| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Immunoglobulin A Nephropathy (IgAN) |
| Nefropatia da immunoglobuline A |
|
| E.1.1.1 | Medical condition in easily understood language |
An autoimmune disease resulting in inflammation of the kidney that can
lead to kidney failure in approximately one third of patients, over 10-20
years |
| Una patologia autoimmune che risulta in un'infiammazione del rene che può condurre ad insufficienza renale in circa un terzo dei pazienti, in 10-20 anni |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
| 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 |
|
| 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 |
The efficacy objective of the study is to determine the effect of sparsentan on proteinuria and renal function, as compared to an angiotensin receptor blocker, in patients with Immunoglobulin A Nephropathy (IgAN).
The safety objective of the study is to assess the safety and tolerability of sparsentan by double-blind monitoring of safety endpoints. |
L'obiettivo di efficacia è di determinare l’effetto di sparsentan sulla proteinuria e la funzione renale rispetto a un bloccante del recettore dell’angiotensina, in pazienti con nefropatia da immunoglobuline A (IgAN).
L'obiettivo di sicurezza è di valutare la sicurezza e la tollerabilità di sparsentan mediante monitoraggio in doppio cieco degli endpoint di sicurezza.
|
|
| E.2.2 | Secondary objectives of the trial |
| Not applicable |
| Non applicabile |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female, aged =18 years.
2. Biopsy-proven primary IgAN.
3. Urine total protein value =1.0 g/day at screening.
4. eGFR =30 mL/min/1.73 m2 at screening.
5. The patient has been on a stable dose of ACEI and/or ARB therapy for
at least 12 weeks prior to screening.
6. At screening, systolic blood pressure =150 mmHg and diastolic blood
pressure =100 mmHg.
7. The patient must agree to the use of two forms of contraception. |
1. Maschio o femmina con più di 18 anni.
2. Glomerulosclerosi focale segmentaria (GSFS) primaria confermata da biopsia o documentazione di una mutazione genetica
in una proteina dei podociti associata alla GSFS.
3. Soggetti ambosessi di età compresa tra 18 e 75 anni (Nota:
pazienti di età inferiore ai 18 anni potrebbero essere arruolati al di fuori del SEE).
4. Rapporto UP/C =1,5 g/g allo screening.
5. eGFR =30 ml/min/1,73 m2 allo screening.
6. Pressione sanguigna media da seduti =100/60 mmHg e =160/100 mmHg.
7. Il paziente deve acconsentire all’utilizzo di due metodi di
contraccezione. |
|
| E.4 | Principal exclusion criteria |
1. IgAN secondary to another condition.
2. Cellular glomerular crescents present in >25% of glomeruli on renal
biopsy within 6 months prior to screening.
3. History of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (hemoglobin A1c [HbA1c] >8%), or nonfasting blood glucose
>180 mg/dL at screening.
4. Any organ transplantation, with the exception of corneal transplants.
5. Treatment with any of the prohibited concomitant medications.
6. Treatment with any systemic immunosuppressive medications
(including corticosteroids) for >2 weeks within 3 months prior to
screening.
7. Documented history of heart failure and/or previous hospitalization
for heart failure or unexplained dyspnea, orthopnea, paroxysmal
nocturnal dyspnea, ascites, and/or peripheral edema.
8. Clinically significant cerebrovascular disease and/or coronary artery
disease.
9. Jaundice, hepatitis, or known hepatobiliary disease (including
asymptomatic cholelithiasis), or transaminase levels >2 times the upper
limit of the normal range at screening.
10. History of malignancy other than adequately treated basal cell or
squamous cell skin cancer or cervical carcinoma within the past 2 years.
11. A screening hematocrit value <27% or hemoglobin value <9 g/dL.
12. A screening potassium value of >5.5 mEq/L.
13. Female patient is pregnant, breastfeeding or planning to conceive
during the study.
14. Male patient plans to father a child during the course of the study.
15. Participation in a study of another investigational product within 28
days prior to screening. |
1. GSFS secondaria a un’altra condizione.
2.Il paziente presenta aree glomerulari cellulari a mezzaluna presenti in >25% dei glomeruli alla biopsia renale entro 6 mesi prima dello screening.
3.Anamnesi di diabete mellito di tipo 1, diabete mellito di tipo 2 non controllato (emoglobina A1c [HbA1c] >8%) o glicemia non a digiuno >180 mg/dl allo screening.
4.Il paziente è stato sottoposto a un qualsiasi trapianto d’organo, esclusi trapianti di cornea.
5.Il paziente ha bisogno di uno qualsiasi dei farmaci concomitanti proibiti
6.Il paziente ha assunto eventuali farmaci immunosoppressivi sistemici (inclusi i corticosteroidi) per >2 settimane nei 3 mesi precedenti lo screening.
7.Il paziente presenta un’anamnesi documentata di insufficienza cardiaca e/o precedente ricovero per insufficienza cardiaca o dispnea inspiegabile, ortopnea, dispnea parossistica notturna, ascite e/o edema periferico.
8.Il paziente presenta una malattia cerebrovascolare clinicamente significativa e/o arteriopatia coronarica
9.Il paziente presenta ittero, epatite o malattia epatobiliare nota (compresa la colelitiasi asintomatica), o livelli di alanina aminotransferasi (ALT) e/o aspartato aminotransferasi (AST) >2 volte il limite superiore dell’intervallo di normalità allo screening.
10.Il paziente presenta un’anamnesi di tumore maligno diverso da carcinoma cutaneo basocellulare o squamocellulare o carcinoma della cervice adeguatamente trattato nei 2 anni precedenti.
11.Il paziente presenta un valore di ematocrito allo screening <27% o di emoglobina <9 g/dl.
12.Il paziente presenta un valore di potassio allo screening >5,5 mEq/l.
13.Il paziente di sesso femminile è in stato di gravidanza o prevede di avviare una gravidanza nel corso dello studio, oppure sta allattando al seno.
16.Il paziente ha in programma di procreare nel corso dello studio.
17.Il paziente ha partecipato a uno studio di un altro prodotto sperimentale nei 28 giorni precedenti lo screening |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy Endpoints:
The primary efficacy endpoint is the change from baseline in the urine
protein/creatinine ratio (UP/C) at Week 36.
Safety Endpoints:
• Descriptive statistics will be used to summarize the safety data. |
Endpoint di efficacia:
L’endpoint primario di efficacia è la pendenza dell’eGFR.
Endpoint di sicurezza:
• Le statistiche descrittive saranno utilizzate per sintetizzare i dati di sicurezza |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Primary efficacy endpoints will be evaluated at Week 36. The primary safety endpoint will be evaluated from randomization to Week 114. |
| Gli endpoint primari di efficacia saranno valutati alla settimana 36. L'endpoint primario di sicurezza sarà valutato dalla randomizzazione alla settimana 114. |
|
| E.5.2 | Secondary end point(s) |
| Rate of change of eGFR |
Gli endpoint secondari di efficacia comprendono:
• Percentuale di pazienti che ottengono una riduzione target della proteinuria |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| From baseline to week 114 |
| Dal baseline alla Settimana 114 |
|
| 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 | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 83 |
| 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 | Information not present in EudraCT |
| 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 |
| Australia |
| Hong Kong |
| Korea, Republic of |
| New Zealand |
| Taiwan |
| United States |
| Belgium |
| Croatia |
| Czechia |
| Estonia |
| France |
| Germany |
| Italy |
| Lithuania |
| Poland |
| Portugal |
| Spain |
| United Kingdom |
|
| 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
|
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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