E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021263 |
E.1.2 | Term | IgA nephropathy |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate superiority of LNP023 vs. placebo in the reduction of proteinuria at 9 months by measuring UPCR sampled from a 24h urine collection.
To demonstrate superiority of LNP023 vs. placebo in slowing renal disease progression measured by the annualized total slope of Estimated Glomerular Filtration Rate (eGFR) decline over 24 months. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of LNP023 vs. placebo on the proportion of study participants reaching proteinuria below 1g/g of UPCR (sampled from 24h urine collection) at 9 months; To evaluate the effect of LNP023 vs. placebo on slowing renal disease progression measured by the annualized total slope of eGFR decline over 1 year; To assess the effect of LNP023 vs. placebo on the change from baseline to 9 months in fatigue scale measured by the FACIT-Fatigue questionnaire; To demonstrate the superiority of LNP023 vs. placebo on: delaying the time to first occurrence of a composite renal endpoint of reaching either at least 30% decline in eGFR, ESRD or renal death; in the reduction of proteinuria by measuring UPCR sampled from a 24h urine collection; on the proportion of study participants reaching proteinuria below 1g/g of UPCR (sampled from 24h urine collection) at 9 months; on the change from baseline to 9 months in the fatigue scale measured by FACIT-Fatigue questionnaire |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
optional genetic research component |
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E.3 | Principal inclusion criteria |
•Male and female patients ≥ 18 years of age with an eGFR level and biopsy-confirmed IgA nephropathy as follows:
•For patients eGFR* ≥ 45ml/min/1.73m2, a qualifying biopsy performed within the last 5 years is required.
•For patients with eGFR* 30 to <45ml/min/1.73m2 a qualifying biopsy performed within 2 years with < 50% tubulointerstitial fibrosis is required.
• For patients with eGFR* 20 to <30ml/min/1.73m2,a qualifying biopsy performed at any time.
In all cases, if a historical biopsy is not available, one may be performed during screening. *eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines)
•Proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening by UPCR ≥1 g/g (113 mg/mmol) sampled from FMV or 24h urine collection, as well as at the completion of the run-in period by UPCR ≥1 g/g (113 mg/mmol) calculated as the mean of two 24h urine collections obtained within 14 days of each other at baseline.
•Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
•If not previously vaccinated, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
•All patients must have been on supportive care including stable dose regimen of ACEi or ARB at either the locally approved maximal daily dose or the maximally tolerated dose (per investigators’ judgment) for at least 90 days before first study drug administration. In addition, if patients are taking diuretics or other antihypertensive therapy, the doses should also be stabilized for at least 90 days prior to the first dosing of study treatment.
Other protocol-defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
•Any secondary IgAN as defined by the investigator; secondary IgAN can be associated with cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, and inflammatory bowel disease, familial mediterranean fever, etc.
•Sitting office SBP >140 mmHg or DBP >90 mmHg at the randomization visit
• Patients previously treated with immunosuppressive or other immunmodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, hydroxychloroquine, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids exposure (>10 mg/d prednisone/prednisolone equivalent) within 90 days (or 180 days for rituximab) prior to first study drug administration
•Prior use of LNP023 or prior enrollment in any other LNP023 clinical trial where study drug was taken, including matching placebo
•History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.
•Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study drug administration.
Other protocol-defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Log-transformed ratio to baseline in UPCR (sampled from 24h urine collection) at 9 months
- Annualized total Estimated Glomerular Filtration Rate (eGFR) slope estimated over 24 months). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline and 9 months
baseline and 24 months |
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E.5.2 | Secondary end point(s) |
-Proportion of participants reaching Urine Protein To Creatinine Ratio <1g/g at 9 months, without receiving Corticosteroids/ Immunosuppressant or other newly approved drugs for treatment of IgAN or initiating Renal Replacement Therapy.
-Annualized total Estimated Glomerular Filtration Rate slope estimated over 12 months
- Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire
- Time from randomization to first occurrence of composite renal endpoint event, defined as reaching either ≥30% decline in Estimated Glomerular Filtration Rate (eGFR) relative to baseline, or End Stage Renal Disease (ESRD), or renal death
-Log-transformed ratio to baseline in Urine Protein-To-Creatinine Ratio (sampled from 24h urine collection)
-Proportion of participants reaching Urine Protein-To-Creatinine Ratio <1g/g at 9 months without receiving Corticosteroids/ Immunosuppressant Therapy or other newly approved drugs for treatment of IgAN or initiating renal replacement therapy
-Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline and 9 months
Baseline and 12 months
baseline and 9 months
up to 24 months
24 months
baseline and 24 months
baseline and 24 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
China |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
Norway |
Russian Federation |
Singapore |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
Vietnam |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 5 |