Non-life-threatening anti-neutrophil cytoplasmic antibody vasculitis (AAV) with mild-to-moderate renal involvement MedDRA version: 18.1 Level: PT Classification code 10047115 Term: Vasculitis System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Product Name: CCX168
Product Code: CCX168
Pharmaceutical Form: Capsule
INN or Proposed INN: CCX168
Current Sponsor code: CCX168
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrat
Sponsors
ChemoCentryx, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Clinical diagnosis of granulomatosis with polyangiitis (Wegener’s), microscopic polyangiitis or renal limited vasculitis, consistent with Chapel-Hill consensus definitions 2. Male and postmenopausal (lack of menses for at least 2 years without an alternative explanation) or surgically sterile female subjects, aged at least 18 years, with new (within 4 weeks prior to screening) or relapsed AAV where treatment with cyclophosphamide or rituximab would be required; If female under 50 years, the postmenopausal status should be confirmed by the relevant hormonal test. 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; acceptable methods include combined estrogen and progestogen (oral, intravaginal, or transdermal), or progestogen-only hormonal contraception (oral, injectable, or implantable), intra-uterine device, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence; 3. Positive indirect immunofluorescence (IIF) test for P-ANCA or CANCA, or positive ELISA test for anti-proteinase-3 (PR3) or antimyeloperoxidase (MPO) at screening; If only the IIF assay is positive at screening, and none of the ELISA tests, there must be documentation in the study records of a positive ELISA assay in the past; 4. Have at least one "major" item, or at least 3 non-major items, or at least 2 renal items on the BVAS version 3 (see section 11.3); 5. eGFR =20 mL per minute (MDRD);6.Willing and able to give written Informed Consent and to comply with the requirements of the study protocol 7.Judged to be otherwise healthy by the Investigator, based on medical history, physical examination (including electrocardiogram [ECG]), 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 30
Exclusion criteria
Exclusion criteria: 1.Severe disease as determined by rapidly progressive glomerulonephritis such that commencement of renal replacement therapy could be anticipated within 7 days, alveolar hemorrhage leading to Grade 3 or higher hypoxia (i.e., decreased oxygen saturation at rest, e.g., pulse-oximeter 3000 mg methylprednisolone equivalent, within 12 weeks prior to screening OR >500 mg methylprednisolone equivalent within 4 weeks prior to screening; 6.Have been taking an oral daily dose of a corticosteroid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to the screening visit. If on an oral corticosteriod at a daily dose of more than 10 mg prednisone equivalent at the time of screening, the oral dose needs to be reduced to a daily dose not exceeding 10 mg prednisone equivalent prior to Day 1; 7.Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred (i.e.,CD19 count > 0.01x10^9/L); received anti-TNF treatment, abatacept, alemtuzumab, IVIg, belimumab, tocilizumab, or plasma exchange within 12 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 >100), 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 carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis; 10.Evidence of tuberculosis based on chest X rays performed during screening as part of the BVAS assessment; 11.Positive HBV, HCV, or HIV viral screening test; 12.Any infection requiring antibiotic treatment within 4 weeks prior to screening (except for prophylactic treatment for Pneumocystis carinii pneumonia [PCP] or treatment for suspected infection that instead turns out ot be a consequence of ANCA vasculitis e.g., pneumonitis); 13.Received a live vaccine within 4 weeks of screening; 14.WBC count less than 4000/uL or neutrophil count less than 2000/uL, or lymphocyte count less than 1000/uL 15.Hemoglobin less than 9 g/dL (or 5.56 mmol/L) at screening; 16.Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin > 3 x the upper limit of normal; 17.Prothrombin time (PT) or partial throm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: the primary safety objective is to evaluate the safety and tolerability of CCX168 in subjects with AAV on background cyclophosphamide or rituximab treatment. Primary efficacy objective is to evaluate the efficacy of CCX168 based on the Birmingham Vasculitis Activity Score (BVAS);Secondary Objective: 1. Evaluation of the efficacy of CCX168 compared to standard of care (SOC) based on changes in renal disease activity parameters: a. eGFR (MDRD serum creatinine equation); b. Hematuria (central laboratory microscopic count of urinary RBCs); and c. Albuminuria (first morning urinary albumin:creatinine ratio); 2. Assessment of changes in renal inflammatory activity based on urinary monocyte chemoattractant protein-1 (MCP 1):creatinine ratio and serum C-reactive protein concentration 3. Assessment of the feasibility of reducing or eliminating the use of corticosteroids in the treatment of subjects with ANCA-associated vasculitis (AAV) without the need for rescue corticosteroid measures 4. Assessment of health-related quality-of-life changes based on SF- 36v2 and EQ-5D-5L 5. Assessment of changes in VDI 6. Assessment of changes in ANCA 7. Assessment of changes in pharmacodynamics markers in plasma and urine ; 8. Evaluation of the pharmacokinetic profile of CCX168;Primary end point(s): The primary safety endpoint is the subject incidence of adverse events. the primary efficacy endpoint is BVAS response;Timepoint(s) of evaluation of this end point: Day 85 and Day169 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety 1. Adverse events associated with glucocorticoids. 2.Subject incidence of infections, serious infections, severe infections (i.e., Grade 3), and infections leading to subject withdrawal from the study; 3.Change from baseline in all safety laboratory parameters; 4.Change from baseline in vital signs; 5.Incidence of clinically significant ECG changes from baseline. Efficacy: 1. Renal response 2. BVAS remission 3. eGFR 4. Hematuria 5. Albuminuria 6. Urinary MCP-1 7. CRP 8. Steroid rescue events 9. VDI 10. SF-36v2 and EQ-5D-5L;Timepoint(s) of evaluation of this end point: Day 85 and Day169 | — |
Countries
Austria, Belgium, Czech Republic, Germany, Hungary, Ireland, Netherlands, Poland, Sweden, United Kingdom
Contacts
Public ContactAntonia Potarca
ChemoCentryx, Inc.
Outcome results
None listed