GlomerulonephritisPhase 2NCT03832114
Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted
A Phase 2 study testing LNP023 in people with Glomerulonephritis, run by Novartis Pharmaceuticals at 9 sites in 6 countries.
Trial summary
The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glomerulonephritis
- What is being tested?
- LNP023
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 9 sitesin 6 countries
- Study dates
- 20 Feb 2019to 23 Apr 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
- Written informed consent must be obtained before any assessment is performed
- Male and female patients between the ages of 18 to 65 (inclusive) at screening
- C3G patients wit proteinuria
- Able to communicate well with the investigator, to understand and comply with the requirements of the study
- At screening and baseline visits, patients must weigh at least 35 kg
- Supine vital signs should be within the following ranges :
Show all 15Show fewer
- oral body temperature between 35.0-37.5 °C systolic blood pressure, 80-170 mm Hg diastolic blood pressure, 50-105 mm Hg pulse rate, 45 - 100 bpm
- .
- Estimated GFR (using the CKD-EPI formula) or measured GFR ≥30 mL/min per 1.73 m2 for patients on a maximum recommended or maximum tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)
- UPCR ≥ 100 mg/mmol (equivalent to ≥ 1 g/24h total urinary protein excretion)
- Prior to entry, all patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB for at least 30 days.
- No histological/laboratory/clinical signs of allorejection
- If applicable, induction treatment after allotransplantation needs to be completed >30 days before inclusion.
- Transplantation of a kidney allograft >90 days before inclusion
- Patients need to be on a stable dose of immunosuppressive regimen prior to inclusion. Any approved treatments are allowed for this purpose.
Who cannot join
- Use of other investigational drugs at the time of enrollment, or within 5 half-lives of randomization, or within 30 days, whichever is longer; or longer if required by local regulations
- A history of clinically significant ECG abnormalities,
- Known family history or known presence of long QT syndrome or Torsades de Pointes
- Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
- 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.
- 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.
Show all 9Show fewer
- History of immunodeficiency diseases, or a positive HIV test result.
- Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
- Patients who cannot receive vaccinations against N. meningitidis, S. pneumoniae, or H. influenzae
Trial locations and contacts
9 sites in 6 countries.
9 sites in 6 countries
France2 sites
Novartis Investigative Site
Montpellier, 34295
Novartis Investigative Site
Paris, 75015
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28041
United Kingdom2 sites
Novartis Investigative Site
London, W12 0NN
Novartis Investigative Site
Newcastle upon Tyne, NE7 7DN
About this study
Official title: An Open-label, Non-randomized Study on Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of LNP023 in Two Patient Populations With C3 Glomerulopathy
The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B).
- Conditions
- Glomerulonephritis
- Being tested
- LNP023
- Medical subject headings
- Glomerulonephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LNP023Drug
Increasing doses of LNP023 up to 200 mg.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A - no kidney transplant | Experimental | C3G patients who have not received a kidney transplant and have reduced C3 blood levels. Receives: Drug: LNP023 |
| Cohort B - kidney transplant | Experimental | C3G patients who have received a kidney transplant and have C3G recurrence. Receives: Drug: LNP023 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR)
Change in proteinuria assessed by ratio to baseline of UPCR derived from 24h urine collection
Measured: Week 12
Cohort B: Change From Baseline in C3 Deposit
Histopathological changes in kidney biopsies as assessed by change from baseline in C3 Deposit Score (based on immunofluorescence microscopy)
Measured: Week 12
Secondary outcomes (17)
Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR)
Ratio to baseline UPCR derived from 24 hour urine collection
Measured: Week 12: Day 84
Change From Baseline in Urine Protein (UP) Excretion
Ratio to baseline UP excretion derived from 24 hour urine collection
Measured: Week 12: Day 84
Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion
Ratio to baseline UACR excretion derived from 24 hour urine collection
Measured: Week 12: Day 84
Change From Baseline Change in Urinary Albumin (UA) Excretion
Ratio to baseline UA excretion derived from 24 hour urine collection
Measured: Week 12: Day 84
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Effect of LNP023 on estimated glomerular filtration rate (eGFR)
Measured: Day 84
Change From Baseline in Serum Creatinine
The effect of LNP023 on renal function - serum creatinine
Measured: Week 12: Day 84
Change From Baseline in Creatinine Clearance
The effect of LNP023 on renal function - creatinine clearance
Measured: Week 12: Day 84
Number of Patients With Hematuria
The effect of LNP023 on renal function - hematuria
Measured: Week 12: Day 84
Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) First Morning Void
Ratio to baseline of UPCR reduction derived from total cumulative urinary excretion first morning void
Measured: Week 9: Day 64
Change From Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR) First Morning Void
UACR reduction derived from total cumulative urinary excretion first morning void
Measured: Week 9: Day 64
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUClast (AUC)
The area under the plasma concentration-time curve calculated from time zero to the last quantifiable concentration point (hr*ng/mL)
Measured: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUCtau (AUC)
The area under the plasma concentration-time curve calculated to the end of the dosing interval (hr*ng/mL)
Measured: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Observed Maximum Concentration After Drug Administration (Cmax)
The observed maximum plasma concentration (ng/mL)
Measured: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Observed Minimum Concentration After Drug Administration (Ctrough)
The concentration that is just prior to the beginning of, or at the end, of a dosing interval (ng/mL)
Measured: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Time to Reach the Maximum Plasma Concentration (Tmax)
The time to reach peak or maximum concentration (hr)
Measured: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Summary of Change From Baseline Complement C3 Biomarker in Serum
To assess the effect of LNP023 on alternative complement pathway hyperactivity.
Measured: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84
Ratio to Baseline Summary of Plasma Bb
To assess the relationship between LNP023 dose and pharmacodynamic biomarker levels of blood Bb
Measured: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2019
- Study start20 Feb 2019
- Primary completion23 Apr 2021
- Study completion23 Apr 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 GlomerulonephritisStudies 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
- Non-randomised
- Intervention model
- Single group
- Model description
- The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B).
- Masking
- None (open label)
- Enrolment
- 27 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
- NCT03832114
- Sponsor's protocol ID
- CLNP023X2202
- Status last verified
- Jan 2024
- First submitted
- 28 Jan 2019
- Last updated
- 30 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- 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
Wong E, Nester C, Cavero T, Karras A, Le Quintrec M, Lightstone L, Eisenberger U, Soler MJ, Kavanagh D, Daina E, Praga M, Medjeral-Thomas NR, Gackler A, Garcia-Carro C, Biondani A, Chaperon F, Kulmatycki K, Milojevic J, Webb NJA, Nidamarthy PK, Junge G, Remuzzi G. Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy. Kidney Int Rep. 2023 Sep 22;8(12):2754-2764. doi: 10.1016/j.ekir.2023.09.017. eCollection 2023 Dec.
PubMed 38106570
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-randomized Study on Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of LNP023 in Two Patient Populations With C3 Glomerulopathy
- ClinicalTrials.gov ID
- NCT03832114
- Acronym / sponsor ID
- CLNP023X2202
- Conditions
- Glomerulonephritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Feb 2019 (actual)
- Primary completion
- 23 Apr 2021 (actual)
- Study completion
- 23 Apr 2021 (actual)
- First posted
- 6 Feb 2019 (actual)
- Results
- Posted 8 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B).
| Arm | Type | Receives |
|---|---|---|
| Cohort A - no kidney transplant | Experimental | Drug: LNP023C3G patients who have not received a kidney transplant and have reduced C3 blood levels. |
| Cohort B - kidney transplant | Experimental | Drug: LNP023C3G patients who have received a kidney transplant and have C3G recurrence. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Written informed consent must be obtained before any assessment is performed
- Male and female patients between the ages of 18 to 65 (inclusive) at screening
- C3G patients wit proteinuria
- Able to communicate well with the investigator, to understand and comply with the requirements of the study
- At screening and baseline visits, patients must weigh at least 35 kg
Key exclusion criteria (9 listed)
- Use of other investigational drugs at the time of enrollment, or within 5 half-lives of randomization, or within 30 days, whichever is longer; or longer if required by local regulations
- A history of clinically significant ECG abnormalities,
- Known family history or known presence of long QT syndrome or Torsades de Pointes
- Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
- 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.
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 |
|---|---|---|
| LNP023Increasing doses of LNP023 up to 200 mg. | Drug | Cohort A - no kidney transplant, Cohort B - kidney transplant |
Primary outcome
Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR)
Time frame: Week 12
Change in proteinuria assessed by ratio to baseline of UPCR derived from 24h urine collection
Cohort B: Change From Baseline in C3 Deposit
Time frame: Week 12
Histopathological changes in kidney biopsies as assessed by change from baseline in C3 Deposit Score (based on immunofluorescence microscopy)
17 secondary outcomes
Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR)
Time frame: Week 12: Day 84
Change From Baseline in Urine Protein (UP) Excretion
Time frame: Week 12: Day 84
Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion
Time frame: Week 12: Day 84
Change From Baseline Change in Urinary Albumin (UA) Excretion
Time frame: Week 12: Day 84
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Day 84
Change From Baseline in Serum Creatinine
Time frame: Week 12: Day 84
Change From Baseline in Creatinine Clearance
Time frame: Week 12: Day 84
Number of Patients With Hematuria
Time frame: Week 12: Day 84
Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) First Morning Void
Time frame: Week 9: Day 64
Change From Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR) First Morning Void
Time frame: Week 9: Day 64
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUClast (AUC)
Time frame: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Pharmacokinetics of LNP023 Area Under the Plasma-concentration-time Curve AUCtau (AUC)
Time frame: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Observed Maximum Concentration After Drug Administration (Cmax)
Time frame: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Observed Minimum Concentration After Drug Administration (Ctrough)
Time frame: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Time to Reach the Maximum Plasma Concentration (Tmax)
Time frame: Day 7, Day 14, Day 21, Day 28 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h post dose) and Day 36, Day 64 and Day 84 (pre-dose)
Summary of Change From Baseline Complement C3 Biomarker in Serum
Time frame: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84
Ratio to Baseline Summary of Plasma Bb
Time frame: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Day 36, Day 64, Day 84
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38106570Wong E, Nester C, Cavero T, Karras A, Le Quintrec M, Lightstone L, Eisenberger U, Soler MJ, Kavanagh D, Daina E, Praga M, Medjeral-Thomas NR, Gackler A, Garcia-Carro C, Biondani A, Chaperon F, Kulmatycki K, Milojevic J, Webb NJA, Nidamarthy PK, Junge G, Remuzzi G. Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy. Kidney Int Rep. 2023 Sep 22;8(12):2754-2764. doi: 10.1016/j.ekir.2023.09.017. eCollection 2023 Dec.
- Link to plain language trial summaryLink 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
Related trials for Glomerulonephritis
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
RecruitingPhase 4
Dapagliflozin in Active Lupus Nephritis
Lupus Nephritis (LN)
RecruitingPhase 3
A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
Focal Segmental Glomerulosclerosis
Not yet recruitingPhase 3
A Study to Assess the Efficacy and Safety of Pegcetacoplan for the Prevention of Recurrent C3G or Primary IC-MPGN in Kidney Transplant Recipients
C3 Glomerulopathy (C3G), Primary Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN), Recurrent Glomerular Disease After Kidney Transplantation
Not yet recruiting
MYTP01 for Immune-Mediated Diseases
IgA Nephropathy, Kidney Transplant Recipients
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.
9 sites in 6 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 Glomerulonephritis, run by Novartis Pharmaceuticals at 9 sites in 6 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 15 inclusion and 9 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 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, Spain, United Kingdom, United States, Germany and 1 more country. 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. 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 8 Jul 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?
Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR) (time frame: Week 12). The study lists 2 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 NCT03832114, 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 2024.