C3GPhase 3APPEAR-C3GNCT04817618
Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.
A Phase 3 study testing iptacopan in people with C3G, run by Novartis Pharmaceuticals at 88 sites in 19 countries.
Trial summary
The Primary Completion Date and Study Completion Date have been updated to reflect completion of the adolescent cohort, which has been added to the protocol. The study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan… Read more about this study
- Who is it for?
- Ages 12 to 60 years
- Conditions the study is for
- C3G
- What is being tested?
- iptacopan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 88 sitesin 19 countries
- Study dates
- 28 Jul 2021to 29 Jan 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 12 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male and female participants age ≥ 12 and ≤ 60 years at screening.
- Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment in adults and within 3 years in adolescents.
- 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 acid, 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 for ages ≥ 18 years and modified Schwartz formula for ages 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 prior to the start of study treatment.
- 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 study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
Who cannot join
- Participants who have received any cell or organ transplantation, including a 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
- The presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration.
Show all 10Show fewer
- A history of recurrent invasive infections caused by encapsulated organisms, e.g., N. meningitidis and S. pneumoniae.
- The use of inhibitors of complement factors (e.g., Factor B, Factor D, C3 inhibitors, anti 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.
- Acute post-infectious glomerulonephritis at screening based upon the opinion of the investigator.
Trial locations and contacts
88 sites in 19 countries. Contact the study team or a site near you to ask about taking part.
Novartis Pharmaceuticals contact
88 sites in 19 countries
United States13 sites, 4 recruiting
- Withdrawn
Albany Medical Center
Albany, New York, 12208
- Recruiting
Childrens Hospital Colorado
Aurora, Colorado, 80045
Kati Dugan, +1 720 777 1234, Kati.Dugan@childrenscolorado.org
Bradley Dixon
- Withdrawn
Johns Hopkins Hospital
Baltimore, Maryland, 21287
- Withdrawn
Brigham and Womens Hosp Harvard Med School
Boston, Massachusetts, 02115
- Withdrawn
Hackensack Uni Medical Center
Hackensack, New Jersey, 07601
- Withdrawn
IN University School of Med
Indianapolis, Indiana, 46202-5111
- Recruiting
University of Iowa Health Care
Iowa City, Iowa, 52242-1091
Nicole Gerot, +1 319 335 7555, nicole-gerot@uiowa.edu
Carla Nester
- Recruiting
University of Iowa Health Care
Iowa City, Iowa, 52242
Nikki Gerot, +1 (319) 335-0348
Carla Nester
- Completed
Georgia Nephrology Research Inst
Lawrenceville, Georgia, 30046
- Withdrawn
University of Wisconsin
Madison, Wisconsin, 53792
- Recruiting
Nicklaus Childrens Hospital
Miami, Florida, 33155
Moya Chang, +1 305 661 1515, Moya.chang@nicklaushealth.org
Ana Paredes
- Completed
Col Uni Med Center New York Presby
New York, New York, 10032
- Withdrawn
Baylor Scott and White Research
Temple, Texas, 76502
Brazil9 sites, 3 recruiting
- Withdrawn
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30150-221
- Withdrawn
Novartis Investigative Site
Joinville, Santa Catarina, 89227-680
- Withdrawn
Novartis Investigative Site
Passo Fundo, Rio Grande do Sul, 99010-260
- Recruiting
Novartis Investigative Site
Recife, Pernambuco, 50740-900
- Withdrawn
Novartis Investigative Site
Salvador, 40323-010
- Withdrawn
Novartis Investigative Site
Santo André, São Paulo, 09090-790
- Recruiting
Novartis Investigative Site
São Paulo, São Paulo, 04038-002
- Withdrawn
Novartis Investigative Site
São Paulo, São Paulo, 05403-000
- Recruiting
Novartis Investigative Site
São Paulo, São Paulo, 05403-000
Germany8 sites
- Withdrawn
Novartis Investigative Site
Aachen, 52074
- Active, not recruiting
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 50937
- Completed
Novartis Investigative Site
Erlangen, 91054
- Completed
Novartis Investigative Site
Essen, 45147
- Completed
Novartis Investigative Site
Hamburg, 20246
- Withdrawn
Novartis Investigative Site
Hanover, 30625
- Active, not recruiting
Novartis Investigative Site
Heidelberg, 69120
- Completed
Novartis Investigative Site
Mainz, 55131
Japan6 sites
- Completed
Novartis Investigative Site
Asahikawa, Hokkaido, 0788510
- Completed
Novartis Investigative Site
Nagoya, Aichi-ken, 4668560
- Completed
Novartis Investigative Site
Niigata, 9518520
- Completed
Novartis Investigative Site
Ōtsu, Shiga, 520-2192
- Completed
Novartis Investigative Site
Sapporo, Hokkaido, 0608543
- Completed
Novartis Investigative Site
Takatsuki, Osaka, 5691192
Spain6 sites
- Withdrawn
Novartis Investigative Site
Barcelona, Catalonia, 08025
- Withdrawn
Novartis Investigative Site
Barcelona, 08035
- Completed
Novartis Investigative Site
Madrid, 28041
- Withdrawn
Novartis Investigative Site
Málaga, 29010
- Withdrawn
Novartis Investigative Site
Port de Sagunt, Valencia, 46520
- Completed
Novartis Investigative Site
Seville, 41009
China5 sites, 1 recruiting
- Active, not recruiting
Novartis Investigative Site
Beijing, 100034
- Recruiting
Novartis Investigative Site
Beijing, 100730
- Active, not recruiting
Novartis Investigative Site
Guangzhou, Guangdong, 510080
- Active, not recruiting
Novartis Investigative Site
Shanghai, 200040
- Withdrawn
Novartis Investigative Site
Wuhan, Hubei, 430022
France5 sites
- Completed
Novartis Investigative Site
Lille, 59037
- Withdrawn
Novartis Investigative Site
Marseille, 13005
- Withdrawn
Novartis Investigative Site
Montpellier, 34295
- Completed
Novartis Investigative Site
Paris, 75015
- Withdrawn
Novartis Investigative Site
Paris, 75019
India5 sites
- Withdrawn
Novartis Investigative Site
Dehradun, Uttarakhand, 248001
- Withdrawn
Novartis Investigative Site
Hyderabad, Telangana, 500058
- Active, not recruiting
Novartis Investigative Site
Lucknow, Uttar Pradesh, 226014
- Active, not recruiting
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110017
- Active, not recruiting
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110029
Turkey (Türkiye)5 sites
- Completed
Novartis Investigative Site
Ankara, Yenimahalle, 06500
- Withdrawn
Novartis Investigative Site
Ankara, Yenimahalle, 06500
- Withdrawn
Novartis Investigative Site
Istanbul, Fatih, 34093
- Withdrawn
Novartis Investigative Site
Istanbul, Fatih, 34098
- Completed
Novartis Investigative Site
Kayseri, Melikgazi, 38039
Greece4 sites
- Withdrawn
Novartis Investigative Site
Athens, 115 27
- Completed
Novartis Investigative Site
Heraklion Crete., 715 00
- Completed
Novartis Investigative Site
Thessaloniki, 546 42
- Withdrawn
Novartis Investigative Site
Thessaloniki, 546 42
United Kingdom4 sites
- Withdrawn
Novartis Investigative Site
Glasgow, Scotland, G51 4TF
- Completed
Novartis Investigative Site
London, W12 0HS
- Active, not recruiting
Novartis Investigative Site
London, WC1N 3JH
- Active, not recruiting
Novartis Investigative Site
Newcastle upon Tyne, Tyne and Wear, NE1 4LP
Argentina3 sites
- Completed
Novartis Investigative Site
Buenos Aires, W3400ABH
- Withdrawn
Novartis Investigative Site
CABA, C1181ACH
- Withdrawn
Novartis Investigative Site
Córdoba, Córdoba Province, X5016KET
Canada3 sites
- Completed
Novartis Investigative Site
London, Ontario, N6A 5W9
- Withdrawn
Novartis Investigative Site
Montreal, Quebec, H3T 1C5
- Completed
Novartis Investigative Site
Toronto, Ontario, M5G 2C4
Italy3 sites
- Withdrawn
Novartis Investigative Site
Milan, MI, 20122
- Completed
Novartis Investigative Site
Ranica, BG, 24020
- Completed
Novartis Investigative Site
Roma, RM, 00165
Belgium2 sites
- Withdrawn
Novartis Investigative Site
Edegem, 2650
- Withdrawn
Novartis Investigative Site
Leuven, 3000
Israel2 sites
- Completed
Novartis Investigative Site
Petah Tikva, 4920235
- Completed
Novartis Investigative Site
Petah Tikva, 4941492
Netherlands2 sites
- Completed
Novartis Investigative Site
Leiden, South Holland, 2333 ZA
- Withdrawn
Novartis Investigative Site
Nijmegen, 6525 GA
Switzerland2 sites
- Completed
Novartis Investigative Site
Bern, 3010
- Withdrawn
Novartis Investigative Site
Lausanne, 1011
About this study
Official title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Iptacopan (LNP023) in Complement 3 Glomerulopathy.
The Primary Completion Date and Study Completion Date have been updated to reflect completion of the adolescent cohort, which has been added to the protocol.
The study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in complement 3 glomerulopathy.
Read the detailed description
The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to placebo and standard of care in patients with native C3G. CLNP023B12301 is a Phase 3 pivotal trial for registration of iptacopan in C3G. The study aims to determine the reduction in UPCR and improvement in eGFR in participants treated with iptacopan compared to placebo, as well as the proportion of participants who achieve a composite renal endpoint consisting of eGFR and UPCR elements. These effects of iptacopan in conjunction with increases in serum C3 levels will provide support for an iptacopan profile that includes stabilization of eGFR, clinically meaningful reductions in proteinuria and inhibition of the complement AP. Kidney biopsies will be performed in adult participants to evaluate histopathological improvements in immunofluorescence and light microscopy that support these functional benefits of iptacopan.
- Conditions
- C3G
- Being tested
- Placebo, iptacopan
- Keywords
- LNP023, iptacopan, C3G, UPCR, eGFR, proteinuria, Quality of life
- Medical subject headings
- Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo to iptacopan 200mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)
iptacopanDrug
Also called LNP023
iptacopan 200 mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)
| Study group | Role | What they receive |
|---|---|---|
| iptacopan 200mg | Experimental | iptacopan 200 mg b.i.d. Receives: Drug: iptacopan |
| Placebo to iptacopan 200mg | Placebo comparator | Placebo to iptacopan 200mg b.i.d. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adult cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months of treatment.
Measured: 6 months (double-blind)
Adolescent cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)
To evaluate the effect of iptacopan on proteinuria at 6 months.
Measured: 6 months (double-blind)
Change from baseline in log-transformed UPCR at the 12-month visit (both study treatment arms).
To evaluate the effect of iptacopan on proteinuria at 12 months.
Measured: 12 months (double-blind and open-label)
Change in log-transformed UPCR from the 6-month visit to the 12-month visit in the placebo arm
To evaluate the effect of iptacopan on proteinuria at 12 months.
Measured: From month 6 to month 12 (open-label)
Secondary outcomes (14)
Change from baseline in eGFR.
To demonstrate the superiority of iptacopan vs. placebo in improving eGFR.
Measured: 6 months (double-blind)
Proportion of participants who meet the criteria for achieving a composite renal endpoint
To demonstrate the superiority of iptacopan vs. placebo in the proportion of participants who meet the criteria for achieving a composite renal endpoint.
A participant meets the requirements of the composite renal endpoint if he/she satisfies: (1) a stable or improved eGFR compared to the baseline visit (≤15% reduction in eGFR), and (2) a ≥50% reduction in UPCR compared to the baseline visit.
Measured: 6 months (double-blind)
Adult cohort: Change from baseline in disease total activity score in a renal biopsy.
To demonstrate the effect of iptacopan vs placebo in reducing glomerular inflammation in the kidney.
Measured: 6 months (double-blind)
Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.
To assess the effect of iptacopan compared to placebo in improvement of patient reported fatigue.
Measured: 6 months (double-blind)
Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements
To evaluate the safety and tolerability of iptacopan compared to placebo.
Measured: 6 months (double-blind)
Number of participants with study drug discontinuation due to an AE
To evaluate the safety and tolerability of iptacopan compared to placebo
Measured: 6 months (double-blind)
Proportion of participants who meet the criteria for achieving a composite renal endpoint
To evaluate the effect at 12 months of iptacopan on a composite renal endpoint. A participant meets the requirements of the composite renal endpoint if he/she satisfies: (1) a stable or improved eGFR compared to the baseline visit (≤15% reduction in eGFR), and (2) a ≥50% reduction in UPCR compared to the baseline visit.
Measured: 12 months (double-blind and open-label)
Proportion of patients achieving a composite renal endpoint from the 6-month visit to the 12-month visit of the placebo arm
To evaluate the effect at 12 months of iptacopan on a composite renal endpoint. A participant meets the requirements of the composite renal endpoint if he/she satisfies: (1) a stable or improved eGFR compared to the baseline visit (≤15% reduction in eGFR), and (2) a ≥50% reduction in UPCR compared to the 6 months visit.
Measured: month 6, month 12 (open-label)
Change from baseline in the total activity score in a renal biopsy at 12 months
To evaluate the effect at 12 months of iptacopan in reducing glomerular inflammation in the kidney.
Measured: Baseline, month 12 (double-blind and open-label)
Change in the total activity score in a renal biopsy from the 6-month visit to the 12-month visit of the placebo arm.
To evaluate the effect at 12 months of iptacopan in reducing glomerular inflammation in the kidney.
Measured: month 6, month 12 (open-label)
Change from baseline in the FACIT-Fatigue score at 12 months
To evaluate the effect at 12 months of iptacopan in improvement of patient reported fatigue
Measured: Baseline, month 12 (double-blind and open-label)
Change in the FACIT-Fatigue score from the 6-month visit to the 12-month visit of the placebo arm
To evaluate the effect at 12 months of iptacopan in improvement of patient reported fatigue
Measured: month 6, month 12 (open-label)
Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements
To evaluate the safety and tolerability of iptacopan during the 6-month open-label treatment period as well as the entire 12- month treatment period
Measured: 12 months (double-blind and open-label)
Number of participants with study drug discontinuation due to an AE
To evaluate the safety and tolerability of iptacopan during the 6-month open-label treatment period as well as the entire 12- month treatment period.
Measured: 12 months (double-blind and open-label)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2021
- Study start28 Jul 2021
- Primary completion29 Jan 2027 (estimated)
- Study completion29 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for C3GStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 98 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04817618
- Sponsor's protocol ID
- CLNP023B12301
- Other IDs
- 2020-004589-21
- Acronym
- APPEAR-C3G
- Status last verified
- Nov 2026
- First submitted
- 23 Mar 2021
- Last updated
- 5 Nov 2026
- Results posted
- No
- 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
Kavanagh D, Bomback AS, Vivarelli M, Nester CM, Remuzzi G, Zhao MH, Wong EKS, Wang Y, Krishnan I, Schuhmann I, Trapani AJ, Webb NJA, Meier M, Israni RK, Smith RJH; APPEAR-C3G investigators. Oral iptacopan therapy in patients with C3 glomerulopathy: a randomised, double-blind, parallel group, multicentre, placebo-controlled, phase 3 study. Lancet. 2025 Oct 11;406(10512):1587-1598. doi: 10.1016/S0140-6736(25)01148-1. Epub 2025 Sep 25.
PubMed 41016405
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Iptacopan (LNP023) in Complement 3 Glomerulopathy.
- ClinicalTrials.gov ID
- NCT04817618
- Acronym / sponsor ID
- APPEAR-C3G / CLNP023B12301
- Conditions
- C3G
- Keywords
- LNP023, iptacopan, C3G, UPCR, eGFR, proteinuria, Quality of life
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 98 participants (estimated)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 28 Jul 2021 (actual)
- Primary completion
- 29 Jan 2027 (estimated)
- Study completion
- 29 Jan 2027 (estimated)
- First posted
- 26 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Primary Completion Date and Study Completion Date have been updated to reflect completion of the adolescent cohort, which has been added to the protocol.
The study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in complement 3 glomerulopathy.
Detailed description
The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to placebo and standard of care in patients with native C3G. CLNP023B12301 is a Phase 3 pivotal trial for registration of iptacopan in C3G. The study aims to determine the reduction in UPCR and improvement in eGFR in participants treated with iptacopan compared to placebo, as well as the proportion of participants who achieve a composite renal endpoint consisting of eGFR and UPCR elements. These effects of iptacopan in conjunction with increases in serum C3 levels will provide support for an iptacopan profile that includes stabilization of eGFR, clinically meaningful reductions in proteinuria and inhibition of the complement AP. Kidney biopsies will be performed in adult participants to evaluate histopathological improvements in immunofluorescence and light microscopy that support these functional benefits of iptacopan.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| iptacopan 200mg | Experimental | Drug: iptacopaniptacopan 200 mg b.i.d. |
| Placebo to iptacopan 200mg | Placebo comparator | Drug: PlaceboPlacebo to iptacopan 200mg b.i.d. |
Who may qualify
- Ages
- 12 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Male and female participants age ≥ 12 and ≤ 60 years at screening.
- Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment in adults and within 3 years in adolescents.
- 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 acid, 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.
Key exclusion criteria (10 listed)
- Participants who have received any cell or organ transplantation, including a 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
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 |
|---|---|---|
| PlaceboPlacebo to iptacopan 200mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d) | Drug | Placebo to iptacopan 200mg |
| iptacopanAlso: LNP023iptacopan 200 mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d) | Drug | iptacopan 200mg |
Primary outcome
Adult cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)
Time frame: 6 months (double-blind)
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months of treatment.
Adolescent cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)
Time frame: 6 months (double-blind)
To evaluate the effect of iptacopan on proteinuria at 6 months.
Change from baseline in log-transformed UPCR at the 12-month visit (both study treatment arms).
Time frame: 12 months (double-blind and open-label)
To evaluate the effect of iptacopan on proteinuria at 12 months.
Change in log-transformed UPCR from the 6-month visit to the 12-month visit in the placebo arm
Time frame: From month 6 to month 12 (open-label)
To evaluate the effect of iptacopan on proteinuria at 12 months.
14 secondary outcomes
Change from baseline in eGFR.
Time frame: 6 months (double-blind)
Proportion of participants who meet the criteria for achieving a composite renal endpoint
Time frame: 6 months (double-blind)
Adult cohort: Change from baseline in disease total activity score in a renal biopsy.
Time frame: 6 months (double-blind)
Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.
Time frame: 6 months (double-blind)
Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements
Time frame: 6 months (double-blind)
Number of participants with study drug discontinuation due to an AE
Time frame: 6 months (double-blind)
Proportion of participants who meet the criteria for achieving a composite renal endpoint
Time frame: 12 months (double-blind and open-label)
Proportion of patients achieving a composite renal endpoint from the 6-month visit to the 12-month visit of the placebo arm
Time frame: month 6, month 12 (open-label)
Change from baseline in the total activity score in a renal biopsy at 12 months
Time frame: Baseline, month 12 (double-blind and open-label)
Change in the total activity score in a renal biopsy from the 6-month visit to the 12-month visit of the placebo arm.
Time frame: month 6, month 12 (open-label)
Change from baseline in the FACIT-Fatigue score at 12 months
Time frame: Baseline, month 12 (double-blind and open-label)
Change in the FACIT-Fatigue score from the 6-month visit to the 12-month visit of the placebo arm
Time frame: month 6, month 12 (open-label)
Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements
Time frame: 12 months (double-blind and open-label)
Number of participants with study drug discontinuation due to an AE
Time frame: 12 months (double-blind and open-label)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Derived from this study: PubMed 41016405Kavanagh D, Bomback AS, Vivarelli M, Nester CM, Remuzzi G, Zhao MH, Wong EKS, Wang Y, Krishnan I, Schuhmann I, Trapani AJ, Webb NJA, Meier M, Israni RK, Smith RJH; APPEAR-C3G investigators. Oral iptacopan therapy in patients with C3 glomerulopathy: a randomised, double-blind, parallel group, multicentre, placebo-controlled, phase 3 study. Lancet. 2025 Oct 11;406(10512):1587-1598. doi: 10.1016/S0140-6736(25)01148-1. Epub 2025 Sep 25.
- 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.
Novartis Pharmaceuticals contact
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
88 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing iptacopan in people with C3G, run by Novartis Pharmaceuticals at 88 sites in 19 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 8 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 88 sites in United States, Brazil, Germany, Japan, Spain and 14 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Novartis Pharmaceuticals (1-888-669-6682, novartis.email@novartis.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adult cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) (time frame: 6 months (double-blind)). The study lists 4 primary outcomes in all. 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 NCT04817618, 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 5 Nov 2026.