Focal Segmental Glomerulosclerosis
Conditions
Keywords
FSGS, Glomerulosclerosis, Proteinuria
Brief summary
An Open Label, Intra-Subject Dose Escalation Study of CCX140 B in Subjects with Primary FSGS and Nephrotic Syndrome
Detailed description
An Open Label, Intra-Subject Dose Escalation Study of CCX140 B in Subjects with Primary Focal Segmental Glomerulosclerosis (FSGS) and Nephrotic Syndrome. The aim of this study is to explore the effect of CCX140-B, a selective antagonist of C-C chemokine receptor type 2, on proteinuria in subjects with FSGS. Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.
Interventions
DRUGCCX140-B
Orally administered tablet
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-Label, Intra-Subject, Dose Escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects aged 18 years and older 2. Primary FSGS based on renal biopsy findings consistent with FSGS and based on presentation of histopathology, medical history and clinical course OR subjects with genetic risk factors with presentations that are otherwise consistent with primary FSGS 3. Urinary total protein:creatinine ratio (UPCR) ≥ 3.5 g protein/g creatinine at screening
Exclusion criteria
1. Pregnant or nursing 2. History of organ transplantation, including renal transplantation 3. Currently on an organ transplant waiting list or there's a reasonable possibility of getting an organ transplant within 6 months of screening 4. Histological FSGS subtype of collapsing variant 5. Subjects who initiated, discontinued or changed dose of anti-CD20 monoclonal antibodies within 16 weeks (4 months) prior to screening are excluded. Subjects who initiated treatment with anti-CD20 monoclonal antibodies \>16 weeks (4 months) prior to screening are permitted if deemed safe by the investigator and only if they intend to remain on continued, unchanged therapy at a dosing interval that has been documented to achieve continuous B cell depletion for the given patient. 6. Subjects who discontinued Rituximab or other anti-CD20 monoclonal antibodies \>16 weeks (4 months) prior to screening without confirmed recovery of CD20+ B cell population to within normal range are excluded. Subjects who discontinued rituximab or other anti-CD20 monoclonal antibodies \>16 weeks (4 months) prior to screening with confirmed recovery of CD20+ B cell population to within normal range are permitted in the study. UPCR and other urine protein assessments up to 1 year prior to screening (if available) that were performed in these patients as part of the clinical routine should be recorded in the medical history. 7. Body Mass Index (BMI) ≥ 40
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Subjects With a Reduction in Urine Protein to Creatinine Ratio (UPCR) of at Least 20% | Baseline to week 12 | Number of subjects with a reduction in Urine Protein to Creatinine Ratio (UPCR) of at least 20% , i.e., ≥20%, by Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of Partial or Complete Remission of UPCR Through Week 12 and Through the End of Treatment | Baseline to week 12 | Partial and complete remission were defined as follows: Partial remission (included all of the following): * Reduction from baseline by ≥50% in urine protein:creatinine ratio (UPCR) * Reduction in UPCR to a level that was \<3.5 g/g * Subject could not have been a treatment failure Complete remission (included all of the following): * Reduction in UPCR to \<0.3 g/g * Serum albumin within normal range * For subjects with abnormal serum creatinine levels at baseline, return to normal levels * For subjects with normal serum creatinine levels at baseline, final value within 20% of baseline levels * Subject could not have been a treatment failure |
| Proportion of Subjects With Achievement of Complete Remission During the Treatment Period | Baseline to week 52 | Complete remission is defined as reduction in urine protein:creatinine ratio (UPCR) to \<0.3 g/g, normal serum albumin, and normal serum creatinine levels or within 20% of baseline levels. |
| Time Taken of Subjects to Achieve Complete Remission During the Treatment Period | Baseline to week 52 | Complete remission is defined as reduction in urine protein:creatinine ratio (UPCR) to \<0.3 g/g, normal serum albumin, and normal serum creatinine levels or within 20% of baseline levels. |
| Change From Baseline in Urine Protein:Creatinine Ratio (UPCR) Over Time | Baseline to week 12 and week 52 | Mean change from baseline in urinary protein:creatinine ratio (UPCR) over time. |
| Assessment of Time to and Proportion of Subjects With Achievement of Partial Remission During the Treatment Period | Baseline to week 52 | Partial remission is defined as reduction from baseline by ≥50% in UPCR, reduction in UPCR to a level that was \<3.5 g/g. |
| Time to Rescue Therapy | Baseline to week 52 | Based on Investigator or physician initiation of glucocorticoids or new immunosuppressive agents or new major treatment modalities (e.g. plasmapheresis, dialysis) |
| Mean Change From Baseline for eGFR CKD-EPI Creatinine-Cystatin C Equation Over Time | Baseline to Week 12 and Week 52 | CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate; |
| Mean Change From Baseline for the eGFR CKD-EPI Creatinine Equation Over Time | Baseline to Week 12 and Week 52 | CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate |
| Mean Change From Baseline for the MDRD Creatinine Equation Over Time | Baseline to Week 12 and Week 52 | MDRD = Modification of Diet in Renal Disease. The mean eGFR (using the MDRD Creatinine equation) change from baseline to Week 12 and Week 52 |
| Effect of CCX140-B Treatment on Quality of Life Endpoint SF-36V2 | Baseline to Week 52 | Summary of the Effect of CCX140-B Treatment on Quality of Life Endpoints SF-36V2 for the overall trial SF-36v2: Medical Outcomes Survey Short Form-36 version 2. SF-36v2 measures each of the following eight health domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Scores on each item are summed and averaged. The SF-36v2 component domain scores range from 0 (worst health) to 100 (best health). |
| Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the Overall Trial | Baseline to Week 12 and Week 52 | Summary of the Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the overall trial EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels. The EQ-5D-5L consists of : the EQ-5D descriptive system. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine. |
| Changes to Laboratory Parameters Related to Renal Function Including Serum Albumin, Creatinine, Cystatin C, Urinary Albumin:Creatinine Ratio, Total 24-hour Protein Excretion During the Trial | Baseline to Day 57 | Changes to laboratory parameters related to renal function including serum albumin, creatinine, cystatin C, urinary albumin:creatinine ratio, total 24-hour protein excretion during the trial |
| Mean Change From Baseline for eGFR Using the CKD-EPI Cystatin C Equation Over Time | Baseline to Week 12 and Week 52 | eGFR-Estimated Glomerular Filtration Rate;CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CCX140-B CCX140-B is an orally administered tablet All enrolled subjects will initially be treated with the active study medication CCX140-B at a dose of 5 mg twice daily. Dose will increase in a step-wise fashion up to 15 mg twice daily. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | CCX140-B |
|---|---|
| Age at diagnosis of FSGS (years) | 35.2 years STANDARD_DEVIATION 19.18 |
| Age, Continuous | 37.6 years STANDARD_DEVIATION 18.65 |
| All calcineurin inhibitors combined No | 3 Participants |
| All calcineurin inhibitors combined Yes | 2 Participants |
| Baseline eGFR (CKD-EPI Creatinine-Cystatin C) | 50.60 mL/min/1.73m² STANDARD_DEVIATION 23.923 |
| Baseline eGFR (MDRD Creatinine) | 54.40 mL/min/1.73m² STANDARD_DEVIATION 26.245 |
| Baseline UACR - 24-hour | 3.24 g protein/ g creatinine STANDARD_DEVIATION 1.316 |
| Baseline UACR - morning void | 4.12 g protein/ g creatinine STANDARD_DEVIATION 1.394 |
| Baseline UPCR - 24-hour | 4.80 g protein/ g creatinine STANDARD_DEVIATION 1.376 |
| Baseline UPCR - morning void | 5.71 g protein/ g creatinine STANDARD_DEVIATION 1.563 |
| Concomitant use of ACE inhibitor or ARB No | 0 Participants |
| Concomitant use of ACE inhibitor or ARB Yes | 5 Participants |
| Concomitant use of glucocorticoids and/or immunosuppressive medications No | 1 Participants |
| Concomitant use of glucocorticoids and/or immunosuppressive medications Yes | 4 Participants |
| Concomitant use of rituximab or other anti-CD20 No | 5 Participants |
| Concomitant use of rituximab or other anti-CD20 Yes | 0 Participants |
| Duration of FSGS (months) | 29.4 months STANDARD_DEVIATION 16.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Glomeruli showing segmental lesions ≤1 | 1 Participants |
| Glomeruli showing segmental lesions >1 | 4 Participants |
| Podocyte effacement <30% | 1 Participants |
| Podocyte effacement ≥30% | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment Poland | 1 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
The Number of Subjects With a Reduction in Urine Protein to Creatinine Ratio (UPCR) of at Least 20%
Number of subjects with a reduction in Urine Protein to Creatinine Ratio (UPCR) of at least 20% , i.e., ≥20%, by Week 12.
Time frame: Baseline to week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CCX140-B | The Number of Subjects With a Reduction in Urine Protein to Creatinine Ratio (UPCR) of at Least 20% | 2 Participants |
Secondary
Achievement of Partial or Complete Remission of UPCR Through Week 12 and Through the End of Treatment
Partial and complete remission were defined as follows: Partial remission (included all of the following): * Reduction from baseline by ≥50% in urine protein:creatinine ratio (UPCR) * Reduction in UPCR to a level that was \<3.5 g/g * Subject could not have been a treatment failure Complete remission (included all of the following): * Reduction in UPCR to \<0.3 g/g * Serum albumin within normal range * For subjects with abnormal serum creatinine levels at baseline, return to normal levels * For subjects with normal serum creatinine levels at baseline, final value within 20% of baseline levels * Subject could not have been a treatment failure
Time frame: Baseline to week 12
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CCX140-B | Achievement of Partial or Complete Remission of UPCR Through Week 12 and Through the End of Treatment | No Complete or Partial remission at week 12/ end of treatment | 4 Participants |
| CCX140-B | Achievement of Partial or Complete Remission of UPCR Through Week 12 and Through the End of Treatment | Partial remission at Week 12 | 1 Participants |
Secondary
Assessment of Time to and Proportion of Subjects With Achievement of Partial Remission During the Treatment Period
Partial remission is defined as reduction from baseline by ≥50% in UPCR, reduction in UPCR to a level that was \<3.5 g/g.
Time frame: Baseline to week 52
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CCX140-B | Assessment of Time to and Proportion of Subjects With Achievement of Partial Remission During the Treatment Period | Did not achieve partial remission | 4 Participants |
| CCX140-B | Assessment of Time to and Proportion of Subjects With Achievement of Partial Remission During the Treatment Period | Partial remission at Week 12 | 1 Participants |
Secondary
Change From Baseline in Urine Protein:Creatinine Ratio (UPCR) Over Time
Mean change from baseline in urinary protein:creatinine ratio (UPCR) over time.
Time frame: Baseline to week 12 and week 52
Population: Data was not available for all patients at each timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CCX140-B | Change From Baseline in Urine Protein:Creatinine Ratio (UPCR) Over Time | Week 12 | -1.3100 g protein/g creatinine | Standard Deviation 3.76247 |
| CCX140-B | Change From Baseline in Urine Protein:Creatinine Ratio (UPCR) Over Time | Week 52 | -0.4985 g protein/g creatinine | Standard Deviation 3.37926 |
Secondary
Changes to Laboratory Parameters Related to Renal Function Including Serum Albumin, Creatinine, Cystatin C, Urinary Albumin:Creatinine Ratio, Total 24-hour Protein Excretion During the Trial
Changes to laboratory parameters related to renal function including serum albumin, creatinine, cystatin C, urinary albumin:creatinine ratio, total 24-hour protein excretion during the trial
Time frame: Baseline to Day 57
Population: No data collected
Secondary
Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the Overall Trial
Summary of the Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the overall trial EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels. The EQ-5D-5L consists of : the EQ-5D descriptive system. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine.
Time frame: Baseline to Week 12 and Week 52
Population: Data was not available for all patients at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CCX140-B | Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the Overall Trial | Week 12 | 66.3 score on a scale | Standard Deviation 31.98 |
| CCX140-B | Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the Overall Trial | Week 52 | 85 score on a scale | Standard Deviation 0 |
Secondary
Effect of CCX140-B Treatment on Quality of Life Endpoint SF-36V2
Summary of the Effect of CCX140-B Treatment on Quality of Life Endpoints SF-36V2 for the overall trial SF-36v2: Medical Outcomes Survey Short Form-36 version 2. SF-36v2 measures each of the following eight health domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Scores on each item are summed and averaged. The SF-36v2 component domain scores range from 0 (worst health) to 100 (best health).
Time frame: Baseline to Week 52
Population: Due to the small sample size and early termination of the study, no data could be collected
Secondary
Mean Change From Baseline for eGFR CKD-EPI Creatinine-Cystatin C Equation Over Time
CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate;
Time frame: Baseline to Week 12 and Week 52
Population: Data was not available for all patients at each timepoint
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CCX140-B | Mean Change From Baseline for eGFR CKD-EPI Creatinine-Cystatin C Equation Over Time | Week 12 | -2.25 ml/min/1.73 m² |
| CCX140-B | Mean Change From Baseline for eGFR CKD-EPI Creatinine-Cystatin C Equation Over Time | Week 52 | -8.0 ml/min/1.73 m² |
Secondary
Mean Change From Baseline for eGFR Using the CKD-EPI Cystatin C Equation Over Time
eGFR-Estimated Glomerular Filtration Rate;CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration
Time frame: Baseline to Week 12 and Week 52
Population: Data was not available for all patients at each timepoint
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CCX140-B | Mean Change From Baseline for eGFR Using the CKD-EPI Cystatin C Equation Over Time | Week 12 | 7.50 mL/min/1.73m² |
| CCX140-B | Mean Change From Baseline for eGFR Using the CKD-EPI Cystatin C Equation Over Time | Week 52 | -2.00 mL/min/1.73m² |
Secondary
Mean Change From Baseline for the eGFR CKD-EPI Creatinine Equation Over Time
CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate
Time frame: Baseline to Week 12 and Week 52
Population: Data was not available for all patients at each timepoint
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CCX140-B | Mean Change From Baseline for the eGFR CKD-EPI Creatinine Equation Over Time | Week 12 | -14.50 ml/min/1.73 m² |
| CCX140-B | Mean Change From Baseline for the eGFR CKD-EPI Creatinine Equation Over Time | Week 52 | -15.0 ml/min/1.73 m² |
Secondary
Mean Change From Baseline for the MDRD Creatinine Equation Over Time
MDRD = Modification of Diet in Renal Disease. The mean eGFR (using the MDRD Creatinine equation) change from baseline to Week 12 and Week 52
Time frame: Baseline to Week 12 and Week 52
Population: Data was not available for all patients at each timepoint
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CCX140-B | Mean Change From Baseline for the MDRD Creatinine Equation Over Time | Week 12 | -12.75 ml/min/1.73 m² |
| CCX140-B | Mean Change From Baseline for the MDRD Creatinine Equation Over Time | Week 52 | -13.00 ml/min/1.73 m² |
Secondary
Proportion of Subjects With Achievement of Complete Remission During the Treatment Period
Complete remission is defined as reduction in urine protein:creatinine ratio (UPCR) to \<0.3 g/g, normal serum albumin, and normal serum creatinine levels or within 20% of baseline levels.
Time frame: Baseline to week 52
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CCX140-B | Proportion of Subjects With Achievement of Complete Remission During the Treatment Period | Achieved complete remission | 0 Participants |
| CCX140-B | Proportion of Subjects With Achievement of Complete Remission During the Treatment Period | Did not achieve complete remission | 5 Participants |
Secondary
Time Taken of Subjects to Achieve Complete Remission During the Treatment Period
Complete remission is defined as reduction in urine protein:creatinine ratio (UPCR) to \<0.3 g/g, normal serum albumin, and normal serum creatinine levels or within 20% of baseline levels.
Time frame: Baseline to week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CCX140-B | Time Taken of Subjects to Achieve Complete Remission During the Treatment Period | NA days |
Secondary
Time to Rescue Therapy
Based on Investigator or physician initiation of glucocorticoids or new immunosuppressive agents or new major treatment modalities (e.g. plasmapheresis, dialysis)
Time frame: Baseline to week 52
Population: Due to the small sample size and early termination of the study, no data could be collected