| CTRI Number |
CTRI/2024/05/066893 [Registered on: 07/05/2024] Trial Registered Prospectively |
| Last Modified On: |
10/04/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Study to check the efficiency and safety of iptacopan in participants with glomerular injury |
|
Scientific Title of Study
|
A multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in idiopathic immune complex mediated membranoproliferative glomerulonephritis (IC-MPGN). |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2022-002328-11 |
EudraCT |
| CLNP023B12302-00 (Original Protocol) dated 02 Dec 2022 |
Protocol Number |
| NCT05755386 |
ClinicalTrials.gov |
|
|
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
Mumbai
MAHARASHTRA
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
Mumbai
MAHARASHTRA
India
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
Mumbai
MAHARASHTRA
India
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
|
|
|
Countries of Recruitment
|
Argentina
Brazil
Canada
Czech Republic
France
Germany
Israel
Italy
Japan
Poland
South Africa
Spain
Turkey
United Kingdom
United States of America
Viet Nam
India |
Sites of Study
Modification(s)
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DrAmit Pasari |
"Saraswati Kidney Care Center ( A Unit of SS Multispecialty) |
Research Department-C Block, Flat no.010, Beside Saraswati Kidney Care Center (A unit of SS Multispeciality), 13, New Sneh Nagar,
Near Jaiprakash Metro Station, Jaitala Road, Nagpur- 440015"
Mumbai
MAHARASHTRA |
9422164630
dramit28@yahoo.co.in |
| DrSoumita Bagchi |
All India Institute of Medical Science |
Room No 3101 A, 3rd Floor Teaching Block,Department of Nephrology, Ansari Nagar, Delhi-29
East
DELHI |
9871911744
soumita_bagchi@yahoo.co.in |
| DrVipul Chakurkar |
KEM Hospital, Pune |
KEM Hospital, Renal Unit 2nd floor, Diamond jubilee Building, Sardar Moodliar Road, Rasta Peth, Pune, 411011
Pune
MAHARASHTRA |
9403207328
chakurkarvipul@gmail.com |
| Dr Sunil R |
Kempegowda Institute of Medical Sciences Hospital and Research Centre |
Kempegowda Institute of Medical Sciences Hospital and Research Centre, KR Road, VV Puram, Bengaluru, Karnataka 560004
Bangalore
KARNATAKA |
08026624870
SRNEPHRO@GMAIL.COM |
| Dr Sree Bhushan Raju |
Nizams Institute of Medical Sciences |
Nizam’s Institute of Medical Sciences, 2nd floor, Room 229, Millenium block, Punjagutta, Hyderabad, Telangana - 500082
Hyderabad
TELANGANA |
9030292929
sreebhushan@hotmail.com |
| Dr Dharmedra Singh Bhadauria |
Sanjay Gandhi Psotgraduate Institute of Medical Sciences |
Deparrtment of Nephrology,Lucknow- 226014
Lucknow
UTTAR PRADESH |
0522-2495187
drdharm1@rediffmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| IEC-Sanjay Gandhi Psotgraduate Institute of Medical Sciences |
Submittted/Under Review |
| Institute Ethics Committee All India Institute of Medical Sciences |
Approved |
| KEM Hospital Research Centre Ethics Committee, Pune |
Approved |
| KIMS Institutional Ethics Committee Kempegowda Institute Of Medical Sciences |
Approved |
| Nizams Institute Ethics Committee |
Approved |
| SKCC Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: N08||Glomerular disorders in diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
iptacopan (LNP023) |
200 mg taken orally twice a day for 06 months |
| Comparator Agent |
NA |
NA |
| Intervention |
Placebo |
Matching Placebo taken orally twice a day for 06 months |
|
|
Inclusion Criteria
|
| Age From |
12.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
Diagnosis of idiopathic IC-MPGN as confirmed by kidney biopsy within 12 months prior to enrollment in adults and within 3 years of enrollment in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available in an adult participant, this must be obtained at screening (performed and assessed locally for adults only).
Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of an ACEI or ARB for at least 90 days (or as according to local guidelines). The doses of other drugs administered to reduce proteinuria and control the disease including mycophenolic acids (MPAs - mycophenolate mofetil or mycophenolate sodium), corticosteroids, SGLT2 inhibitors and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization
UPCR ≥ 1.0 g/g (≥ 113 mg/mmol) sampled from the first morning void urine sample at Day -75 and Day -15
Estimated GFR (using the chronic kidney disease [CKD]-EPI formula for adult participants and modified Schwartz formula for adolescents aged 12 to 17 years) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -15.
Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care.
• If not previously vaccinated, or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care. |
|
| ExclusionCriteria |
| Details |
Participants who have undergone cell or solid organ transplantation, including kidney transplantation.
Participants diagnosed with secondary IC-MPGN including but not limited to any of the following conditions:
Deposition of antigen-antibody immune complexes as a result of any chronic infections, including
Hepatitis C virus (HCV) including HCV-associated mixed cryoglobulinemia, hepatitis B virus (HBV);
Bacterial-endocarditis, infected ventriculo-atrial shunt, visceral abscesses, leprosy, meningococcal meningitis; chronic bacterial infections
Protozoa/other infections- malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histroplasmosis
Renal deposition of immune complexes as a result of a systemic autoimmune disease:
Systemic lupus erythematosus (SLE)
Sjögren syndrome
Rheumatoid arthritis
Mixed connective tissue disease
Deposition of monoclonal immunglobulins because of a monoclonal gammopathy due to plasma cell or B cell disorders. Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care.
Fibrillary glomerulonephritis
Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with kidney biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli on the most recent biopsy.
Kidney biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%.
Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration or the presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration.
A history of recurrent invasive infections caused by encapsulated organisms, e.g., Neisseria meningitidis and Streptococcus pneumoniae.
The use of inhibitors of complement factors (e.g., Factor B, Factor D, complement 3 (C3) inhibitors, anti-Complement 5 (C5) antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit.
The use of immunosuppressants (except MPAs), cyclophosphamide or systemic corticosteroids at a dose >7.5 mg/day (or equivalent for a similar corticosteroid medication) within 90 days of study drug administration.
The use of MPAs is not permitted within 90 days prior to randomization in India, as per the local health authority requirement.
Acute post-infectious glomerulonephritis at screening, based upon the opinion of the investigator.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Double Blind Double Dummy |
|
Primary Outcome
|
| Outcome |
TimePoints |
| What is the treatment effect of iptacopan versus placebo on reduction of protein in urine in participants with IC-MPGN |
Lower levels of protein in urine measured by UPCR (Urine Protein Creatine Ratio) after 6 months of iptacopan treatment. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To demonstrate the superiority of iptacopan vs. placebo in improving estimated Glomerular Filtration Rate (eGFR |
Change in Estimated Glomerular Filtration Rate (eGFR) measurement after 6 months of iptacopan treatment |
| To demonstrate the superiority of iptacopan vs. placebo in the proportion of participant who achieved a composite renal endpoint |
Change from day 1 to 6 months in the reported fatigue levels (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue] score) |
| To demonstrate the superiority of iptacopan compared to placebo in improvement of patient-reported fatigue. |
Number of adverse events & any discontinuations from study due to these adverse events during the first 6 months of treatment. |
| To evaluate the safety & tolerability of iptacopan compared to placebo during the 6-month double-blind period. |
In adolescents, the number of adverse events relating to heart function (e.g., Blood pressure & heart rate) throughout the treatment period. |
|
|
Target Sample Size
|
Total Sample Size="68"
Sample Size from India="6"
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 3 |
|
Date of First Enrollment (India)
|
17/05/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
31/07/2023 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
The purpose of this Phase III study is to evaluate the efficacy and safety of iptacopan compared to placebo (and standard of care) in participants (adults and adolescents aged 12-17 years) with idiopathic (primary) IC-MPGN in native kidneys. The study duration will be up to 480 days, including the pre-treatment (screening) and post-treatment safety follow-up periods. The treatment duration will be up to 360 days. There will be up to four visits during the 90-day screening period/Run-in period, five visits in the first 6-month treatment period and three visits in the second 6-month treatment period After the end of study, participants will have the option to transition to an extension study and continue iptacopan treatment. |