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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•Primary Efficacy Objective: To characterize the effect of treatment with LNP023 on a 3-component composite renal response endpoint at the 9-month visit
•Primary Safety Objective: To evaluate the long-term safety and
tolerability of LNP023 in participants with C3G |
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E.2.2 | Secondary objectives of the trial |
•To characterize the effect of treatment with LNP023 on a 2-component composite renal response endpoint at the 9-month visit
•To assess the long-term effect of LNP023 on renal function in C3G
participants at the 9-month visit
• To assess the effect of LNP023 on proteinuria in C3G participants at
the 3-month visit
•To describe the status of C3G disease progression based on glomerular histopathology in a renal biopsy at the 6 to9-month visit
•To evaluate the long-term effect of LNP023 on specific components of the complement pathway at the 9-month visit •To assess the long-term effect of LNP023 on urine markers of renal
damage at the 9-month visit
•To assess the longer term(>9 months and up to36 months of
treatment in CLNP023B12001B)effects of LNP023 on the composite
renal response endpoint,renal function,renal histopathology and
specific components of the complement pathway in C3G participants
•To evaluate pharmacokinetics of LNP023 in participants under
prolonged treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must have completed the treatment period of the CLNP023X2202 trial on study drug. |
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E.4 | Principal exclusion criteria |
•Severe concurrent co-morbidities, e.g. advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), or any illness or medical condition that in the opinion of the investigator and sponsor is likely to prevent the patient from safely tolerating LNP023 or complying with the requirements of the study.
•Participants with an active systemic bacterial, viral or fungal infection
within 14 days prior to screening, or
The presence of fever ≥ 38oC (100.4oF) within 7 days prior to screening.
•History of human immunodeficiency virus (HIV) or any other
immunodeficiency disease.
•History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants. |
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E.5 End points |
E.5.1 | Primary end point(s) |
•A participant is defined as a responder for the composite renal
response endpoint if they meet the following criteria at the 9-month visit in LNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2)
either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., ≥ the lower limit of normal (LLN)). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a non-responder.
•Occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
•9-month visit
•9-month visit, end of study |
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E.5.2 | Secondary end point(s) |
•A participant is defined as a responder if they meet the following
criteria at the 9-month visit in CLNP023B12001B: (1) a stable or
improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥ 50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., LLN). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the. Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a non-responder.
•Change from baseline in log-transformed urine protein/creatinine ratio (UPCR), change from baseline in log-transformed urine albumin/creatinine ratio (UACR), change from baseline in serum creatinine concentration and change from baseline in estimated glomerular filtration rate (eGFR) at the 9 month visit in CLNP023B12001B.
• Change from baseline in log-transformed urine protein/creatinine ratio (UPCR) and change from baseline in log-transformed urine
albumin/creatinine ratio (UACR), at the 3-month visit in
CLNP023B12001B.
•C3 deposit score, disease activity and chronicity scores from a renal biopsy at 6 to 9 months from entry to the CLNP023B12001B study. Biopsies will be compared to those obtained in the CLNP023X2202 study (if available).
•Change from baseline in circulating levels of complement components C3 (serum), change from baseline in Bb (plasma) and change from baseline in sC5b-9 (plasma) at the 9 months visit in CLNP023B12001B.
•Change from baseline in urinary kidney biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) at the 9 months visit in CLNP023B12001B compared to the baseline visit in CLNP023X2202.
•A participant is defined as a responder for the composite renal response endpoint if they meet the following criteria at times >9 months and up to 36 months in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) an increase in C3 to ≥80% (i.e., ≥72mg/dL or 0.72 g/L) of the lower limit of normal (LLN, 90 mg/dL or 0.9 g/L). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the subject as a non-responder.
•Change from baseline in log-transformed UPCR, log-transformed UACR, serum creatinine concentration and estimated glomerular filtration rate (eGFR) at times >9 months and up to 36 months in CLNP023B12001B.
•Change in C3 deposit score, disease activity and chronicity scores from a renal biopsy at times >9 months and up to 36 months from entry to the CLNP023B12001B study.
•Change from baseline in circulating levels of complement pathway components C3, Bb and sC5b-9 at times >9 months and up to 36 months in CLNP023B12001B.
•Determine plasma LNP023 concentration up to 12 months at trough
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•9-month visit
•6 to 9 months
•9-month visit
•9-month visit
• > 9 months
•3-month, 6-month, 9-month and 12-month visits
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 11 |
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 |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 6 |