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CTRI Number  CTRI/2021/10/037351 [Registered on: 18/10/2021] Trial Registered Prospectively
Last Modified On: 20/04/2026
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 of efficacy and safety of iptacopan in patients with C3 glomerulopathy 
Scientific Title of Study   A multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in complement 3 glomerulopathy 
Trial Acronym  APPEAR-C3G 
Secondary IDs if Any  
Secondary ID  Identifier 
2020-004589-21  EudraCT 
CLNP023B12301; Version 0.0; Date- 3 Mar 2021  Protocol Number 
NCT04817618  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 MAHARASHTRA 400051 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 MAHARASHTRA 400051 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 MAHARASHTRA 400051 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
Belgium
Brazil
Canada
China
Czech Republic
France
Germany
India
Israel
Italy
Japan
Netherlands
Spain
Switzerland
Turkey
United Kingdom
United States of America
Greece  
Sites of Study  
No of Sites = 4  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
DrSoumita Bagchi  All India Institute of Medical Science  Department of Nephrology, AIIMS, Ansari Nagar, Delhi-29
New Delhi
DELHI 		 9871911744

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

drdineshkhullar@gmail.com 
Dr Dharmandr Bhadauria  Sanjay Gandhi Psotgraduate Institute of Medical Sciences  Raebareli Road, Lucknow
Lucknow
UTTAR PRADESH 		 080042494367

ddharm@sgpgi.ac.in 
Dr Vivek Ruhela  Shri Mahant Indiresh Hospital  Research Room, Shri Mahant Indiresh Hospital, Patel Nagar, Dehradun-248001, India
Dehradun
UTTARANCHAL 		 9721104868

vivekruhela@yahoo.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 5  
Name of Committee  Approval Status 
Institutional ETHICS COMMITTEE, Dr. Dharmandr Bhadauria  Approved 
Institutional Ethics committee- Clinical studies, Dr Partha Saradhi  Approved 
InstitutionalEthics Committee, Dr. Soumita Bagchi  Approved 
InstitutionalEthics Committee, Dr. Vivek Ruhela  Approved 
Max Healthcare Ethics Committee, Dr. Dinesh Khulllar  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: N033||Chronic nephritic syndrome with diffuse mesangial proliferative glomerulonephritis, (2) ICD-10 Condition: N036||Chronic nephritic syndrome with dense deposit disease,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Iptacopan (LNP023)  200 mg Capsules b.i.d. Treatment period- 12 Months 
Comparator Agent  Placebo  Placebo capsules matching those for 200 mg capsules, b.i.d. Treatment period- 12 Months (of which placebo would be given for 6 months and then all participants would receive study drug for the remaining 6 months) 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Both 
Details  Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available, confirmation may be obtained using tissue from the Day -45 biopsy for local assessment.

Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for at least 90 days. The doses of other antiproteinuric medications including mycophenolic acids, corticosteroids and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization.

Reduced serum C3 (defined as less than 0.85 x lower limit of the central laboratory normal range) at Screening.

UPCR ≥ 1.0 g/g sampled from the first morning void urine sample at Day -75 and Day -15.

Estimated GFR (using the CKD-EPI formula) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -15.

Vaccination against Neisseria meningitidis infection prior to the start of study treatment. If the patient 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 study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.

If not previously vaccinated, or if a booster is required, vaccination against Streptococcus pneumoniae and 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 study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated. 
 
ExclusionCriteria 
Details  Participants who have received any cell or organ transplantation, including kidney transplantation.

Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months) with renal biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli.

Renal biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%.

Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care.

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., meningococcus or pneumococcus.

The use of inhibitors of complement factors (e.g., Factor B, Factor D, C3 inhibitors, anti Complement 5 (C5) antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit.

The use of immunosuppressants (except mycophenolic acids), cyclophosphamide or systemic corticosteroids at a dose >7.5 mg/day (or equivalent for a similar medication) within 90 days of study drug administration. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
The primary objective of the study is:
To demonstrate the superiority of iptacopan (200 mg b.i.d.) compared to placebo
in reducing proteinuria at 6 months of treatment.
The primary clinical question of interest is:
What is the effect of iptacopan vs. placebo on log-transformed ratio to baseline in
urinary protein/creatinine ratio (UPCR, sampled from a 24-hour urine collection)
at 6 months. 		 Log-transformed ratio to baseline in UPCR (sampled from
a 24-hour urine collection) at 6 months. 
 
Secondary Outcome  
Outcome  TimePoints 
To demonstrate the superiority
of iptacopan vs. placebo in
improving eGFR and in the
proportion of participants who
achieved a composite renal
endpoint.
To demonstrate the effect of
iptacopan vs placebo in
reducing glomerular
inflammation in the kidney.
To assess the effect of
iptacopan compared to placebo
in improvement of patientreported
fatigue.
To evaluate the safety and
tolerability of iptacopan
compared to placebo. 		 At 6 Months of treatment. 
 
Target Sample Size   Total Sample Size="68"
Sample Size from India="8" 
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)   19/11/2021 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  28/07/2021 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="4"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Closed to Recruitment of Participants 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details    
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 3 study is to evaluate the efficacy and safety of iptacopan compared to placebo (and standard of care) in patients with native C3G. The study aims to demostrate a reduction in proteinuria and improvement in estimated Glomerular Filtration Rate (eGFR) in participants treated with iptacopan compared to placebo. Kidney biopsies will be performed to assess histopathological reductions in glomerular inflammation and Complement 3 (C3) deposition, and improvement in fatigue will be evaluated. Complement alternative pathway (AP) dysregulation is believed to underlie the clinical
manifestations and progression of C3G. Serum C3 and other complement pathway biomakers will be assessed to demonstrate that ipatacopan reduces AP activity and targets the underlying cause of disease.
 
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