CL002_168 ANCA-Associated Renal Vasculitis

• Research type

  Research Study

• Full title

  A 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 Renal Vasculitis on Background Cyclophosphamide Treatment

• IRAS ID

  78485

• Contact name

  David Jayne

• Eudract number

  2011-001222-15

• ISRCTN Number

  NA

• Clinicaltrials.gov Identifier

  NA

• Research summary

  AARV standard therapy includes cyclophosphamide (IV or oral, although IV is preferred because of a lower cumulative dose and lower toxicity), and oral corticosteroids, tapered over a period of time. Severe disease warrants addition of IV corticosteroids and/or plasma exchange. Results from recent clinical trials (Jones et al. 2010 and Stone et al. 2010) that have attempted to eliminate cyclophosphamide use, indicated that the incidence of adverse events and the mortality rate remain high. High dose corticosteroid use likely contributes significantly to this high morbidity and mortality rates. Therefore, the medical need for alternative therapies remains high and it is important to find ways to reduce or eliminate corticosteroid use in the treatment of AARV. Based on encouraging results from preclinical studies in a human C5aR knock-in mouse model of AARV, CCX168 has the potential to be a corticosteroid sparing or corticosteroid replacement therapy for this disease, with potential safety and tolerability advantages. Hence, the clinical hypothesis of the trial is to test the feasibility of using CCX168 as a corticosteroid sparing or replacement therapy during the period of induction of remission of AARV. Results from a Phase 1 clinical trial conducted in human volunteers indicated that CCX168 was well tolerated with a pharmacokinetic profile lending it to twice daily oral dosing, in order to provide sufficient C5aR coverage. Therefore, the rationale for this Phase 2 study is to determine whether CCX168 is safe and well tolerated and shows evidence of efficacy, based on its potential to be corticosteroid-sparing, after oral administration of CCX168 for 84 consecutive days to subjects with AARV.

• REC name

  East of England - Cambridge Central Research Ethics Committee

• REC reference

  11/EE/0210

• Date of REC Opinion

  13 Oct 2011

• REC opinion

  Further Information Favourable Opinion