A Study of CCX140-B in Subjects With FSGS

• Register: ClinicalTrials.gov
• Last refreshed on: 19 December 2023
• Main ID: NCT03536754
• Date of registration: 28/03/2018
• Prospective Registration: Yes
• Primary sponsor: ChemoCentryx
• Public title: A Study of CCX140-B in Subjects With FSGS
• Scientific 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)
• Date of first enrolment: May 17, 2018
• Target sample size: 46
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03536754
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: Peter Staehr, MD
• Affiliation: ChemoCentryx

Key inclusion & exclusion 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).

-



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Glomerulosclerosis

Focal Segmental Glomerulosclerosis

FSGS

Intervention(s)

Other: Placebo

Drug: CCX140-B

Primary Outcome(s)

Change From Baseline in Hemoglobin [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Phosphate [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Prothrombin Intl. Normalised Ratio [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Prothrombin Time [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Activated Partial Thromboplastin Time [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Basophils/Leukocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Basophils [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Hematocrit [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Eosinophils [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Bilirubin [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Creatinine [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Lactate Dehydrogenase [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Indirect Bilirubin [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Eosinophils/Leukocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Lymphocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma C Reactive Protein [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Erythrocyte Mean Corpuscular Volume [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Monocytes/Leukocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Lymphocytes/Leukocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Alanine Aminotransferase [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Amylase [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Calcium [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Bicarbonate [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Urea Nitrogen [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Cholesterol [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Chloride [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Creatine Kinase [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Cystatin C [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Triglycerides [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Alkaline Phosphatase [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma LDL Cholesterol [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Direct Bilirubin [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Urine Protein [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Glucose [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma HDL Cholesterol [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Urate [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Magnesium [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Platelets [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Pancreatic Lipase [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) [Time Frame: Baseline to Week 12, and Week 12 to Week 24]

Change From Baseline in Plasma Protein [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Urine Albumin [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in UPCR at Week 12 [Time Frame: Baseline to Week 12]

Change From Baseline in Urine Creatinine [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Erythrocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Leukocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Neutrophils [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Neutrophils/Leukocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Aspartate Aminotransferase [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Potassium [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Plasma Sodium [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Change From Baseline in Reticulocytes/Erythrocytes [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Secondary Outcome(s)

Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 [Time Frame: Endpoint at Week 12 for Double-Blind Treatment Period and Endpoint at Week 24 for Open-Label Extension]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 [Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)]

Secondary ID(s)

LUMINA-1

134007

CL011_140

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/12/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03536754