IgA NephropathyPhase 2NCT03373461
Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammation
A Phase 2 study testing LNP023 in people with IgA Nephropathy, run by Novartis Pharmaceuticals at 56 sites in 25 countries.
Trial summary
Efficacy and safety of LNP023 in IgAN patients Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- IgA Nephropathy
- What is being tested?
- LNP023
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 56 sitesin 25 countries
- Study dates
- 7 Feb 2018to 22 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female and male patients above 18 years of age with a biopsy-verified IgA nephropathy and where the biopsy was performed within the prior three years.
- Patients must weigh at least 35 kg to participate in the study, and must have a body mass index (BMI) within the range of 15 - 38 kg/m2. BMI = Body weight (kg) / [Height (m)]2
- Measured Glomerular Filtration Rate (GFR) or estimated GFR (using the CKD-EPI formula) ≥30 mL/min per 1.73 m2
- Urine protein ≥1 g/24hr at screening and ≥0.75 g / 24h after the run- in period
- Vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 30 days prior to first dosing with LNP023. Vaccination against N. meningitidis type B, S. pneumoniae and H. influenzae should be conducted if available and acceptable by local regulations, at least 30 days prior to first dosing with LNP023
- All patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB therapy for the individual, antihypertensive therapy or diuretics for at least 90 days before dosing
Who cannot join
- Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy
- Patients previously treated with immunosuppressive agents such as cyclophosphamide or mycophenolate mofetil (MMF), or cyclosporine, systemic corticosteroids exposure within 90 days prior to start of LNP023/Placebo dosing
- Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
- All transplanted patients (any organ, including bone marrow)
- History of immunodeficiency diseases, or a positive HIV (ELISA and Western blot) test result.
- Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). A positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, excludes a patient. Patients with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded
Show all 38Show fewer
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject's medical history and/or clinical or laboratory evidence of any of the following:
- A history of invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
- Splenectomy
- Inflammatory bowel disease, peptic ulcers, severe gastrointestinal disorder including rectal bleeding;
- Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
- Pancreatic injury or pancreatitis;
- Liver disease or liver injury as indicated by abnormal liver function tests. ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase and serum bilirubin will be tested.
- Any single parameter of ALT, AST, GGT, alkaline phosphatase or serum bilirubin must not exceed 3 x upper limit of normal (ULN)
- PT/INR must be within the reference range of normal individuals
- Evidence of urinary obstruction or difficulty in voiding any urinary tract disorder other than IgNA that is associated with hematuria at screening and before dosing; [If necessary, laboratory testing may be repeated on one occasion (as soon as possible) prior to randomization, to rule out any laboratory error]
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline:
- PR > 200 msec
- QRS complex > 120 msec
- 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
- History of severe allergic reactions as per Investigator decision
- Plasma donation (> 200mL) within 30 days prior to first dosing.
- Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug. Highly effective contraception methods include:
- Total abstinence from heterosexual intercourse (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Female sterilization (have had 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.
- Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
- Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure <1%), for example hormone vaginal ring or transdermal hormone contraception 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 pregnancy, local regulations apply and will be described in the ICF.
- Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
- History of any porphyria metabolic disorder
- History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and baseline.
- History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes
Trial locations and contacts
56 sites in 25 countries.
56 sites in 25 countries
Japan5 sites
Novartis Investigative Site
Okayama, Okayama-ken, 700-8558
Novartis Investigative Site
Osaka, Osaka, 530-8480
Novartis Investigative Site
Sapporo, Hokkaido, 006-8555
Novartis Investigative Site
Sendai, Miyagi, 981-3205
Novartis Investigative Site
Toyoake, Aichi-ken, 470 1192
United Kingdom5 sites
Novartis Investigative Site
Cambridge, Cambrigdeshire, CB2 0QQ
Novartis Investigative Site
Leicester, LE5 4PW
Novartis Investigative Site
London, SE5 9RS
Novartis Investigative Site
Newcastle upon Tyne, NE7 7DN
Novartis Investigative Site
Salford, Manchester, M6 8HD
China4 sites
Novartis Investigative Site
Beijing, 100034
Novartis Investigative Site
Guangzhou, Guangdong, 510080
Novartis Investigative Site
Guangzhou, 510080
Novartis Investigative Site
Shanghai, 200040
Turkey (Türkiye)4 sites
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Istanbul, TUR, 34098
Novartis Investigative Site
Kocaeli, 41380
Novartis Investigative Site
Talas / Kayseri, 38039
Belgium3 sites
Novartis Investigative Site
Edegem, Antwerpen, 2650
Novartis Investigative Site
Leuven, 3000
Novartis Investigative Site
Roeselare, 8800
Israel3 sites
Novartis Investigative Site
Ashkelon, 78278
Novartis Investigative Site
Jerusalem, 9112001
Novartis Investigative Site
Petah Tikva, 49100
Norway3 sites
Novartis Investigative Site
Bergen, 5021
Novartis Investigative Site
Loerenskog, NO 1478
Novartis Investigative Site
Oslo, NO 0450
Taiwan3 sites
Novartis Investigative Site
New Taipei City, 23561
Novartis Investigative Site
Taichung, 40705
Novartis Investigative Site
Taipei, 10048
Argentina2 sites
Novartis Investigative Site
Caba, Buenos Aires, C1280AEB
Novartis Investigative Site
Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO
Australia2 sites
Novartis Investigative Site
Parkville, Victoria, 3050
Novartis Investigative Site
Westmead, New South Wales, 2145
Brazil2 sites
Novartis Investigative Site
Curitiba, Paraná, 80440-020
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90020-090
Denmark2 sites
Novartis Investigative Site
Aalborg, 9000
Novartis Investigative Site
Arhus N, DK-8200
Germany2 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Heidelberg, 69120
India2 sites
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110 017
Novartis Investigative Site
New Delhi, 110029
Singapore2 sites
Novartis Investigative Site
Singapore, 119228
Novartis Investigative Site
Singapore, 169608
Sweden2 sites
Novartis Investigative Site
Lund, 221 85
Novartis Investigative Site
Stockholm, 141 86
Thailand2 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10400
About this study
Official title: An Adaptive Seamless Randomized, Double-blind, Placebo-controlled, Dose Ranging Study to Investigate the Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
Efficacy and safety of LNP023 in IgAN patients
Read the detailed description
This was a multicenter, randomized, double-blind, dose-ranging, parallel-group study with an adaptive design (Part 1 informed the design adaptations for Part 2). In Part 1, three doses of LNP023 (10 mg, 50 mg, and 200 mg) vs. placebo control were compared; In Part 2, four doses of LNP023 (10 mg, 50 mg, 100 mg, and 200 mg) vs. placebo control were compared. The study comprised a run-in phase in order that patients were on stable and maximally tolerated dose of Angiotensin-converting-enzyme inhibitor (ACEi) or Angiotensin II Receptor Blockers (ARB) for at least 90 days, a 90 days treatment phase in Part 1; a 180 days treatment phase in Part 2 and a 90 days follow-up phase in both Parts 1 and 2.
- Conditions
- IgA Nephropathy
- Being tested
- LNP023, Placebo
- Keywords
- glomerunephritis, complement driven, chronic kidney disease
- Medical subject headings
- Glomerulonephritis, IGA, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LNP023Drug
LNP023 5, 25, 100 mg capsles
PlaceboOther
Matching placebo to LNP023
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo identical to LNP023 twice a day Receives: Other: Placebo |
| LNP023 10 mg BID | Experimental | 10 mg taken twice a day. Receives: Drug: LNP023 |
| LNP023 50 mg BID | Experimental | 50 mg taken twice a day. Receives: Drug: LNP023 |
| LNP023 100 mg BID - Part 2 | Experimental | 100 mg taken twice a day. Receives: Drug: LNP023 |
| LNP023 200 mg BID | Experimental | 200 mg taken twice a day. Receives: Drug: LNP023 |
What is being measured
The primary outcome is the main question the study is designed to answer.
MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90
The primary analysis of the dose-response effect of LNP023 versus placebo on the reduction in UPCR 24 hours at Day 90 was done using Multiple Comparison Procedure Modelling (MCP-Mod). The existence of a dose-response relationship was assessed at the MCP step at the one-sided 10% significance level vis a multiple contrasts test. In the Mod step, the mean predicted difference between each LNP023 dose and placebo were then estimated using parametric bootstrap model averaging. Results are presented on the original scale as geometric mean ratios. A ratio less than 1 indicates a reduction in proteinuria. Participants collected all urine over a 24 hour period for UPCR test.
Measured: Baseline and Day 90
Secondary outcomes (20)
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90
eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The CKD-EPI equation is an established, widely used and Kidney Disease Improving Global Outcomes (KDIGO) guideline recommended method of GFR estimation based on serum creatinine, age, gender and race of the patient. It was derived and validated established from a meta-analyses of multiple studies including large number of patients.
Measured: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90
Serum creatinine
Measured: Baseline and Day 90
Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90
Hematuria levels were the number of erythrocytes/high-power-field (hpf) measured through microscopic examination. The table shows the shift in hematuria grade (Low: <9 rbc/hpf, Intermediate: >=9 to <= 50 rbc/hpf, High: >50 rbc/hpf) from baseline (rows) to Day 90 (columns). A lower grade corresponds to a better outcome. Only patients with both baseline and Day 90 hematuria values are presented. L=low, I=intermediate and H=high in column headings for doses and BL=baseline
Measured: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90
Participants collected all of their urine over a 24-hour period.
Measured: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90
Participants collected all of their urine over a 24-hour period.
Measured: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90
Participants collected all of their urine over a 24-hour period.
Measured: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90
A midstream urine sample was obtained from the first morning void (FMV) on the visit day.
Measured: Baseline and Day 90
Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30
AUClast,ss: the area under the plasma concentration-time curve from time zero to last quantifiable concentration at steady state AUCtau,ss: the area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady state
Measured: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30
Cmax,ss: the observed maximum plasma concentration following drug administration at steady state (ng/mL) Ctrough,ss: the pre-dose plasma concentration observed during a dosing interval at steady state (ng/mL)
Measured: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30
Tmax,ss: the time to reach the maximum concentration after drug administration at steady state (h)
Measured: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30
Ae,ss: the total cumulative urinary excretion at steady state
Measured: Baseline and Day 30
Percent of LNP023 Excreted Into Urine at Day 30
Percent of drug excreted into the urine
Measured: Baseline and Day 30
Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30
The renal clearance from plasma at steady state
Measured: Baseline and Day 30
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90
The complement AP biomarkers Bb and sC5b-9 were evaluated as potential pharmacodynamics and mode-of-action markers. Both biomarkers were measured using validated enzyme-linked immunosorbent assays (ELISAs).
Measured: Baseline, Days 8, 15, 30, 60, 90
Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90
The table shows the ratio to baseline in UPCR at Day 90 by treatment group. The lowest dose providing maximal reduction of proteinuria is the dose with the smallest UPCR ratio to baseline estimate (i.e. LNP023 200mg),
Measured: Baseline up to Month 3
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180
eGFR; estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Measured: Baseline and Day 180
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180
A midstream urine sample was obtained from the first morning void (FMV) on the visit day.
Measured: Baseline and Day 180
Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180
Hematuria levels were the number of erythrocytes/high-power-field (hpf) measured through microscopic examination. The table shows the shift in hematuria grade (Low: <9 rbc/hpf, Intermediate: >=9 to <= 50 rbc/hpf, High: >50 rbc/hpf) from baseline (rows) to Day 180 (columns). A lower grade corresponds to a better outcome. Only patients with both baseline and Day 90 hematuria values are presented. L=low, I=intermediate and H=high in column headings for doses and BL=baseline
Measured: Baseline and Day 180
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180
For UPCR test, participants collected all of their urine over a 24-hour period
Measured: Baseline, Days 30, 90 and 180
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180
The 24-hour urine collection was started 1 day prior to the clinic visit, after participant urinated for the first time, than all urine was collected for the next 24 hours and refrigerated prior to clinic visit.
Measured: Baseline and Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2017
- Study start7 Feb 2018
- Primary completion29 Dec 2020
- Study completion22 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for IgA NephropathyStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03373461
- Sponsor's protocol ID
- CLNP023X2203
- Other IDs
- 2017-000891-27, 2017
- Status last verified
- Jan 2023
- First submitted
- 30 Nov 2017
- Last updated
- 30 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Rovin BH, Trimarchi H, Maes B, Perkovic V, Kashihara N, Zhang H, Barratt J, Cheng H, Lee H, Lee SH, Lim SK, Raju SB, Satirapoj B, Seyahi N, Tian YC, Wu CH, Xiong ZY, Xue H, Yee SY, Petrovic-Bulatovic K, Attari Z, Butylin D, Jacinto-Sanders S, Pletscher M, Magirr A, Renfurm R, Hach T, Rizk DV. Long-term efficacy and safety for the complement factor B inhibitor iptacopan in IgA nephropathy. Kidney Int. 2026 Oct 22:S0085-2538(26)00826-4. doi: 10.1016/j.kint.2026.09.017. Online ahead of print.
PubMed 42909451
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Adaptive Seamless Randomized, Double-blind, Placebo-controlled, Dose Ranging Study to Investigate the Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
- ClinicalTrials.gov ID
- NCT03373461
- Acronym / sponsor ID
- CLNP023X2203
- Conditions
- IgA Nephropathy
- Keywords
- glomerunephritis, complement driven, chronic kidney disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Feb 2018 (actual)
- Primary completion
- 29 Dec 2020 (actual)
- Study completion
- 22 Jun 2021 (actual)
- First posted
- 14 Dec 2017 (actual)
- Results
- Posted 7 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Efficacy and safety of LNP023 in IgAN patients
Detailed description
This was a multicenter, randomized, double-blind, dose-ranging, parallel-group study with an adaptive design (Part 1 informed the design adaptations for Part 2). In Part 1, three doses of LNP023 (10 mg, 50 mg, and 200 mg) vs. placebo control were compared; In Part 2, four doses of LNP023 (10 mg, 50 mg, 100 mg, and 200 mg) vs. placebo control were compared. The study comprised a run-in phase in order that patients were on stable and maximally tolerated dose of Angiotensin-converting-enzyme inhibitor (ACEi) or Angiotensin II Receptor Blockers (ARB) for at least 90 days, a 90 days treatment phase in Part 1; a 180 days treatment phase in Part 2 and a 90 days follow-up phase in both Parts 1 and 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboPlacebo identical to LNP023 twice a day |
| LNP023 10 mg BID | Experimental | Drug: LNP02310 mg taken twice a day. |
| LNP023 50 mg BID | Experimental | Drug: LNP02350 mg taken twice a day. |
| LNP023 100 mg BID - Part 2 | Experimental | Drug: LNP023100 mg taken twice a day. |
| LNP023 200 mg BID | Experimental | Drug: LNP023200 mg taken twice a day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Female and male patients above 18 years of age with a biopsy-verified IgA nephropathy and where the biopsy was performed within the prior three years.
- Patients must weigh at least 35 kg to participate in the study, and must have a body mass index (BMI) within the range of 15 - 38 kg/m2. BMI = Body weight (kg) / [Height (m)]2
- Measured Glomerular Filtration Rate (GFR) or estimated GFR (using the CKD-EPI formula) ≥30 mL/min per 1.73 m2
- Urine protein ≥1 g/24hr at screening and ≥0.75 g / 24h after the run- in period
- Vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 30 days prior to first dosing with LNP023. Vaccination against N. meningitidis type B, S. pneumoniae and H. influenzae should be conducted if available and acceptable by local regulations, at least 30 days prior to first dosing with LNP023
Key exclusion criteria (38 listed)
- Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy
- Patients previously treated with immunosuppressive agents such as cyclophosphamide or mycophenolate mofetil (MMF), or cyclosporine, systemic corticosteroids exposure within 90 days prior to start of LNP023/Placebo dosing
- Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
- All transplanted patients (any organ, including bone marrow)
- History of immunodeficiency diseases, or a positive HIV (ELISA and Western blot) test result.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LNP023LNP023 5, 25, 100 mg capsles | Drug | LNP023 10 mg BID, LNP023 100 mg BID - Part 2, LNP023 200 mg BID, LNP023 50 mg BID |
| PlaceboMatching placebo to LNP023 | Other | Placebo |
Primary outcome
MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90
Time frame: Baseline and Day 90
The primary analysis of the dose-response effect of LNP023 versus placebo on the reduction in UPCR 24 hours at Day 90 was done using Multiple Comparison Procedure Modelling (MCP-Mod). The existence of a dose-response relationship was assessed at the MCP step at the one-sided 10% significance level vis a multiple contrasts test. In the Mod step, the mean predicted difference between each LNP023 dose and placebo were then estimated using parametric bootstrap model averaging. Results are presented on the original scale as geometric mean ratios. A ratio less than 1 indicates a reduction in proteinuria. Participants collected all urine over a 24 hour period for UPCR test.
20 secondary outcomes
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90
Time frame: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90
Time frame: Baseline and Day 90
Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90
Time frame: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90
Time frame: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90
Time frame: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90
Time frame: Baseline and Day 90
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90
Time frame: Baseline and Day 90
Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30
Time frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30
Time frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30
Time frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30
Time frame: Baseline and Day 30
Percent of LNP023 Excreted Into Urine at Day 30
Time frame: Baseline and Day 30
Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30
Time frame: Baseline and Day 30
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90
Time frame: Baseline, Days 8, 15, 30, 60, 90
Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90
Time frame: Baseline up to Month 3
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180
Time frame: Baseline and Day 180
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180
Time frame: Baseline and Day 180
Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180
Time frame: Baseline and Day 180
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180
Time frame: Baseline, Days 30, 90 and 180
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180
Time frame: Baseline and Day 180
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42909451Rovin BH, Trimarchi H, Maes B, Perkovic V, Kashihara N, Zhang H, Barratt J, Cheng H, Lee H, Lee SH, Lim SK, Raju SB, Satirapoj B, Seyahi N, Tian YC, Wu CH, Xiong ZY, Xue H, Yee SY, Petrovic-Bulatovic K, Attari Z, Butylin D, Jacinto-Sanders S, Pletscher M, Magirr A, Renfurm R, Hach T, Rizk DV. Long-term efficacy and safety for the complement factor B inhibitor iptacopan in IgA nephropathy. Kidney Int. 2026 Oct 22:S0085-2538(26)00826-4. doi: 10.1016/j.kint.2026.09.017. Online ahead of print.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
56 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LNP023 in people with IgA Nephropathy, run by Novartis Pharmaceuticals at 56 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in Japan, United Kingdom, China, Turkey (Türkiye), Belgium and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90 (time frame: Baseline and Day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03373461, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2023.