Study to evaluate the safety and efficacy of CCX168 in subjects with renal vasculitis on background cyclophosphamide treatment
| ISRCTN | ISRCTN53663626 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN53663626 |
| ClinicalTrials.gov number | NCT01363388 |
| Secondary identifying numbers | CL002_168 |
- Submission date
- 09/07/2011
- Registration date
- 25/08/2011
- Last edited
- 21/01/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
ANCA-associated renal vasculitis (AARV) is an autoimmune disease involving multiple organs including the kidneys. It is caused by abnormal antibodies (autoantibodies) that attack a certain type of white blood cells (neutrophils) and can cause those neutrophils to stick to and destroy the inside walls of small blood vessels in tissue and organs such as the kidney. ANCA is an acronym for Anti-Neutrophil Cytoplasmic Antibody.
The aim of this study is to test a newly developed drug (oral investigational product CCX168) for safety and tolerability while you continue to receive the standard of care cyclophosphamide treatment, and varying doses of prednisone or prednisone placebo.
Who can participate?
Patients aged 18-75 who are experiencing a recent relapse or new diagnosis of ANCA-associated renal vasculitis.
What does the study involve?
Some patients will receive capsules of CCX168 or placebo, and capsules of prednisone or prednisone-placebo daily for a period of 84 days. This is in addition to their standard of care intravenous cyclophosphamide treatment.
What are the possible benefits and risks of participating?
If successful, CCX168 could possibly allow for lower dosing or complete elimination of high dose corticosteroid treatment in this disease. As a result patients with this disease may have less of the toxic side effects usually caused by high dose corticosteroids. CCX168 appeared to be well tolerated in Phase I studies with healthy subjects and adverse events were mild in nature. All new drugs (investigational compounds) have the potential for unanticipated serious or life-adverse events. These side effects could be in addition to the well documented side effects of cyclophosphamide and high dose corticosteroid standard of care treatments.
Where is the study run from?
There are about 40 sites participating in this study. They are located in Belgium, Czech Republic, Germany, Hungary, the Netherlands, Poland, Sweden and the UK. The lead study center is at Addenbrookes Hospital, Department of Nephrology at Cambridge in the UK.
When is the study starting and how long is it expected to run for?
Patient screening and dosing are scheduled to begin in the fall of 2011 completing in December 2012.
Who is funding the study?
ChemoCentryx (USA)
Who is the main contact?
Antonia Potarca
apotarca@chemocentryx.com
Contact information
Scientific
Addenbrooke's Hospital
Hills Road
Department of Nephrology
Cambridge
CB2 0QQ
United Kingdom
| Dj106@cam.ac.uk |
Study information
| Study design | Multi-centre randomized double-blind placebo-controlled phase 2 study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A randomized, double-blind, placebo-controlled, phase 2 study to evaluate the safety and efficacy of CCX168 in subjects with renal vasculitis on background cyclophosphamide treatment |
| Study acronym | CLEAR (C5aR inhibitor on Leukocytes Exploratory ANCA-associated Renal vasculitis study) |
| Study objectives | That CCX168, a C5a complement receptor, will be safe, well tolerated and effective in patients with antineutrophil cytoplasmic antibodies ANCA-associated renal vasculitis on background cyclophosphamide treatment and may result in reduced toxicity of induction therapy by the reduction of or the elimination of systemic corticosteroid therapy. |
| Ethics approval(s) | NRES Committee East of England-Cambridge Central, 13/10/2011, ref: 11/EE/0210 All other centres will seek ethics approval before recruitment of the first participant |
| Health condition(s) or problem(s) studied | Renal Vasculitis |
| Intervention | 1. Treatment: CCX168 30mg or placebo twice daily for 84 days 2. Comparator: Prednisone at starting doses ranging from 15 to 60 mg (body weight dependent) per day for 84 days or matching prednisone placebo once daily for 84 days |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | CCX168, prednisone, cyclophosphamide |
| Primary outcome measure | Safety of CCX168 in patients with anti-neutrophil cytoplasmic antibody associated renal vasculitis measured upon completion of 84 days of treatment. |
| Secondary outcome measures | Systemic corticosteroid use measured upon completion of 84 days of treatment. |
| Overall study start date | 01/08/2011 |
| Completion date | 31/03/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 75 Years |
| Sex | Both |
| Target number of participants | Approximately 60 |
| Key inclusion criteria | 1. Clinical diagnosis of Wegeners granulomatosis, microscopic polyangiitis or renal limited vasculitis 2. Male and postmenopausal or surgically sterile female subjects, aged 18-75 years with new or relapsed ANCA-associated renal vasculitis (AARV) where treatment with cyclophosphamide would be required 3. Positive indirect immunofluorescence (IIF) test for peri-nuclear (protoplasmic-staining) antineutrophil cytoplasmic antibodies (P-ANCA) or C-ANCA, or positive Enzyme-linked immunosorbent assay (ELISA) test for anti-proteinase-3 (PR3) or anti-myeloperoxidase (MPO) at screening 4. Proven to have renal vasculitis based on renal biopsy or have hematuria and proteinuria compatible with nephritis 5. Estimated glomerular filtration rate of greater than 30 mL per minute |
| Key exclusion criteria | 1. Severe disease as determined by rapidly progressive glomerulonephritis, alveolar hemorrhage, hemoptysis, rapid-onset mononeuritis multiplex or central nervous system involvement 2. Any other multi-system autoimmune disease 3. Medical history of coagulopathy or bleeding disorder 4. 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 dose on Day 1 5. Received high-dose intravenous corticosteroids within 4 weeks of screening 6. On an oral dose of a corticosteroid of more than 10 mg prednisone-equivalent at the time of screening 7. 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, intravenous immunoglobulin (IVIg), or plasma exchange within 12 weeks of screening |
| Date of first enrolment | 01/08/2011 |
| Date of final enrolment | 31/03/2013 |
Locations
Countries of recruitment
- Belgium
- Czech Republic
- England
- Germany
- Hungary
- Netherlands
- Poland
- Sweden
- United Kingdom
Study participating centre
CB2 0QQ
United Kingdom
Sponsor information
Industry
850 Maude Avenue
Mountain View
California
94043
United States of America
"ROR" |
https://ror.org/04gp12571 |
|---|
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | To be confirmed at a later date |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/09/2017 | 21/01/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
21/01/2019: Publication reference added
01/03/2016: No publications found, verifying study status with principal investigator
