| CTRI Number |
CTRI/2021/10/037662 [Registered on: 28/10/2021] Trial Registered Prospectively |
| Last Modified On: |
20/04/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
Study of LNP023 (iptacopan)to access efficacy and safety in patients who are 18 or more years of age diagnosed with atypical hemolytic uremic syndrome who have never received treatment with complement inhibitors |
|
Scientific Title of Study
|
A multicenter, single-arm, open label trial to evaluate efficacy and safety of oral, twice daily LNP023 (Iptacopan) in adult atypical hemolytic uremic syndrome (aHUS) patients who are naive to complement inhibitor therapy. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2020-005186-13 |
EudraCT |
| CLNP023F12301 Version 00 dated 2 Mar 2021 |
Protocol Number |
| NCT04889430 |
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 |
| 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)
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)
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
|
Austria
Brazil
China
Czech Republic
Greece
Hungary
India
Japan
Republic of Korea
Russian Federation
Taiwan
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr B SUBBA RAO MD DNB Nephrology |
Apollo Hospitals |
Department of Nephrology
Apollo Hospitals,
No.21, Greams Lane, Off Greams Road,
Chennai- 600 006
Tamil Nadu, India
Chennai
TAMIL NADU |
8939526822
subbaraobudithi@gmail.com |
| DrSantosh Varughese |
Christian Medical College |
Department of Nephrology
Christian Medical College, Dr.Ida Scudder Road
Vellore- 632004, Tamil Nadu,
India
Vellore
TAMIL NADU |
9442380267
santosh@cmcvellore.ac.in |
| Dr Noble Gracious S S |
GOVERNMENT MEDICAL COLLEGE TRIVANDRUM |
GOVERNMENT MEDICAL COLLEGE TRIVANDRUM,
SUPER SPECIALITY BLOCK,
DEPT OF NEPHROLOGY,
TRIVANDRUM 695011,
KERALA.
Thiruvananthapuram
KERALA |
9446390313
noblegracious@hotmail.com |
| Dr Vipul Chakurkar |
KEM Hospital |
Saradra Moodliar Road Rasta Oeth Pune 411011
Pune
MAHARASHTRA |
9403207328
chakurkarvipul@gmail.com |
| Dr MANISHA SAHAY |
OSMANIA GENERAL HOSPITAL |
DEPT OF NEPHROLOGY
QQDC BUILDING 3RD FLOOR
OSMANIA GENERAL HOSPITAL,
AFZALGUNJ
HYDERABAD- 500012
TELENGANA
Hyderabad
TELANGANA |
914024607007
drmanishasahay@gmail.com |
| DrRaja Ramachandran |
Post Graguate institute of Medical Education and Research, (PGIMER) |
Department of Nephrology, Ground Floor, C-block, Nehru Hospital, Post Graguate institute of Medical Education and Research, (PGIMER), Chandigarh, Sector-12, 160012
Chandigarh
CHANDIGARH |
9216958874
drraja1980@gmail.com |
| Dr Dharmedra Singh Bhadauria |
Sanjay Gandhi Postgraduate Institute of Medical Sciences |
Department of Nephrology, Raebareli Road, Lucknow, Uttar Pradesh
Lucknow
UTTAR PRADESH |
9919737544
drdharm1@rediffmail.com |
| Dr Amit Pasari |
Saraswati Kidney Care Center |
3, Jaitala road, near Jaiprakash Nagar Metro Station, New Sneh Nagar, Nagpur, Maharashtra 440015
Nagpur
MAHARASHTRA |
9422164630
dramit28@yahoo.co.in |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| IEC- Dr AMit Pasari |
Approved |
| IEC- Dr Budditi Subba Rao |
Approved |
| IEC- DR Manisha Sahay |
Approved |
| IEC- Dr Noble Gracious |
Approved |
| IEC-Vipul CHakurkar |
Approved |
| Institute ETHICS COMMITTEE, Dr. Dharmedra Singh Bhadauria |
Approved |
| Institutional Ethics Committee, Dr.Raja Ramachandran |
Approved |
| Institutional Review Board (IRB) & The Ethics Committee Carmon Block, Dr.Santosh Varughese |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D593||Hemolytic-uremic syndrome, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
LNP023 (iptacopan) |
dose of 200 mg (Capsule) b.i.d; Treatment duration is 52 Weeks (Core treatment period is 26 weeks and Extension Treatment period is 26 Ewwks); Route of Administration is Oral. |
| Comparator Agent |
NA |
NA |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1-Male and female patients ≥ 18 years of age with evidence of thrombotic microangiopathy (TMA), including thrombocytopenia, evidence of hemolysis, and acute kidney injury, based on the following laboratory findings:
2-Platelet count <150x109/L during the Screening Period or within 28 days prior to the start of the Screening Period, and
3-LDH ≥1.5 x upper limit of normal (ULN) during the Screening Period or within 28 days prior to the start of the Screening Period and hemoglobin
≤ lower limit of normal (LLN) for age and gender during the Screening Period or within 28 days prior to the start of the Screening Period, and
• Serum creatinine ≥ULN during the Screening Period (patients requiring dialysis for acute kidney injury are eligible)
• Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations, at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination or before vaccination is given, prophylactic antibiotic treatment must be
administered at the start of study treatment and for at least 2 weeks after vaccination
4-If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given according to local regulations. The vaccines should be given at least 2 weeks prior to first study drug administration. If iptacopan study treatment has to start earlier than 2 weeks post vaccination or before vaccination is given, prophylactic antibiotic treatment must be administered at the start of study medication and for at least 2 weeks after vaccination.
5-Among patients with a kidney transplant, (a) known history of aHUS prior to current kidney transplantation, or (b) no known history of aHUS, and persistent evidence of TMA at least 4 days after modifying the immunosuppressive regimen |
|
| ExclusionCriteria |
| Details |
1-Treatment with complement inhibitors, including anti-C5 antibody
2-ADAMTS13 deficiency, and/or Shiga toxin-related hemolytic uremic syndrome (STX-HUS), and/or Positive direct Coombs test
3-Identified drug exposure-related HUS or HUS related to known genetic defects of cobalamin C metabolism or known diacylglycerol kinase ε (DGKE) mediated aHUS
4-Receiving PE/PI, for 28 days or longer, prior to the start of screening for the current TMA
5-Bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT), heart, lung, small bowel, pancreas, or liver transplantation
6-In patients with a kidney transplant, acute kidney dysfunction consistent with the diagnosis of transplantation failure due to acute/chronic active T-Cell mediated rejection (TCMR) and/or active/chronic active antibody-mediated rejection (ABMR) according to Banff 2017 criteria
7-Among patients with native kidney, history of any kidney disease other than aHUS, such as:
8-Known kidney biopsy finding suggestive of underlying disease other than aHUS
9-Kidney ultrasound finding demonstrating small kidneys suggestive of chronic kidney failure
10-Known family history and/or genetic diagnosis of non-complement mediated genetic kidney disease (eg, focal segmental glomerulosclerosis)
11-Liver disease or liver injury at screening
12-Patients with sepsis, severe systemic infection or COVID-19 infection
13-Presence of systemic infections (bacterial, viral, fungal or parasitic) that, in the opinion of the Investigator, confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease
14-Active infection, or history of recurrent invasive infections, caused by encapsulated bacteria (i.e. meningococcus, pneumococcus), or H. influenzae
15-Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome
16-Chronic hemo- or peritoneal dialysis |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| The primary objective (performed at the end of the Core Treatment period (i.e the first 26 weeks) is: To assess the proportion of participants treated with iptacopan achieving complete thrombotic microangiopathy (TMA) response during 26 weeks of study treatment. |
End of Week 26 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To assess the effect of iptacopan on-
-time to complete TMA response
-hematologic parameters (platelets, LDH, hemoglobin)
-dialysis requirement status
-estimated glomerular filtration rate (eGFR)
-chronic kidney disease (CKD) stage
-patient-reported overall fatigue severity and health-related quality of life
-To assess safety and tolerability of iptacopan
-• To assess the proportion of participants achieving an increase from baseline in hemoglobin levels of ≥ 2 g/dL |
At the end of Week 26 |
|
|
Target Sample Size
|
Total Sample Size="50"
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)
|
18/11/2021 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
01/09/2021 |
| 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)
|
Other (Terminated) |
| Recruitment Status of Trial (India) |
Other (Terminated) |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
The study is designed as a multicenter, single-arm, open label study to
demonstrate the efficacy and safety of LNP023 (iptacopan) at a dose of 200 mg
b.i.d. in adult patients with aHUS who are treatment naive to complement
inhibitor therapy (including anti-C5 antibody). The study will assess the
effects of iptacopan on a range of efficacy assessments relevant to aHUS
including hematological and kidney parameters, dialysis requirement, changes in
chronic kidney disease (CKD) stage, as well as patient reported outcomes (PRO)
for fatigue and quality of life. This study will serve as the pivotal trial for
the development of iptacopan as a treatment for patients with aHUS. |