A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome

Focal Segmental Glomerulosclerosis Clinical Trial

Official title:

An Open Label, Intra-Subject Dose Escalation Study of CCX140-B in Subjects With Primary Focal Segmental Glomerulosclerosis (FSGS) and Nephrotic Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03703908
• Other study ID #: CL012_140
• Secondary ID: LUMINA-2
• Status: Terminated
• Phase: Phase 2
• Start date: October 1, 2018
• Est. completion date: June 24, 2020

Study information

• Verified date: January 2024
• Source: ChemoCentryx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An Open Label, Intra-Subject Dose Escalation Study of CCX140 B in Subjects with Primary FSGS and Nephrotic Syndrome

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: June 24, 2020
• Est. primary completion date: June 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Focal Segmental Glomerulosclerosis
• Glomerulosclerosis, Focal Segmental
• Nephrosis
• Nephrotic Syndrome

Intervention

Drug:
• CCX140-B
Orally administered tablet

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Minnesota	Minneapolis	Minnesota
United States	Utah Kidney Research Institute	Salt Lake City	Utah
United States	Northwest Louisiana Nephrology	Shreveport	Louisiana
United States	Los Angeles Biomedical Research Institute	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
ChemoCentryx

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline to week 12
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	Baseline to week 12
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.	Baseline to week 52
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.	Baseline to week 52
Secondary	Change From Baseline in Urine Protein:Creatinine Ratio (UPCR) Over Time	Mean change from baseline in urinary protein:creatinine ratio (UPCR) over time.	Baseline to week 12 and week 52
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.	Baseline to week 52
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)	Baseline to week 52
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	Baseline to Week 12 and Week 52
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	Baseline to Week 12 and Week 52
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;	Baseline to Week 12 and Week 52
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	Baseline to Week 12 and Week 52
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).	Baseline to Week 52
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.	Baseline to Week 12 and Week 52
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	Baseline to Day 57