A Study of CCX140-B in Subjects With FSGS

Focal Segmental Glomerulosclerosis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects With Focal Segmental Glomerulosclerosis (FSGS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03536754
• Other study ID #: CL011_140
• Secondary ID: LUMINA-1134007
• Status: Completed
• Phase: Phase 2
• Start date: May 17, 2018
• Est. completion date: February 19, 2020

Study information

• Verified date: November 2023
• Source: ChemoCentryx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects with FSGS to be conducted in the North America, Europe and Australia

Description:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects with Focal Segmental Glomerulosclerosis (FSGS) to be conducted in the North America, Europe and Australia. The aim of this study is to evaluate the effect of treatment with CCX140-B, a selective antagonist of C-C chemokine receptor type 2 in subjects with focal segmental glomerulosclerosis on urinary protein excretion as assessed by changes in urine protein to creatinine ratio (UPCR)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: February 19, 2020
• Est. primary completion date: February 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female subjects aged 18-75

2. UPCR = 1 g protein/g creatinine (or at 113 mg.mmol) at screening

3. Diagnosis of FSGS based on renal biopsy or high risk genetic variant

4. Diagnosis of one of primary FSGS based on characteristic histopathology, medical history and clinical course or FSGS secondary to genetic variants associated with increased risk or severity.

5. Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73m2

6. Clinical stable blood pressure not to exceed 145/95 mmHg

7. RAAS blockers must be stable for at least 4 weeks prior to screening and projected to remain stable through week 12, unless adjustments are required for management of hypertension.

8. Immunosuppressive or immunomodulatory therapy must be stable for at least 4 weeks prior to screening and projected to remain stable through study week 12

9. Glucocorticoids must be stable for at least 4 weeks prior to screening and projected to remain stable through study week 12.

10. Both genders of childbearing potential must agree to use adequate contraception during and for at least 3 months after the last dose of study drug.

11. Subjects must be willing and able to give written Informed Consent and to comply with protocol requirements.

12. Subjects must be judged to be otherwise fit for the study by the Investigator. -

Exclusion Criteria:

1. Pregnant or nursing

2. History of organ transplantation

3. On an organ transplant waiting list or anticipated organ transplant within 6 months of screening

4. Anti-CD20 monoclonal antibodies within 20 months of screening are exclusionary. Subjects that used anti CD20 monoclonal antibodies prior to week 20 are allowed with confirmed recovery of CD20+ B cell population to within normal range

5. Plasmapheresis within 12 weeks of screening

6. BMI =40

7. Participation in any clinical study of an investigational product within 12 weeks or 5 half-lives of screening

8. Currently on dialysis or likely to require dialysis during the blinded treatment phase of the study.

9. History or presence of any form of cancer within 5 years of screening except excised basal cell or squamous cell carcinoma or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or completed resected without evidence or recurrence.

10. Positive HBV, HCV, or HIV viral screening test. Subjects who have received highly effective therapy for HCV demonstrated to have negative viral titers for at least 6 months following discontinuation of treatment, will be considered to have a negative HCV screening test

11. Renal disease associated with disorders other than FSGS that is active or has significant risk of progressing during the course of the study.

12. Disorders that are associated with FSGS lesions.

13. Evidence of tuberculosis.

14. Evidence of hepatic disease with the exception that isolated INR elevation in the absence of other significant liver enzyme abnormalities is explained by anticoagulant therapy, (e.g. warfarin)

15. Hematologic abnormalities as follows: Hb <8 g/dL, platelets <50,000, ANC <1000 cells/µL) at baseline.

16. QTcF greater than 450 msec.

17. History of alcohol or illicit drug abuse or of lithium, pamidronate and interferon. Recreational use of cannabis is not excluded where legal.

18. History of gastrointestinal conditions that may interfere with study medication compliance.

19. Known hypersensitivity to CCX140-B or inactive ingredients of the CCX140-B tablets (including microcrystalline cellulose, starch, crospovidone, magnesium stearate, or silicon dioxide).

20. History or presence of systemic disorder other than FSGS that requires, or is expected to require, systemic glucocorticoids or immune modulators during the study; topical or inhaled glucocorticoids and immune modulators are not excluded.

21. History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation.

22. Subjects taking strong CYP3A4 inducers or strong CYP3A4 inhibitors within two weeks prior to screening.

23. Subjects taking lithium or interferon; subjects taking non-steroidal anti-inflammatory agents (NSAIDS) chronically (intermittent, i.e. occasional NSAIDS for pain or fever is discouraged, but is not excluded). -

Related Conditions & MeSH terms

• Focal Segmental Glomerulosclerosis
• FSGS
• Glomerulosclerosis
• Glomerulosclerosis, Focal Segmental

Intervention

Other:
• Placebo
Three placebo tablets, taken twice daily (BID), per os, for 84 days (12 weeks)

Drug:
• CCX140-B
One 5 mg CCX140-B tablet and 2 placebo tablets in the morning; 3 placebo tablets in the evening; per os, for 84 days.
• CCX140-B
Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days.
• CCX140-B
Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Melbourne Hospital	Parkville
Canada	CISSS de la Monteregie-Centre - Hopital Charles LeMoyne	Greenfield Park	Quebec
Canada	St. Josephs Healthcare - Hamilton	Hamilton	Ontario
Canada	Sunnybrook Health Sciences Centre (Odette Cancer Center)	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
France	CHU Bordeaux- Hospital Pellegrin	Bordeaux
France	CHU Henri Mondor	Créteil
France	CHU de Grenoble	Grenoble
France	CHU de Grenoble	Grenoble cedex 9
France	APHM - Hopital de la Conception	Marseille
France	Hopitaux Prives de Metz	Metz
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII	Bergamo
Italy	IRCCS Azienda Ospedaliera Universitaria San Martino IST	Genova
Italy	Presidio Ospedaliero di Montichiari-A.O. Spedali Civili di Brescia	Montichiari
Italy	Fondazione S. Maugeri IRCCS	Pavia
Italy	Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
New Zealand	Taranaki Base Hospital	New Plymouth
New Zealand	North Shore Hospital	Takapuna	Auckland
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku - II Klinika Nefrologii z Oddzialem Leczenia Nadcisnienia Tetniczego i Pododdzialem Dializoterapii	Bialystok
Poland	SCM Sp. Zo.o.	Kraków
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnez Centralny Szpital	Lódz
Poland	Samodzielny Publiczny Szpital Kliniczny	Szczecin
Poland	Uniwersytecki Szpital Kliniczny Klinika Nefrologii i Medycyny Transplantacyjnej	Wroclaw
United Kingdom	Cambridge University - Addenbrooke's Hospital	Cambridge
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Salford Royal NHS Foundation Trust Manchester	Salford
United Kingdom	Morriston Hospital	Swansea
United States	MGH	Boston	Massachusetts
United States	East Carolina University	Greenville	North Carolina
United States	University of Texas Health Sciences Center	Houston	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	AKDHC	Phoenix	Arizona
United States	Rhode Island Hospital	Providence	Rhode Island
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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Italy,  New Zealand,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in UPCR at Week 12	Least squared mean ratio of UPCR (Urine protein g:creatinine g) compared to baseline at Week 12 in the ITT population. ITT- Intent to treat	Baseline to Week 12
Primary	Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs)	TEAEs leading to study withdrawal means study drug discontinuation in this endpoint.	Baseline to Week 12, and Week 12 to Week 24
Primary	Change From Baseline in Activated Partial Thromboplastin Time	Normal Range: 23.9 - 40.0	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Alanine Aminotransferase	Normal Range: 6 - 41 U/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Alkaline Phosphatase		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Amylase	Normal range: 22-123 U/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Aspartate Aminotransferase	Normal range : 9-34 U/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Bicarbonate	Normal range: 21-33 mmol/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Bilirubin	Normal range: 0.1-1.10 mg/dL	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma C Reactive Protein	Normal range: 0.0-3.0 mg/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Calcium	Normal range: 8.5-10.5 mg/dL	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Chloride	Normal range: 95-110 mmol/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Cholesterol	Normal range: 100-200 mg/dL	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Creatine Kinase	Normal range: 23-210 U/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Creatinine	Normal range: 0.62-1.44 mg/dL	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Cystatin C	Normal range: 0.53-0.95 mg/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Direct Bilirubin		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Glucose		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma HDL Cholesterol	HDL -High-density lipoprotein	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Indirect Bilirubin		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma LDL Cholesterol	LDL - Low-density lipoprotein	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Lactate Dehydrogenase		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Pancreatic Lipase		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Magnesium		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Phosphate		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Potassium		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Protein		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Prothrombin Intl. Normalised Ratio		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Prothrombin Time		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Sodium		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Triglycerides		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Urate		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Plasma Urea Nitrogen		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Basophils		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Basophils/Leukocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Eosinophils		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Eosinophils/Leukocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration	HGB - Hemoglobin	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Erythrocyte Mean Corpuscular Volume		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Erythrocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Hematocrit		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Hemoglobin		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Leukocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Lymphocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Lymphocytes/Leukocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Monocytes/Leukocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Neutrophils		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Neutrophils/Leukocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Platelets		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Reticulocytes/Erythrocytes		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Urine Albumin		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Urine Creatinine		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Primary	Change From Baseline in Urine Protein		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Secondary	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24	Change from baseline in eGFR calculated by the CKD-EPI Cystatin C equation, CKD-EPI Creatinine equation, CKD-EPI Creatinine-Cystatin C equation and MDRD Creatinine equation at Weeks 12 and 24. CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; MDRD: Modification of Diet in Renal Disease Open label extension covers Baseline to Week 12 and Baseline to Week 24	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Secondary	Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24	1. Proportion of subjects achieving complete renal remission by the following definition at Weeks 12 and 24 o Reduction in UPCR to <0.3 g/g o Serum albumin within normal range (for subjects with abnormal serum creatinine levels at baseline, return to normal levels for that age group; for subjects with normal serum creatinine levels at baseline, final value within 20% of baseline levels) 2. Proportion of subjects achieving partial remission defined as UPCR reduction of =50% from baseline and UPCR <3.5 g/g (definition 1), assessed at Weeks 12 and 24 3. Proportion of subjects achieving partial remission defined Decrease in UPCR to less than 1.5 g/g and at least a 40% reduction in proteinuria from baseline (definition 2), assessed at Weeks 12 and 24	Endpoint at Week 12 for Double-Blind Treatment Period and Endpoint at Week 24 for Open-Label Extension