A Study of CCX140-B in Subjects With FSGS

NCT ID: NCT03536754

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-17
• Study Completion Date: 2020-02-19

Brief 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

Detailed 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).

Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

Conditions

FSGS; Focal Segmental Glomerulosclerosis; Glomerulosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group A

Placebo (N=10)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Group B

CCX140-B 5 mg once daily (N=10)

Group Type: EXPERIMENTAL

CCX140-B

Intervention Type: DRUG

One 5 mg CCX140-B tablet and 2 placebo tablets in the morning; 3 placebo tablets in the evening; per os, for 84 days.

Group C

CCX140-B 10 mg twice daily (N=10)

Group Type: EXPERIMENTAL

CCX140-B

Intervention Type: DRUG

Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days.

Group D

CCX140-B 15 mg twice daily (N=10)

Group Type: EXPERIMENTAL

CCX140-B

Intervention Type: DRUG

Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.

Interventions

Placebo

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

Intervention Type: OTHER

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.

Intervention Type: DRUG

CCX140-B

Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days.

Intervention Type: DRUG

CCX140-B

Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.

Intervention Type: DRUG

Other Intervention Names

CCX140-B Placebo; Group B; Group C; Group D

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).

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

AKDHC

Phoenix, Arizona, United States

Los Angeles Biomedical Research Institute

Torrance, California, United States

Northwest Louisiana Nephrology

Shreveport, Louisiana, United States

MGH

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

East Carolina University

Greenville, North Carolina, United States

Rhode Island Hospital

Providence, Rhode Island, United States

University of Texas Health Sciences Center

Houston, Texas, United States

Utah Kidney Research Institute

Salt Lake City, Utah, United States

Monash Medical Centre

Clayton, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

Parkville, , Australia

St. Josephs Healthcare - Hamilton

Hamilton, Ontario, Canada

Sunnybrook Health Sciences Centre (Odette Cancer Center)

Toronto, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

CISSS de la Monteregie-Centre - Hopital Charles LeMoyne

Greenfield Park, Quebec, Canada

CHU Bordeaux- Hospital Pellegrin

Bordeaux, , France

CHU Henri Mondor

Créteil, , France

CHU de Grenoble

Grenoble, , France

APHM - Hopital de la Conception

Marseille, , France

Hopitaux Prives de Metz

Metz, , France

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, , Italy

North Shore Hospital

Takapuna, Auckland, New Zealand

Taranaki Base Hospital

New Plymouth, , New Zealand

Uniwersytecki Szpital Kliniczny w Bialymstoku - II Klinika Nefrologii z Oddzialem Leczenia Nadcisnienia Tetniczego i Pododdzialem Dializoterapii

Bialystok, , Poland

SCM Sp. Zo.o.

Krakow, , Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnez Centralny Szpital

Lodz, , Poland

Samodzielny Publiczny Szpital Kliniczny

Szczecin, , Poland

Uniwersytecki Szpital Kliniczny Klinika Nefrologii i Medycyny Transplantacyjnej

Wroclaw, , Poland

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 Kingdom

Countries

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

References

Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.

Reference Type: DERIVED

PMID: 35224732 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CL011_140

Identifier Type: -

Identifier Source: org_study_id

LUMINA-1

Identifier Type: OTHER

Identifier Source: secondary_id

NCT03536754

Identifier Type: OTHER

Identifier Source: secondary_id

134007

Identifier Type: OTHER

Identifier Source: secondary_id