A Study of CCX140-B in Subjects With FSGS
Condition: FSGS; Focal Segmental Glomerulosclerosis; Glomerulosclerosis
MeSH terms: Glomerulosclerosis, Focal Segmental
Intervention: Placebo; CCX140-B; CCX140-B; CCX140-B
Intervention description: Three placebo tablets, taken twice daily (BID), per os, for 84 days (12 weeks); One 5 mg CCX140-B tablet and 2 placebo tablets in the morning; 3 placebo tablets in the evening; per os, for 84 days.; Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days.; Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Randomized, placebo-controlled, Phase 2
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Double-blind
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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).

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