VasculitisPhase 2NCT01363388
A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis
A Phase 2 study testing CCX168 in people with Vasculitis, run by Amgen at 44 sites in 10 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vasculitis
- What is being tested?
- CCX168
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 44 sitesin 10 countries
- Study dates
- Sep 2011to Jan 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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of screening; if on azathioprine, mycophenolate mofetil or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1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
Trial locations and contacts
44 sites in 10 countries.
44 sites in 10 countries
France9 sites
Study site
Bordeaux
Study site
Boulogne-sur-Mer
Study site
Brest
Study site
Colmar
Study site
Grenoble
Study site
Nantes
Study site
Paris
Study site
Saint-Jacques
Study site
Valenciennes
Belgium6 sites
Study site
Brussels
Study site
Edegem
Study site
Ghent
Study site
Leuven
Study site
Liège
Study site
Roeselare
Germany6 sites
Study site
Berlin
Study site
Cologne
Study site
Dresden
Study site
Freiburg im Breisgau
Study site
Fulda
Study site
Heidelberg
United Kingdom6 sites
Study site
Birmingham
Study site
Cambridge
Study site
London
Study site
Manchester
Study site
Oxford
Study site
Reading
Netherlands4 sites
Study site
Groningen
Study site
Leiden
Study site
Rotterdam
Study site
Utrecht
Poland4 sites
Study site
Bialystok
Study site
Katowice
Study site
Szczecin
Study site
Wroclaw
Sweden4 sites
Study site
Linköping
Study site
Lund
Study site
Malmö
Study site
Stockholm
About this study
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
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.
Read the detailed 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.
Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.
- Conditions
- Vasculitis
- Being tested
- Placebo, CCX168
- Medical subject headings
- Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
BID for 84 days
CCX168Drug
BID for 84 days
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo plus a full dose of oral glucocorticoids for steps 1 and 2 of the study Receives: Drug: Placebo |
| CCX168 | Experimental | 30 mg Active study medication, plus either two-thirds reduced dose of oral glucocorticoids for step 1 of the study, or no oral glucocorticoids for step 2 of the study Receives: Drug: CCX168 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Day 85
Secondary outcomes (16)
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).
Measured: Baseline to Day 85
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)
Measured: Day 85
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.
Measured: Baseline to Day 85
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
Measured: Baseline to Day 85
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
Measured: Baseline to Day 85
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)
Measured: Baseline to Day 85
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)
Measured: Baseline to Day 85
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)
Measured: Baseline to Day 85
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)
Measured: Baseline to Day 85
Percent Change From Baseline to Day 85 in Urinary RBC Count
In subjects with hematuria at baseline, RBC (Red Blood Cell)
Measured: Baseline to day 85
Percent Change From Baseline to Day 85 in UACR
In subjects with albuminuria at baseline UACR (urinary albumin:creatinine ratio)
Measured: Baseline to Day 85
Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio
Urinary Monocyte Chemoattractant Protein-1 (MCP-1):creatinine ratio
Measured: Baseline to Day 85
Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment
Measured: Baseline to Day 85
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).
Measured: Baseline to Day 85
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).
Measured: Baseline, Day 29 & Day 85
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).
Measured: Baseline, Day 29 and Day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2011 (estimated)
- Study startSep 2011
- Primary completionOct 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for VasculitisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01363388
- Sponsor's protocol ID
- CL002_168
- Status last verified
- Mar 2025
- First submitted
- 26 May 2011
- Last updated
- 13 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Publications
Cravedi P, Leventhal J, Lakhani P, Ward SC, Donovan MJ, Heeger PS. Immune cell-derived C3a and C5a costimulate human T cell alloimmunity. Am J Transplant. 2013 Oct;13(10):2530-9. doi: 10.1111/ajt.12405. Epub 2013 Sep 6.
PubMed 24033923
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01363388
- Acronym / sponsor ID
- CL002_168
- Conditions
- Vasculitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Oct 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 1 Jun 2011 (estimated)
- Results
- Posted 27 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo plus a full dose of oral glucocorticoids for steps 1 and 2 of the study |
| CCX168 | Experimental | Drug: CCX16830 mg Active study medication, plus either two-thirds reduced dose of oral glucocorticoids for step 1 of the study, or no oral glucocorticoids for step 2 of the study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboBID for 84 days | Drug | Placebo |
| CCX168BID for 84 days | Drug | CCX168 |
Primary outcome
Proportion of Subjects Achieving Disease Response at Day 85
Time frame: Baseline to Day 85
Disease response is defined as BVAS percentage reduction from baseline of at least 50% plus no worsening in any body system component.
16 secondary outcomes
Proportion of Patients Achieving Renal Response at Day 85
Time frame: Baseline to Day 85
Proportion of Subjects Achieving Disease Remission at Day 85
Time frame: Day 85
Percent Change From Baseline to Day 85 in BVAS
Time frame: Baseline to Day 85
Change From Baseline to Day 85 in eGFR
Time frame: Baseline to Day 85
Percent Change From Baseline to Day 85 in eGFR
Time frame: Baseline to Day 85
Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period
Time frame: Baseline to Day 85
Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period
Time frame: Baseline to Day 85
Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period
Time frame: Baseline to Day 85
Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period
Time frame: Baseline to Day 85
Percent Change From Baseline to Day 85 in Urinary RBC Count
Time frame: Baseline to day 85
Percent Change From Baseline to Day 85 in UACR
Time frame: Baseline to Day 85
Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio
Time frame: Baseline to Day 85
Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment
Time frame: Baseline to Day 85
Change From Baseline to Day 85 in the Vasculitis Damage Index
Time frame: Baseline to Day 85
Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the SF-36 v2
Time frame: Baseline, Day 29 & Day 85
Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L
Time frame: Baseline, Day 29 and Day 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24033923Cravedi P, Leventhal J, Lakhani P, Ward SC, Donovan MJ, Heeger PS. Immune cell-derived C3a and C5a costimulate human T cell alloimmunity. Am J Transplant. 2013 Oct;13(10):2530-9. doi: 10.1111/ajt.12405. Epub 2013 Sep 6.
- Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated VasculitisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
44 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CCX168 in people with Vasculitis, run by Amgen at 44 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in France, Belgium, Germany, United Kingdom, Netherlands and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Subjects Achieving Disease Response at Day 85 (time frame: Baseline to Day 85). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01363388, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.