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

NCT01363388 | Completed Phase 2 Results DMC

• 1 other identifier: CL002_168
• Study Type: interventional
• Target: 67
• Locations: 10 countries
• Sites: 44

Brief 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.

Conditions

Vasculitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Proportion of Patients Achieving Renal Response at Day 85

  Baseline to Day 85

• Proportion of Subjects Achieving Disease Remission at Day 85

  Day 85

• Percent Change From Baseline to Day 85 in BVAS

  Baseline to Day 85

• Change From Baseline to Day 85 in eGFR

  Baseline to Day 85

• Percent Change From Baseline to Day 85 in eGFR

  Baseline to Day 85

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo plus a full dose of oral glucocorticoids for steps 1 and 2 of the study

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

Drug: CCX168

Interventions

Placebo DRUG

BID for 84 days

Placebo

CCX168 DRUG

BID for 84 days

CCX168

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (44)

Unknown Facility

Feldkirch, Austria

Location

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Innsbruck, Austria

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Linz, Austria

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Brussels, Belgium

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Edegem, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Liège, Belgium

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Roeselare, Belgium

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Prague, Czechia

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Bordeaux, France

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Boulogne-sur-Mer, France

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Brest, France

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Colmar, France

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Grenoble, France

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Nantes, France

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Paris, France

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Saint-Jacques, France

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Valenciennes, France

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Berlin, Germany

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Cologne, Germany

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Dresden, Germany

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Freiburg im Breisgau, Germany

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Fulda, Germany

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Heidelberg, Germany

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Budapest, Hungary

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Groningen, Netherlands

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Leiden, Netherlands

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Rotterdam, Netherlands

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Utrecht, Netherlands

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Bialystok, Poland

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Katowice, Poland

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Szczecin, Poland

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Wroclaw, Poland

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Linköping, Sweden

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Lund, Sweden

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Malmo, Sweden

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Stockholm, Sweden

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Birmingham, United Kingdom

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Cambridge, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Oxford, United Kingdom

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Reading, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24033923 DERIVED

Related Links

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

MeSH Terms

Conditions

Vasculitis

Interventions

avacopan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

This study is relatively small and the treatment duration was short.

Results Point of Contact

• Title: Study Director
• Organization: ChemoCentryx

650-210-2900

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2011
• First Posted: June 1, 2011
• Study Start: September 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: January 1, 2016
• Last Updated: March 13, 2025
• Results First Posted: July 27, 2020

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

HU (1); GB (6); CZ (1); PL (4); BE (6); NL (4); FR (9); SE (4); AU (3); DE (6)