A controlled study to evaluate the safety and efficacy of the study drug, CCX140-B, in subjects with Focal Segmental Glomerulosclerosis (a type of glomerular disease)

• Register: EUCTR
• Last refreshed on: 13 July 2020
• Main ID: EUCTR2017-003021-15-PL
• Date of registration: 18/05/2018
• Prospective Registration: Yes
• Primary sponsor: ChemoCentryx, Inc.
• Public title: A controlled study to evaluate the safety and efficacy of the study drug, CCX140-B, in subjects with Focal Segmental Glomerulosclerosis (a type of glomerular disease)
• 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: 19/06/2018
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003021-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Dose Ranging If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Czech Republic, France, Germany, Italy, New Zealand, Poland, United Kingdom, United States

Contacts

• Name: Regulatory Submissions
• Affiliation: Medpace Germany GmbH

• Name: Regulatory Submissions
• Affiliation: Medpace Germany GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects aged 18-75 years inclusive
2. Urinary total protein:creatinine ratio (UPCR) = 1 g protein/g creatinine at screening (or UPCR at 113 mg/mmol).
3. Diagnosis of FSGS based on at least one of the following:
o Renal biopsy demonstrating the FSGS lesion and characteristic clinical presentation and course
o High risk genetic variant and characteristic clinical presentation and course
4. Diagnosis of one of the following subtypes of FSGS:
o Primary FSGS based on characteristic histopathology, medical history, and clinical course, or
o FSGS secondary to a genetic variant associated with increased risk or severity, which may include NPHS1, NPHS2, WT-1, LAMB2, CD2AP, TRPC6, ACTN4 or INF2
5. Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73m2, with eGFR calculated
using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (using creatinine or cystatin C)
6. The typical blood pressure of the patient should be clinically stable prior to enrollment and not exceed 145/95 mmHg.
7. If using RAAS blockers, dose must be stable for a minimum of 4 weeks prior to Screening, and projected to remain stable through Study Week 12, unless adjustment is required for management of hypertension. Blood pressure should be clinically stable prior to enrollment.
8. If using immunosuppressive or immunomodulatory therapy, dose must be stable for a
minimum of 4 weeks prior to Screening, and projected to remain stable through Study
Week 12
9. If using glucocorticoids, dose must be stable for a minimum of 4 weeks prior to Screening and projected to remain stable through Study Week 12
10. Female subjects of childbearing potential may participate if adequate contraception is used during, and for at least 1 month after last dose of study drug. Male subjects with partners of childbearing potential may participate in the study if they had a vasectomy at least 6 months prior to randomization or if adequate contraception is used during, and for at least one month after the last dose of study drug. Adequate contraception is defined as resulting in a failure rate of less than 1% per year (combined estrogen and progestogen [oral, intravaginal, or transdermal], or progestogen-only hormonal contraception (oral, injectable, or implantable), intra-uterine device, intra-uterine hormone releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence). In addition, a barrier method (i.e. cervical cap, diaphragm or condom) must be used during intercourse between a male subject and a female of child-bearing potential.
11. Willing and able to give written Informed Consent and to comply with the requirements
of the study protocol
12. Judged to be otherwise fit for the study by the Investigator, based on medical history,
physical examination, and clinical laboratory assessments. Subjects with clinical laboratory values that are outside of normal limits (other than those specified in the Exclusion Criteria) and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance, may be entered into the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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. Subjects who used of rituximab or other B-cell depleting monoclonal antibodies within 20 weeks prior to screening are excluded while subjects that used rituximab or other B-cell depleting monoclonal antibodies prior to 20 week of screening are allowed with confirmed recovery of the B-cell population to within normal range at the time of screening
5. Plasmapheresis within 12 weeks prior to screening
6. Body mass index (BMI) =40
7. Participated in any clinical study of an investigational product within 12 weeks prior to
screening, or within 5 half-lives after taking the last dose of investigational product
8. Currently on dialysis or likely to require dialysis during the projected blinded treatment
period of 12 weeks
9. History or presence of any form of cancer within the 5 years prior to screening, with the
exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ
such as cervical or breast carcinoma in situ that has been excised or resected completely and
is without evidence of local recurrence or metastasis
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 (e.g. lupus nephritis, C3 glomerulopathy, proliferative glomerulonephritis, IgA nephropathy, reflux nephropathy,
surgical segmental renal ablation, sickle cell disease ) that is active, or has significant risk of
progressing during the course of the study
12. Disorders other than those listed in Inclusion Criterion 4 that are associated with FSGS
lesion (i.e. secondary FSGS such as single kidney, surgical segmental renal ablation, sickle cell disease, diabetic
nephropathy; others) or histological collapsing variant subtypes of FSGS
13. Evidence of tuberculosis based on interferon ? release assay (IGRA) within 6 weeks prior to screening
14. Evidence of hepatic disease; AST, ALT, alkaline phosphatase >3x ULN, or total bilirubin > 2x ULN or INR > 1.5 x ULN at screening 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. Clinically significant peripheral neuropathy.
16. Hematologic abnormalities as follows: Hb < 8 g/dL, platelets < 50,000, ANC < 1000
cells/µL) at baseline
17. Clinically significant abnormal ECG during screening, e.g., QTcF greater than 450 msec
18. History of alcohol or illicit drug abuse. Recreational use of cannabis is not excluded where legal.
19. History of gastrointestinal conditions that may interfere with study medication compliance, e.g., severe gastroparesis, with regurgitation of food or oral medication
20. Known hypersensitivity to CCX140-B or inactive ingredients of the CCX140-B tablets
(including microcrystalline cellulose, starch, crospovidone, magnesium stearate, or silicon
dioxide, or tartrazine)
21. 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
gluco

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Focal Segmental Glomerulosclerosis (FSGS)
MedDRA version: 20.0 Level: PT Classification code 10067757 Term: Focal segmental glomerulosclerosis System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Code: CCX140-B
Pharmaceutical Form: Tablet
INN or Proposed INN: INN not available yet
Current Sponsor code: CCX140-B
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To evaluate the effect of CCX140-B on renal function, as assessed by estimated glomerular filtration rate (eGFR) at Week 12 and 24;
• To evaluate the effect of CCX140-B treatment on fraction of subjects achieving complete and partial renal remission (by 2 different partial remission definitions)
• To evaluate the pharmacokinetic (PK) profile of CCX140-B in subjects with FSGS.

Main Objective: • The primary safety objective of this study is to evaluate the safety and tolerability of CCX140-B in subjects with FSGS with proteinuria.
• The primary efficacy objective of this study is to evaluate the effect of CCX140-B treatment on urinary protein excretion in subjects with FSGS, as assessed by change from baseline in the urine protein to creatinine ratio (UPCR).

Timepoint(s) of evaluation of this end point: Efficacy:
Week 12, Week 24
Safety:
Day1, Week12, Week16, Week24, Week28

Primary end point(s): Efficacy:
Change from baseline in urine protein:creatinine ratio (UPCR) at week 12
Safety:
• Subject incidence of treatment-emergent adverse events, adverse events leading to study
withdrawal, and serious adverse events;
• Change from baseline and shifts from baseline in all safety laboratory parameters;
• Change from baseline in vital signs;
• Change form baseline in score on the ACTG BPNST
• Clinically significant abnormal ECG findings
• Physical examinations

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Efficacy: Weeks 12, Week 24

Secondary end point(s): Efficacy:
• 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
• Proportion of subjects achieving complete renal remission at Weeks 12
and 24 Completed Remission (includes 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 that age group
- For subjects with normal serum creatinine levels at baseline, final
value within 20% of baseline levels
• Proportion of subjects achieving partial remission at Weeks 12 and 24
by the following two different definitions:
- UPCR reduction of = 50% from baseline and UPCR <3.5g/g
- decrease in UPCR to less than 1.5 g/g and at least a 40% reduction in
proteinuria from baseline

Secondary ID(s)

CL011_140

134007

2017-003021-15-FR

Source(s) of Monetary Support

ChemoCentryx, Inc.

Ethics review

Status: Approved
Approval date: 15/05/2018
Contact: