A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis

Vasculitis Clinical Trial

Official title:

Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis on Background of Cyclophosphamide or Rituximab Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01363388
• Other study ID #: CL002_168
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: January 2016

Study information

• Verified date: March 2024
• Source: ChemoCentryx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this trial is to optimize the treatment to induce remission for patients with non-life-threatening anti-neutrophil cytoplasmic antibody vasculitis (AAV). The intent is to reduce the toxicity of induction therapy by reducing the overall exposure to or eliminating entirely the use of systemic corticosteroids during the induction period with an inhibitor of the complement C5a receptor plus cyclophosphamide or rituximab.

Description:

The primary safety objective of this study is to evaluate the safety and tolerability of CCX168 in subjects with AAV on background cyclophosphamide or rituximab treatment. The primary efficacy objective is to evaluate the efficacy of CCX168 based on the Birmingham Vasculitis Activity Score (BVAS) version 3. The secondary objectives of this study include assessment of the feasibility of reducing or eliminating the use of corticosteroids in the treatment of subjects with ANCA-associated vasculitis without the need for rescue corticosteroid measures and the effect of CCX168 on several disease parameters.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: January 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Clinical diagnosis of granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis or renal limited vasculitis
• Male and postmenopausal or surgically sterile female subjects aged at least 18 years with new or relapsed AAV where treatment with cyclophosphamide or rituximab would be required
• Positive indirect immunofluorescence (IIF) test for P-ANCA or C-ANCA, or positive ELISA test for anti-proteinase-3 (PR3) or anti-myeloperoxidase (MPO) at screening
• Estimated glomerular filtration rate (eGFR) = 20mL/min
• Have at least one "major" item, or at least 3 non-major items, or at least 2 renal items on the BVAS version 3

Key Exclusion Criteria:

• Severe disease as determined by rapidly progressive glomerulonephritis, alveolar hemorrhage, hemoptysis, rapid-onset mononeuritis multiplex or central nervous system involvement
• Any other multi-system autoimmune disease
• Medical history of coagulopathy or bleeding disorder
• Received cyclophosphamide within 12 weeks of screening; if on azathioprine, mycophenolate mofetil or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1
• Received high-dose intravenous corticosteroids within 4 weeks of screening
• On an oral dose of a corticosteroid of more than 10mg prednisone-equivalent at the time of screening
• Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred; received anti-TNF treatment, abatacept, alemtuzumab, IVIg or plasma exchange within 12 weeks of screening

Related Conditions & MeSH terms

• Vasculitis

Intervention

Drug:
• Placebo
BID for 84 days
• CCX168
BID for 84 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ChemoCentryx

Countries where clinical trial is conducted

Austria,  Belgium,  Czechia,  France,  Germany,  Hungary,  Netherlands,  Poland,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Subjects Achieving Disease Response at Day 85	Disease response is defined as BVAS percentage reduction from baseline of at least 50% plus no worsening in any body system component.	Baseline to Day 85
Secondary	Proportion of Patients Achieving Renal Response at Day 85	Renal response, assessed in patients with hematuria and albuminuria at baseline, and defined as an improvement in renal parameters, i.e., an increase from baseline to Day 85 in eGFR (Estimated glomerular filtration rate), MDRD (Modification of Diet in Renal Disease), serum creatinine equation, a decrease from baseline to Day 85 in haematuria (central laboratory microscopic count of urinary red blood cells) , decrease from baseline to Day 85 in albuminuria count (first morning UACR (urinary albumin:creatinine ratio).	Baseline to Day 85
Secondary	Proportion of Subjects Achieving Disease Remission at Day 85	Disease remission is defined as BVAS (Birmingham Vasculitis Activity Score) of 0 or 1 plus no worsening in eGFR (Estimated glomerular filtration rate) and urinary RBC (Red Blood cell) count <10/high power field (hpf)	Day 85
Secondary	Percent Change From Baseline to Day 85 in BVAS	Percent change in Burmingham Vasculitis Index Score (BVAS) at week 12, higher percentage change indicates worse outcome; BVAS = Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health). A negative percentage change indicated improvement in health.	Baseline to Day 85
Secondary	Change From Baseline to Day 85 in eGFR	eGFR (Estimated glomerular filtration rate) based on the MDRD (Modification of Diet in Renal Disease) formula using serum creatinine	Baseline to Day 85
Secondary	Percent Change From Baseline to Day 85 in eGFR	eGFR (Estimated glomerular filtration rate) based on the MDRD (Modification of Diet in Renal Disease) formula using serum creatinine	Baseline to Day 85
Secondary	Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period	In subjects with baseline hematuria >5 RBCs/hpf (Red Blood Cell/High Power Field)	Baseline to Day 85
Secondary	Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period	In subjects with baseline hematuria <=5 RBCs/hpf (Red Blood Cell/High Power Field)	Baseline to Day 85
Secondary	Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period	In subjects with baseline hematuria >=30 RBCs/hpf,(Red Blood Cell/High Power Field)	Baseline to Day 85
Secondary	Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period	In subjects with baseline hematuria <=30 RBCs/hpf (Red Blood Cell/High Power Field)	Baseline to Day 85
Secondary	Percent Change From Baseline to Day 85 in Urinary RBC Count	In subjects with hematuria at baseline, RBC (Red Blood Cell)	Baseline to day 85
Secondary	Percent Change From Baseline to Day 85 in UACR	In subjects with albuminuria at baseline UACR (urinary albumin:creatinine ratio)	Baseline to Day 85
Secondary	Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio	Urinary Monocyte Chemoattractant Protein-1 (MCP-1):creatinine ratio	Baseline to Day 85
Secondary	Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment		Baseline to Day 85
Secondary	Change From Baseline to Day 85 in the Vasculitis Damage Index	VDI=Vasculitis Damage Index; The VDI is comprised of 64 items of damage, grouped into 11 organ-based systems or categorizations. Damage is defined as the presence of non-healing scars and does not give any indication of current disease activity. Damage is also defined as having been present or currently present for at least 3 months. Completion of the form provides a numerical score, which ranges from 0 (best health) to 64 (worst health).	Baseline to Day 85
Secondary	Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the SF-36 v2	SF-36v2: Medical Outcomes Survey Short Form-36 version 2. SF-36v2 measures each of the following eight health domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Scores on each item are summed and averaged. The SF-36v2 component domain scores range from 0 (worst health) to 100 (best health).	Baseline, Day 29 & Day 85
Secondary	Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L	EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels. The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The answers given can be converted into an Index Score ranging from 0 for death to 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst imaginable health) to 100 (the best imaginable health).	Baseline, Day 29 and Day 85

External Links

•   Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis