Sickle Cell Disease (SCD)
Conditions
Keywords
SEG101, Sickle Cell Disease, SCD, Crizanlizumab, Sickle cell nephropathy, chronic kidney disease, CKD, albuminuria (ACR), renal function, standard of care
Brief summary
The goal of the study was to evaluate descriptively the effect of crizanlizumab + standard of care and standard of care alone on renal function in sickle cell disease patients ≥ 16 years with chronic kidney disease due to sickle cell nephropathy.
Detailed description
Approximately 50 patients were to be randomized 1:1 to receive either crizanlizumab (5 mg/kg) + standard of care or standard of care alone. Patients were stratified at randomization based on chronic kidney disease (CKD) risk category (moderate risk or high/very high risk) and hydroxyurea/hydroxycarbamide (HU/HC) prescription (Yes/No). The CKD risk categories used for stratification were based on both Estimated glomerular filtration rate(eGFR) and albuminuria assessed by Albumin/creatinine ratio (ACR).
Interventions
DRUGCrizanlizuamb
Crizanlizumab is a concentrate for solution for infusion, i.v. use. Supplied in single use 10 mL vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab
DRUGStandard of Care
HU/HC (hydroxyurea/hydroxycarbamide) and/or ACE (angiotensin-converting enzyme) inhibitors and/or ARBs (angiotensin-receptor blocker)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of SCD (HbSS and HbSβ0-thal SCD genotypes are eligible) * 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) * Patients with ACR of ≥ 100 to \< 2000 mg/g (taken as an average of the three screening ACR values to determine eligibility) * Receiving at least 1 standard of care drug(s) for SCD-related CKD: 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, and/or an ACE inhibitor and/or ARB for 3 months and on a stable dose for those 3 months. * Hb ≥ 4.0 g/dL, absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L, and platelet count ≥ 75 x 10\^9/L * Adequate hepatic function as defined by: * Alanine aminotransferase (ALT) \< 3.0 x upper limit of normal (ULN) * Direct (conjugated) bilirubin ≤ 3.0 x ULN * Written informed consent (or assent/ parental consent for minor subjects) prior to any screening procedures
Exclusion criteria
* History of stem cell transplant * 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) * Blood pressure \> 140/90 mmHg despite treatment * Patients undergoing renal replacement therapy (ie. hemodialysis, peritoneal dialysis, hemofiltration and kidney transplantation) * Received blood products within 30 days of Week 1 Day 1 * Participating in a chronic transfusion program * History of kidney transplant * Patients with hypoalbuminemia * Body mass index of ≥ 35 * Currently receiving or received voxelotor within 6 months of screening * Patient has received crizanlizumab and/or other selectin inhibitor or plans to receive it during the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 12 Months | Baseline to 12 months | The effect of SEG101 on clinical disease activity was measured by at least 30% decrease in Albumin to Creatinine Ratio (ACR) from baseline to month 12. A reduction from baseline indicates improvement in patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 6 Months | Baseline to 6 months | The effect of SEG101 on clinical disease activity was measured by at least 30% decrease in Albumin to Creatinine Ratio (ACR) from baseline to month 6. A reduction from baseline indicates improvement in patients. |
| Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months | Baseline to 12 months | The effect of SEG101 on clinical disease activity was measured by counting patients who had Stable PCR: within ± 20% change from baseline to month 12. PCR improvement: ≥ 20% decrease in PCR from baseline indicates improvement in patients. |
| Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Baseline to 3, 6, 9, and 12 months | The percentage change in eGFR was calculated as the post-baseline eGFR value minus the baseline eGFR divided by the eGFR at baseline. A reduction from baseline indicates improvement in participants. |
| Slope of Albumin to Creatinine Ratio (ACR) Decline | Baseline to 12 months | The effect of SEG101 on clinical disease activity was measured by the slope of ACR decline between baseline and Month 12. A reduction from baseline indicates improvement in patients. |
| Slope of Estimated Glomerular Filtration Rate (eGFR) Decline | Baseline to 12 months | The effect of SEG101 on clinical disease activity was measured by the slope of eGFR between baseline and Month 12. The calculation of eGFR is based on the chronic kidney disease epidemiology collaboration (CKD-EPI) (for patients ≥ 18) and Creatinine-based Bedside Schwartz (for patients \< 18) equations. A reduction in drop rate from baseline indicates improvement in patients. |
| Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Baseline to 3, 6, 9, and 12 months | The effect of SEG101 on clinical disease activity was measured by the change in albuminuria (ACR) between baseline and month 3, baseline and month 6, baseline and month 9, baseline and month 12. A reduction from baseline indicates improvement in patients. |
| Shift Table for Chronic Kidney Disease (CKD) Progression | Baseline and month 12 | The effect of SEG101 on clinical disease activity was measured by percentage of participants with CKD progression between baseline and Month 12. A reduction from baseline indicates improvement in patients. |
| Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab | Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months | The effect of SEG101 on clinical disease activity was measured by percentage of participants shifted to different worst post-baseline categories between baseline and Month 12. An increase in percentage shifting from higher category to lower category indicates improvement in patients. Baseline is defined as the last non-missing value prior to the first dose. |
| Annualized Rate of Visits to Emergency Room (ER) and Hospitalizations | Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months | The effect of SEG101 on clinical disease activity was measured by summarizing the annualized rate of visits to ER and hospitalizations between baseline and 1 year 4 months. Annualized rate of hospitalizations and ER visits due to VOC =(Number of ER or hospitalizations reported until End date x 365.25)/(End date-date of first dose of study treatment+1). A reduction from baseline indicates improvement in patients. |
| Mean Serum Concentration (Ctrough) of Crizanlizumab | Pre-dose and 336 hours post-dose on Week 3 Day 1; pre-dose and 672 hours post dose on Week 11 Day 1, Week 23 Day 1 and Week 39 Day 1; and 672 hours post dose on Week 53 Day 1 | The effect of SEG101 on clinical disease activity was measured by checking the concentration of the Drug in serum at different time points. Crizanlizumab pre-dose/trough pharmacokinetic samples were taken at select time points. |
| Percentage of Participants With Progression of Chronic Kidney Disease (CKD) at 12 Months | Baseline to 12 months | The effect of SEG101 on clinical disease activity was measured by percentage of participants with CKD progression between baseline and Month 12. A reduction from baseline indicates improvement in participants. CKD progression is defined as an increase in CKD progression category, a 25% or greater drop in eGFR from baseline or at least 50% increase in ACR for patients with severe (A3) albuminuria and a doubling of albumin levels in patients with moderate (A2) albuminuria. |
Countries
Brazil, France, Greece, Ireland, Lebanon, Netherlands, Panama, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Patients were enrolled in 24 centers in 11 countries.
Pre-assignment details
Patients were stratified at randomization based on CKD risk category (moderate risk or high/very high risk) and HU/HC use (Yes/No). At visit Week 1 Day 1 all eligible patients were randomized via Interactive Response Technology (IRT) to one of the treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Crizanlizumab + Standard of Care 5 mg/kg by intravenous (i.v.) infusion at Week 1 Day 1, Week 3 Day 1 and Day 1 of every 4-week cycle until Week 51 in addition to their usual standard of care treatment. | 30 |
| Standard of Care (SOC) Patients in the standard of care alone arm will continue to receive their usual standard of care treatment. | 28 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 2 |
Baseline characteristics
| Characteristic | Crizanlizumab + Standard of Care | Standard of Care (SOC) | Total |
|---|---|---|---|
| Age, Continuous | 41.8 Years STANDARD_DEVIATION 9.52 | 41.1 Years STANDARD_DEVIATION 8.71 | 41.5 Years STANDARD_DEVIATION 9.06 |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 15 Participants | 30 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 12 Participants | 27 Participants |
| Sex: Female, Male Female | 20 Participants | 17 Participants | 37 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 28 | 0 / 57 |
| other Total, other adverse events | 21 / 29 | 19 / 28 | 40 / 57 |
| serious Total, serious adverse events | 2 / 29 | 2 / 28 | 4 / 57 |
Outcome results
Primary
Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 12 Months
The effect of SEG101 on clinical disease activity was measured by at least 30% decrease in Albumin to Creatinine Ratio (ACR) from baseline to month 12. A reduction from baseline indicates improvement in patients.
Time frame: Baseline to 12 months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crizanlizumab + Standard of Care | Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 12 Months | 33.3 Percentage of participants |
| Standard of Care (SOC) | Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 12 Months | 21.4 Percentage of participants |
95% CI: [0.53, 7.14]
Secondary
Annualized Rate of Visits to Emergency Room (ER) and Hospitalizations
The effect of SEG101 on clinical disease activity was measured by summarizing the annualized rate of visits to ER and hospitalizations between baseline and 1 year 4 months. Annualized rate of hospitalizations and ER visits due to VOC =(Number of ER or hospitalizations reported until End date x 365.25)/(End date-date of first dose of study treatment+1). A reduction from baseline indicates improvement in patients.
Time frame: Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crizanlizumab + Standard of Care | Annualized Rate of Visits to Emergency Room (ER) and Hospitalizations | 0.6 ER or hospitalizations/year | Standard Deviation 2.1 |
| Standard of Care (SOC) | Annualized Rate of Visits to Emergency Room (ER) and Hospitalizations | 1.1 ER or hospitalizations/year | Standard Deviation 3 |
Secondary
Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months
The effect of SEG101 on clinical disease activity was measured by the change in albuminuria (ACR) between baseline and month 3, baseline and month 6, baseline and month 9, baseline and month 12. A reduction from baseline indicates improvement in patients.
Time frame: Baseline to 3, 6, 9, and 12 months
Population: Participants in the FAS with an available assessment for the outcome measure at baseline and at each timepoint. The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Crizanlizumab + Standard of Care | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Month 12 change from BL | 17.7 mg/g | Standard Deviation 620.7 |
| Crizanlizumab + Standard of Care | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Baseline (BL) | 597.0 mg/g | Standard Deviation 534.3 |
| Crizanlizumab + Standard of Care | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Month 3 change from BL | -56.9 mg/g | Standard Deviation 362.8 |
| Crizanlizumab + Standard of Care | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Month 6 change from BL | -98.5 mg/g | Standard Deviation 382.2 |
| Crizanlizumab + Standard of Care | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Month 9 change from BL | -12.3 mg/g | Standard Deviation 586.6 |
| Standard of Care (SOC) | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Month 9 change from BL | 95.2 mg/g | Standard Deviation 376.2 |
| Standard of Care (SOC) | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Month 6 change from BL | -35.4 mg/g | Standard Deviation 384.4 |
| Standard of Care (SOC) | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Baseline (BL) | 499.0 mg/g | Standard Deviation 486.7 |
| Standard of Care (SOC) | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Month 12 change from BL | 14.7 mg/g | Standard Deviation 307.1 |
| Standard of Care (SOC) | Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months | Month 3 change from BL | 159.0 mg/g | Standard Deviation 809.9 |
Secondary
Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab
The effect of SEG101 on clinical disease activity was measured by percentage of participants shifted to different worst post-baseline categories between baseline and Month 12. An increase in percentage shifting from higher category to lower category indicates improvement in patients. Baseline is defined as the last non-missing value prior to the first dose.
Time frame: Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
Population: Participants in the FAS with an available assessment for the outcome measure at baseline and up to 12 months. The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Crizanlizumab + Standard of Care | Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab | Negative at baseline to Only last sample positive | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab | Negative at baseline to Any positive | 3.4 Percentage of participants |
| Crizanlizumab + Standard of Care | Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab | Negative at baseline to All positive | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab | Negative at baseline to All Negative | 89.7 Percentage of participants |
| Crizanlizumab + Standard of Care | Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab | Negative at baseline to All Missing | 6.9 Percentage of participants |
Secondary
Mean Serum Concentration (Ctrough) of Crizanlizumab
The effect of SEG101 on clinical disease activity was measured by checking the concentration of the Drug in serum at different time points. Crizanlizumab pre-dose/trough pharmacokinetic samples were taken at select time points.
Time frame: Pre-dose and 336 hours post-dose on Week 3 Day 1; pre-dose and 672 hours post dose on Week 11 Day 1, Week 23 Day 1 and Week 39 Day 1; and 672 hours post dose on Week 53 Day 1
Population: Participants in the FAS with an available assessment for the outcome measure at baseline and up to 12 months. The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 3 Day1: 0 hours pre-dose | 11.6 μg/mL | Standard Deviation 2.66 |
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 3 Day1: 336 hours post-dose | 12.1 μg/mL | Standard Deviation 2.38 |
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 11 Day1: 0 hours pre-dose | 4.78 μg/mL | Standard Deviation 3.49 |
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 11 Day1: 672 hours post-dose | 5.67 μg/mL | Standard Deviation 3.11 |
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 23 Day1: 0 hours pre-dose | 4.77 μg/mL | Standard Deviation 2.82 |
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 23 Day1: 672 hours post-dose | 5.54 μg/mL | Standard Deviation 2.21 |
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 39 Day1: 0 hours pre-dose | 5.55 μg/mL | Standard Deviation 2.34 |
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 39 Day1: 672 hours post-dose | 5.16 μg/mL | Standard Deviation 2.1 |
| Crizanlizumab + Standard of Care | Mean Serum Concentration (Ctrough) of Crizanlizumab | Week 53 Day1: 672 hours post-dose | 15.2 μg/mL | Standard Deviation 5.18 |
Secondary
Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
The percentage change in eGFR was calculated as the post-baseline eGFR value minus the baseline eGFR divided by the eGFR at baseline. A reduction from baseline indicates improvement in participants.
Time frame: Baseline to 3, 6, 9, and 12 months
Population: Participants in the FAS with an available assessment for the outcome measure at baseline and at each timepoint. The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Crizanlizumab + Standard of Care | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Month 3 change from BL | -2.5 Percentage change in eGFR | Standard Deviation 8.9 |
| Crizanlizumab + Standard of Care | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Month 6 change from BL | -2.7 Percentage change in eGFR | Standard Deviation 5.5 |
| Crizanlizumab + Standard of Care | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Month 9 change from BL | -0.2 Percentage change in eGFR | Standard Deviation 12.8 |
| Crizanlizumab + Standard of Care | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Month 12 change from BL | -4.9 Percentage change in eGFR | Standard Deviation 14.1 |
| Standard of Care (SOC) | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Month 12 change from BL | -6.3 Percentage change in eGFR | Standard Deviation 13.2 |
| Standard of Care (SOC) | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Month 3 change from BL | -0.5 Percentage change in eGFR | Standard Deviation 10 |
| Standard of Care (SOC) | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Month 9 change from BL | -2.7 Percentage change in eGFR | Standard Deviation 8.7 |
| Standard of Care (SOC) | Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Month 6 change from BL | -7.3 Percentage change in eGFR | Standard Deviation 12.7 |
Comparison: From baseline to 3 months95% CI: [-5.53, 4.65]
Comparison: From baseline to 6 months95% CI: [-2.02, 11.4]
Comparison: From baseline to 9 months95% CI: [-3.58, 11.68]
Comparison: From baseline to 12 months95% CI: [-3.28, 13.67]
Secondary
Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 6 Months
The effect of SEG101 on clinical disease activity was measured by at least 30% decrease in Albumin to Creatinine Ratio (ACR) from baseline to month 6. A reduction from baseline indicates improvement in patients.
Time frame: Baseline to 6 months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crizanlizumab + Standard of Care | Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 6 Months | 30.0 Percentage of participants |
| Standard of Care (SOC) | Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 6 Months | 35.7 Percentage of participants |
95% CI: [0.23, 2.31]
Secondary
Percentage of Participants With Progression of Chronic Kidney Disease (CKD) at 12 Months
The effect of SEG101 on clinical disease activity was measured by percentage of participants with CKD progression between baseline and Month 12. A reduction from baseline indicates improvement in participants. CKD progression is defined as an increase in CKD progression category, a 25% or greater drop in eGFR from baseline or at least 50% increase in ACR for patients with severe (A3) albuminuria and a doubling of albumin levels in patients with moderate (A2) albuminuria.
Time frame: Baseline to 12 months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crizanlizumab + Standard of Care | Percentage of Participants With Progression of Chronic Kidney Disease (CKD) at 12 Months | 13.3 Percentage of participants |
| Standard of Care (SOC) | Percentage of Participants With Progression of Chronic Kidney Disease (CKD) at 12 Months | 32.1 Percentage of participants |
95% CI: [0.09, 1.21]
Secondary
Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months
The effect of SEG101 on clinical disease activity was measured by counting patients who had Stable PCR: within ± 20% change from baseline to month 12. PCR improvement: ≥ 20% decrease in PCR from baseline indicates improvement in patients.
Time frame: Baseline to 12 months
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Crizanlizumab + Standard of Care | Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months | Percentage of participants with PCR improvement at 12 months | 33.3 Percentage of participants |
| Crizanlizumab + Standard of Care | Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months | Percentage of participants with stable PCR at 12 months | 16.7 Percentage of participants |
| Standard of Care (SOC) | Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months | Percentage of participants with PCR improvement at 12 months | 35.7 Percentage of participants |
| Standard of Care (SOC) | Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months | Percentage of participants with stable PCR at 12 months | 25.0 Percentage of participants |
Comparison: PCR Improvement95% CI: [0.29, 3.02]
Comparison: Stable PCR95% CI: [0.18, 3.2]
Secondary
Shift Table for Chronic Kidney Disease (CKD) Progression
The effect of SEG101 on clinical disease activity was measured by percentage of participants with CKD progression between baseline and Month 12. A reduction from baseline indicates improvement in patients.
Time frame: Baseline and month 12
Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline | 43.3 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 4 at Worst post-baseline | 50.0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 2 at Worst post-baseline | 15.4 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 3 at Worst post-baseline | 50.0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 3 at Worst post-baseline | 69.2 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing at baseline | 10.0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 4 at Worst post-baseline | 7.7 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline | 6.7 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Missing at Worst post-baseline | 7.7 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 2 at Worst post-baseline | 100.0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline | 36.7 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline | 3.3 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 2 at Worst post-baseline | 36.4 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 3 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 3 at Worst post-baseline | 45.5 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 3 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Missing at Worst post-baseline | 100.0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline | 0 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Missing at Worst post-baseline | 18.2 Percentage of participants |
| Crizanlizumab + Standard of Care | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 3 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline | 14.3 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 2 at Worst post-baseline | 75.0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 3 at Worst post-baseline | 25.0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline | 53.6 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 2 at Worst post-baseline | 40.0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 3 at Worst post-baseline | 53.3 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 4 at Worst post-baseline | 6.7 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline | 28.6 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 2 at Worst post-baseline | 12.5 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 3 at Worst post-baseline | 75.5 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 4 at Worst post-baseline | 12.5 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline | 3.6 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 3 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 4 at Worst post-baseline | 100.0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 3 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing at baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 3 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| Standard of Care (SOC) | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 4 at Worst post-baseline | 3.8 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Missing at Worst post-baseline | 100.0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 3 at Worst post-baseline | 50.0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Cat 2 at Worst post-baseline | 38.5 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 3 at Worst post-baseline | 20.0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 3 at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline | 44.8 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline | 8.6 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing baseline to Cat 3 at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Missing at Worst post-baseline | 4.8 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 4 at Worst post-baseline | 9.5 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline to Missing at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline | 5.2 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 3 at Worst post-baseline | 71.4 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 4 at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 2 at Worst post-baseline | 0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline to Cat 2 at Worst post-baseline | 14.3 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 0 at baseline to Cat 2 at Worst post-baseline | 80.0 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 3 at Worst post-baseline | 33.3 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 2 at baseline | 36.2 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat Missing at baseline | 5.2 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 3 at baseline to Cat 4 at Worst post-baseline | 66.7 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 1 at baseline to Missing at Worst post-baseline | 7.7 Percentage of participants |
| All Patients | Shift Table for Chronic Kidney Disease (CKD) Progression | Cat 4 at baseline | 0 Percentage of participants |
Secondary
Slope of Albumin to Creatinine Ratio (ACR) Decline
The effect of SEG101 on clinical disease activity was measured by the slope of ACR decline between baseline and Month 12. A reduction from baseline indicates improvement in patients.
Time frame: Baseline to 12 months
Population: Participants in the FAS with an available assessment for the outcome measure at baseline and up to 12 months. The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Crizanlizumab + Standard of Care | Slope of Albumin to Creatinine Ratio (ACR) Decline | 1.70 mg/g per month | Standard Error 8.655 |
| Standard of Care (SOC) | Slope of Albumin to Creatinine Ratio (ACR) Decline | 4.49 mg/g per month | Standard Error 8.159 |
Secondary
Slope of Estimated Glomerular Filtration Rate (eGFR) Decline
The effect of SEG101 on clinical disease activity was measured by the slope of eGFR between baseline and Month 12. The calculation of eGFR is based on the chronic kidney disease epidemiology collaboration (CKD-EPI) (for patients ≥ 18) and Creatinine-based Bedside Schwartz (for patients \< 18) equations. A reduction in drop rate from baseline indicates improvement in patients.
Time frame: Baseline to 12 months
Population: Participants in the FAS with an available assessment for the outcome measure at baseline and up to 12 months. The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Crizanlizumab + Standard of Care | Slope of Estimated Glomerular Filtration Rate (eGFR) Decline | -0.1 mL/min/1.73 m^2 per month | Standard Error 0.18 |
| Standard of Care (SOC) | Slope of Estimated Glomerular Filtration Rate (eGFR) Decline | -0.4 mL/min/1.73 m^2 per month | Standard Error 0.16 |