E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sickle Cell Disease; Sickle Cell Nephropathy |
Enfermedad de células falciformes; nefropatía de células falciformes |
|
E.1.1.1 | Medical condition in easily understood language |
Sickle Cell Disease; Sickle Cell Nephropathy |
Enfermedad de células falciformes; nefropatía de células falciformes |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040644 |
E.1.2 | Term | Sickle cell disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002077 |
E.1.2 | Term | Anaemia sickle cell |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 |
To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on albuminuria (ACR) decrease at 12 months |
El objetivo principal de este estudio es evaluar el efecto de crizanlizumab y el tratamiento estándar en comparación con el efecto único del tratamiento estándar en la disminución de albuminuria (CAC) a los 12 meses |
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E.2.2 | Secondary objectives of the trial |
- Evaluate the effect of crizanlizumab (SEG101) + standard of care (SOC) compared to SOC alone on change in albuminuria (ACR) - Evaluate the effect of SEG101 + SOC compared to SOC alone on albuminuria (ACR) decrease at 6 m - Evaluate the effect of SEG101 + SOC compared to SOC alone on protein to creatinine ratio (PCR) at 12 m - Evaluate the effect of SEG101 + SOC compared to SOC alone on the percentage change in eGFR - Evaluate the effect of SEG101 + SOC compared to SOC alone on ACR decline rate - Evaluate the effect of SEG101 + SOC compared to SOC alone on eGFR decline rate - Evaluate the effect of SEG101 + SOC compared to SOC alone on the progression of CKD at 12m - Evaluate overall safety and, tolerability of SEG101 + SOC compared to SOC alone - Assess the immunogenicity of SEG101 over the study period (treatment of 1y + 105d follow-up) - Evaluate healthcare resource utilization (visits to emergency room [ER] and hospitalizations) in SEG101 + SOC arm compared to SOC alone |
-Evaluar el efecto de crizanlizumab (SEG101) + tratamiento estándar (SOC) en comparación con el efecto único del tratamiento estándar en la disminución de albuminuria (CAC) - Evaluar el efecto de SEG101 + SOC en comparación con el efecto único del tratamiento estándar sobre la disminución de la albuminuria (CAC) a los 6 meses - Evaluar el efecto de SEG101 + SOC en comparación con el efecto único del tratamiento estándar sobre cociente proteína- creatinina (CPC) a los 12 meses - Evaluar el efecto de SEG101 + SOC en el efecto único del tratamiento estándar sobre el cambio porcentual en la TFGe - Evaluar el efecto de SEG101 + SOC en comparación con el efecto único del tratamiento estándar sobre la tasa de disminución del CAC, - Evaluar el efecto de SEG101 + SOC en comparación con el efecto único del tratamiento estándar sobre la tasa de disminución de la TFGe - Para el resto de objetivos véase el resumen del protocolo. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
o Confirmed diagnosis of SCD (HbSS and HbSβ0-thal SCD genotypes are eligible) o Patients with eGFR ≥ 45 to ≤ 120 mL/min/1.73 m2 based on CKD EPI formula o Patients with ACR of ≥ 100 to < 2000 mg/g o Receiving standard of care drug(s) for SCD for at least 6 months prior to study entry o Written informed consent (or assent/ parental consent for minor subjects) prior to any screening procedures
Additional inclusion criteria as per full protocol may apply |
- o Diagnóstico de ECF (Los genotipos de ECF de HbSS y HbSβ0-tal son elegibles). -o Pacientes con TFGe entre >=45 y <=120 ml/min/1,73 m2 basándose en la fórmula desarrollada por el grupo Chronic Kidney Disease Epidemiology Collaboration. -o Pacientes con un CAC entre >=100 y <2000 mg/g. -o Pacientes que reciban fármacos estándares para la ECF o ERC. durante al menos 6 meses antes de su entrada en el estudio - o Firma del consentimiento informado (o consentimiento / consentimiento de los padres para pacientes menores de edad) antes de cualquier procedimiento de selección |
|
E.4 | Principal exclusion criteria |
o History of stem cell transplant - Patients with evidence of AKI within 3 months of study entry o Blood pressure > 140/90 mmHg despite treatment o Patients undergoing hemodialysis o Received blood products within 30 days of Week 1 Day 1 o Participating in a chronic transfusion program o History of kidney transplant o Patients with hypoalbuminemia
Additional protocol-defined exclusion criteria may apply |
o Antecedentes de trasplante de células madre, Pacientes con evidencia de LRA durante los 3 meses anteriores a su entrada en el estudio. - o Presión arterial >140/90 mmHg a pesar del tratamiento. - o Pacientes sometidos a hemodiálisis. - o Haber recibido hemoderivados durante los 30 días anteriores al día 1 de la semana 1. - o Participación en un programa de transfusión crónico -o Antecedentes de trasplante de riñón. - o.Pacientes con hipoalbuminemia. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with ≥ 30% decrease in ACR at 12 months compared to baseline |
La variable principal, la proporción de pacientes con una disminución del CAC ≥30 % a los 12 meses respecto a la basal |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Baseline and Week 53 Day 1 |
Visita Basal y semana 53 Día 1 |
|
E.5.2 | Secondary end point(s) |
1. Mean change in ACR 2. Proportion of patients with ≥ 30% decrease in ACR 3. Proportion of patients with ≥ 20% improvement of PCR 4. Proportion of patients with a stable (within ± 20% change) PCR 5. Percentage change in eGFR 6. Slope of ACR decline based on ACR values 7. Slope of eGFR decline based on eGFR values 8. Proportion of patients with progression of CKD 9. Safety will be assessed by the frequency and severity of adverse events (AEs), deaths, SAEs, and laboratory abnormalities 10. Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab 11. PK parameters will accompany immunogenicity measurements to evaluate the impact of immunogenicity on exposure (PK) 12. Annualized rate of visits to ER and hospitalizations due to AKI events, VOCs, or other SCD complications |
1. Cambio medio en (CAC) 2. Proporción de pacientes con >=30% de disminución en (CAC) 3. Proporción de pacientes con >=20% de mejora de (CPC) 4. Proporción de pacientes con una (CPC) estable (dentro de ± 20% de cambio) 5. Porcentaje de cambio en TFGe 6. Pendiente de disminución de (CAC) basada en los valores de (CAC) 7. Pendiente de disminución de TFGe basada en valores de TFGe 8. Proporción de pacientes con progresión de TFGe 9. La seguridad será evaluada por la frecuencia y severidad de los acontecimientos adversos (AA), muertes, AA graves y anomalías de laboratorio. 10. Inmunogenicidad: medición de anticuerpos antidrogas (ADA) para crizanlizumab 11. Los parámetros PK acompañarán las mediciones de inmunogenicidad para evaluar el impacto de la inmunogenicidad en la exposición (PK) 12. Tasa anualizada de visitas a urgencias y hospitalizaciones debido a eventos de URG, COV u otras complicaciones de ECF |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline, Week 15 Day 1, Week 27 Day 1, Week 39 Day 1, Week 53 Day 1 2. Baseline, Week 27 Day 1 3. Baseline and Week 53 Day 1 4. Baseline and Week 53 Day 1 5. Baseline, Week 15 Day 1, Week 27 Day 1, Week 39 Day 1, Week 53 Day 1 6. Baseline, Week 15 Day 1, Week 27 Day 1, Week 39 Day 1, Week 53 Day 1 7. Baseline, Week 15 Day 1, Week 27 Day 1, Week 39 Day 1, Week 53 Day 1 8. Baseline and Week 53 Day 1 9. all timepoints 10. Week 1 Day 1, Week 3 Day 1, Week 11 Day 1, Week 23 Day 1, Week 39 Day 1, Week 53 Day 1, 105 Day follow-up 11. Week 1 Day 1, Week 3 Day 1, Week 11 Day 1, Week 23 Day 1, Week 39 Day 1, Week 53 Day 1, 105 Day follow-up 12. all timepoints |
1. Visita Basal, Semana 15 Día 1, Semana 27 Día 1, Semana 39 Día 1, Semana 53 Día 1 2. Visita Basal, Semana 27 Día 1 3. Visita Basal y semana 53 Día 1 4. Visita Basal y semana 53 Día 1 5. Visita Basal, Semana 15 Día 1, Semana 27 Día 1, Semana 39 Día 1, Semana 53 Día 1 6. Visita Basal, Semana 15 Día 1, Semana 27 Día 1, Semana 39 Día 1, Semana 53 Día 1 7. Visita Basal, Semana 15 Día 1, Semana 27 Día 1, Semana 39 Día 1, Semana 53 Día 1 8. Visita Basal y semana 53 Día 1 9. Todas las fechas 10. Semana 1 Día 1, Semana 3 Día 1, Semana 11 Día 1, Semana 23 Día 1, Semana 39 Día 1, Semana 53 Día 1, 105 Días de seguimiento 11. Semana 1 Día 1, Semana 3 Día 1, Semana 11 Día 1, Semana 23 Día 1, Semana 39 Día 1, Semana 53 Día 1, 105 Días de seguimiento 12. Todas las fechas. |
|
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 | No |
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 |
healthcare resource utilization, immunogenicity |
Utilización de recursos sanitarios, inmunogenicidad |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Brazil |
Egypt |
France |
Ghana |
Greece |
India |
Italy |
Kenya |
Lebanon |
Netherlands |
Panama |
South Africa |
Spain |
Turkey |
United Kingdom |
United States |
|
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
|
LVLS |
LVLS Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 28 |