 7 days prior to Day 1


7. 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


8. 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


9. History of clinically significant ECG abnormalities, or any of the following ECG
abnormalities at screening or baseline visit:
a. QTcF more than 450 msec (males)
b. QTcF more than 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


10. 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


11. 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


12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic contraception during dosing and for 1 week after stopping of LNP023 or for 12 months after stopping rituximab. Basic
contraception methods include:
a. Barrier methods of contraception: Condom or Occlusive cap. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
All arms: To assess the efficacy of the LNP023 regimen B compared with rituximab  Ratio between baseline UPCR and UPCR at 24 weeks of treatment (from 24h urine collection) 
 
Secondary Outcome  
Outcome  TimePoints 
LNP023 arms: To assess the safety and tolerability of regimen A and regimen B of LNP023  ECG parameters, vital signs, safety laboratory data, physical exam and collection of AEs assessed from baseline until the end of the study visit. 
LNP023 arms: To assess the relationship between LNP023 systemic drug exposure and pharmacodynamics, mode-of-action markers and clinical efficacy  a. Plasma levels of Bb and sC5b-9
b. UPCR measured in first morning void
c. Non-compartmental parameters related to drug exposure 
LNP023 arms: To assess the difference in response between the low (regimen A) and high (regimen B) dose of LNP023  Ratio between baseline UPCR and UPCR at 24 weeks of treatment (from 24h urine collection) 
All arms: To assess the effect of LNP023 compared with rituximab on proteinuria remission and renal function  a. Proportion of subjects with a complete remission, defined as proteinuria less than or equal to 0.3 g per day at 24 weeks of treatment, derived from 24h urine collection
b. Proportion of subjects with a partial remission,
defined as reduction of proteinuria from baseline more than or equal to 50 percent plus final UP less than or equal to 3.5 g per 24h but more than 0.3 g per 24h at 24 weeks of treatment, derived from 24h urine collection 
LNP023 arms: To assess the
pharmacokinetics of LNP023 		 a. Plasma: non-compartmental parameters in plasma related to total parent drug, including, but not limited, to Tmax, Cmax, AUClast and
AUCtau will be calculated for each dose level.
b. Urine: renal plasma clearance derived from 24h urine at week 16. 
 
Target Sample Size   Total Sample Size="72"
Sample Size from India="20" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   31/10/2019 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  31/10/2019 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="8"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  
The purpose of this study is to ascertain the efficacy, safety, tolerability and pharmacokinetics of LNP023 over a 24-week treatment period compared with rituximab in subjects with idiopathic membranous nephropathy (MN). The primary end point of the study will be the ratio between baseline Urine Protein Creatinine Ratio (UPCR) and UPCR at 24 weeks of treatment (from 24h urine collection). The study will target subjects with idiopathic MN at high risk of disease progression, on the basis of anti-PLA2R antibody titre and high grade proteinuria.
 
Close