E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sickle Cell Disease; Sickle Cell Nephropathy |
|
E.1.1.1 | Medical condition in easily understood language |
Sickle Cell Disease; Sickle Cell Nephropathy |
|
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 |
|
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 descriptively the effect of crizanlizumab + standard of care and standard of care alone on albuminuria (ACR) decrease at 12 months |
|
E.2.2 | Secondary objectives of the trial |
- Evaluate descriptively the effect of crizanlizumab (SEG101)+standard of care (SOC)&SOC alone on change in albuminuria (ACR)
- Evaluate descriptively the effect of SEG101+SOC&SOC alone on albuminuria (ACR) decrease at 6 m
- Evaluate descriptively the effect of SEG101+SOC&SOC alone on protein to creatinine ratio (PCR) at 12 m
- Evaluate descriptively the effect of SEG101+SOC&SOC alone on the percentage change in eGFR
- Evaluate descriptively the effect of SEG101+SOC&SOC alone on ACR decline rate
- Evaluate descriptively the effect of SEG101+SOC&SOC alone on eGFR decline rate
- Evaluate descriptively the effect of SEG101+SOC&SOC alone on the progression of CKD at 12m
- Evaluate overall safety and, tolerability of SEG101+SOC&SOC alone
- Assess the immunogenicity of SEG101 over the study period (treatment of 1y + 105d follow-up)
- Evaluate descriptively healthcare resource utilization (visits to emergency room [ER] and hospitalizations) in SEG101+SOC arm&SOC alone |
|
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 ≤ 140 mL/min/1.73 m2 based on CKD EPI
formula (patients ≥ 18) or the Creatinine-based "Bedside Schwartz"
equation (patients < 18)
o Patients with ACR of ≥ 100 to < 2000 mg/g (taken as an average of
the three screening ACR values to determine eligibility)
o Receiving at least 1 standard of care drug(s) for SCD related CKD
according to local guidelines. if receiving HU/HC, the patient must have
been receiving HU/HC for at least 6 months and on a stable dose for 3
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. |
|
E.4 | Principal exclusion criteria |
o History of stem cell transplant
o Patients with evidence of AKI within 3 months of study entry (can
decrease interval to within 6 weeks of study entry only if renal function
has returned to pre-AKI values prior to study entry)
o Blood pressure > 140/90 mmHg despite treatment
o Body mass index of ≥ 35
o Patients undergoing renal replacement therapy (ie. hemodialysis,
peritoneal dialysis,
hemofiltration and kidney transplantation)
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 defined as <25 g/L
Additional protocol-defined exclusion criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with ≥ 30% decrease in ACR at 12 months from baseline |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Baseline and Week 53 Day 1 |
|
E.5.2 | Secondary end point(s) |
1. Mean change in ACR
2. Proportion of patients with ≥ 30% decrease in ACR at 6 months from baseline
3. Proportion of patients with PCR improvement and stable PCR (improvement: ≥ 20% decrease in PCR from baseline; stable: within ±20% change from baseline) at 12 months from baseline
4. Percentage change in eGFR
5. Slope of ACR decline based on ACR values
6. Slope of eGFR decline based on eGFR values
7. Proportion of patients with progression of CKD
8. Safety will be assessed by the frequency and severity of adverse events (AEs), deaths, measurement of vital signs, ECG assessments, SAEs, and laboratory abnormalities
9. Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab
10.Crizanlizumab PK measurements will accompany immunogenicity measurements
11. Annualized rate of visits to ER and hospitalizations due to AKI events, VOCs, or other SCD complications |
|
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
|
|
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 |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 |
Ghana |
India |
Kenya |
Lebanon |
Panama |
South Africa |
Turkey |
United States |
France |
Greece |
Italy |
United Kingdom |
Netherlands |
Spain |
|
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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 21 |