An open-label phase 2 study to evaluate the safety and efficacy of CCX168 in subjects with IgA Nephropathy on stable RAAS blockade.

• Register: EUCTR
• Last refreshed on: 26 February 2018
• Main ID: EUCTR2014-003402-33-SE
• Date of registration: 29/12/2014
• Prospective Registration: Yes
• Primary sponsor: ChemoCentryx, Inc.
• Public title: An open-label phase 2 study to evaluate the safety and efficacy of CCX168 in subjects with IgA Nephropathy on stable RAAS blockade.
• Scientific title: An open-label phase 2 study to evaluate the safety and efficacy of CCX168 in subjects with IgA Nephropathy on stable RAAS blockade.
• Date of first enrolment: 12/02/2015
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003402-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Sweden, United States

Contacts

• Name: Clinical Operations Manager
• Affiliation: ChemoCentryx, Inc.

• Name: Clinical Operations Manager
• Affiliation: ChemoCentryx, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Biopsy-proven IgAN performed for clinical purposes within 3 years prior to screening
2. eGRF>60 mL/min/1.73 m² (by MDRD equation) OR eGFR >45 mL/min/1.73 m² if eGFR has not declined < 10 mL/min/1.73 m² over the previous 24 weeks
3. Proteinuria, defined as first morning urinary PCR > 1g/g creatinine
4. Male or female subjects, aged at least 18 years; where allowed by local regulations, female subjects of childbearing potential may participate if adequate contraception is used during, and for at least the three months after study completion; 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 the three months after study completion; 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)
5. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol
6. Judged to be otherwise healthy 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 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Severe renal disease as determined by rapid decline in eGFR (defined as > 10 mL/min/1.73m² over 24 weeks prior to screening, not otherwise explained)
2. Pregnant or nursing
3. Proteinuria > 8 g/day (or>8g/g creatinine)
4. Patients with systemic manifestations of Henoch-Schönlein purpura within the last 2 years prior to screening.
5. Patients with IgAN deemed secondary to underlying disease: e.g., diabetes, liver disease, cirrhosis, celiac disease, HIV, inflammatory bowel disease, lymphoma, or associated with any other multi-system autoimmune disease
6. Biopsy report demonstrating severe crescentic IgAN (>25% crescents), OR>50% interstitial fibrosis and/or tubular atrophy ("T2") (Cattran et al. 2009), OR a high likelihood of rapid decline in eGFR based on an MEST ("Oxford") classification (M=mesangial hypercellularity; E=endocapillary proliferation; S=segmental glomerulosclerosis/adhesion; T=tubular atrophy/interstitial fibrosis) score of M1, E0, T1, or M0/1, E1, T1 (Cattran et al. 2009)
7. History of treatment with glucocorticoids, cyclophosphamide, azathioprine, mycophenolate mofetil, or any biologic immunomodulatory agent within the 24 weeks prior to screening
8. Symptomatic congestive heart failure requiring prescription medication, clinically evident peripheral edema of cardiac origin, poorly-controlled hypertension (systolic blood pressure>160 or diastolic blood pressure >95), history of unstable angina, myocardial infarction or stroke within 6 months prior to screening
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 cervical carcinoma in situ or breast cacrinoma in situ that has been excised or resected completely and is without evidene of local recurrence or metastasis
10. Positive HBV, HCV, or HIV viral screening test
11. History of tuberculosis
12. Any infection requiring antibiotic treatment that has not cleared prior to starting CCX168 treatment on Day 1;
13. WBC count less than 4000/uL, or neutrophil count less than 2000/uL, or lymphocyte count less than 1000/uL
14. Hemoglobin less than 9 g/dL (or 5.56 mmol/L) at screening
15. Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin > 3 x the upper limit of normal
16. Participated in any clinical study of an investigational product within 30 days prior to screening or within 5 half-lives after taking the last dose
17. History of presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation



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

Health Condition(s) or Problem(s) studied

IgAN is reported as the most common glomerulonephritis worldwide. It is associated with a wide spectrum of disease severity and rate of progression of renal failure.
MedDRA version: 17.1 Level: PT Classification code 10021263 Term: IgA nephropathy System Organ Class: 10038359 - Renal and urinary disorders

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

Intervention(s)

Product Name: CCX168
Pharmaceutical Form: Capsule, hard
Current Sponsor code: CCX168
Other descriptive name: CCX168
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10mg per capsule-

Primary Outcome(s)

Main Objective: The primary safety objective of this study is to evaluate the safety and tolerability of CCX168 in subjects with igAN on background supportive therapy with a maximally tolerated dose of RAAS blockade.
The primary efficacy objective is to evaluate the efficacy of CCX168 based on an improvement in proteinuria.

Primary end point(s): The primary safety endpoint is the subject incidence of adverse events. The primary efficacy endpoint is the change in slope of first morning urinary PCR from the 8-week RAAS blocker run-in period to the 12-week CCX168 treatment period

Secondary Objective: 1. Change in albuminuria with CCX168 treatment
2. Change in renal function based on eGFR with CCX168 treatment
3. Change in hematuria with CCX168 treatment
4. Change in renal inflammatory activity based on urinary monocyte chemoattractant protein-1 (MCP 1):creatinine ratio and urinary epidermal growth factor (EGF):MCP-1 ratio with CCX168 treatment
5. Change in serum IgA: plasma C3 ratio with CCX168 treatment
6. Changes in pharmacodynamic markers in plasma and urine with CCX168 treatment, e.g., C3a, C5a, properdin, and sC5b-9

Timepoint(s) of evaluation of this end point: Day85

Secondary Outcome(s)

Secondary end point(s): Safety: 1. Change from baseline in all safety laboratory parameters
2. Change from baseline in vital signs
Efficacy: 1. The proportion of subjects achieving renal response, defined as an improvement in proteinuria based on a decrease from baseline to Day 85 in proteinuria to a level < 300mg/g creatinine and maintaining estimated glomerular filtration rate (eGFR) within 15% of baseline
2. The proportion of subjects achieving a partial renal response, defined as an improvement in proteinuria based on a decrease from baseline to Day 85 in proteinuria to a level <1g/g creatinine and maintinaing estimated glomerular filtration rate (eGFR) within 15% of baseline
3. Change in slope from the run-in period to the treatment period for urinary ACR, eGFR, urinary MCP-1: creatinine, urinary EGF:MCP-1, and urinary microscopic RBC counts
4. The percent change from baseline to Day 85 in urinary PCR and ACR
5. The change from baseline to Day 85 in eGFR
6. In patients with hematuria at baseline, the percent change from baseline in urinary RBC count
7. The percent change from baseline to Day 85 in urinary MCP-1: creatinine ratio
8. The percent change from baseline to Day 85 in serum IgA:plasma C3 ratio
9. The percent change from baseline to Day 85 in urinary EGF:MCP-1 ratio
10. The percent change from baseline in plasma and urinary biomarker, e.g., C3a, C5a, properdin, and sC5b-9

Timepoint(s) of evaluation of this end point: Changes from baseline in all efficacy measurements at time points other than day 85 will also be assessed.

Secondary ID(s)

CL005_168

2014-003402-33-BE

123187

Source(s) of Monetary Support

ChemoCentryx, Inc.