Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis

NCT02222155 | Completed Phase 2 Results DMC

• 2 other identifiers: CL003_168#FD-R-5414
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 43

Brief Summary

The aim of this trial is to test the safety and efficacy of two dose regimens of the complement C5a receptor CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Funding Source - FDA OOPD

Conditions

ANCA-associated Vasculitis

Keywords

ANCA-associated vasculitis; complement; vasculitis; C5aR

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events

  This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms.

  Baseline to Day 85

• Proportion of Patients Achieving Disease Response Based on BVAS at Day 85

  Proportion of Patients achieving 50% reduction in the Birmingham Vasculitis Activity Score \[BVAS\] at Day 85 and no worsening in any body system component at day 85

  Day 85

Secondary Outcomes (13)

• Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85.

  Day 85

• Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85.

  Day 29 and 85

• Percent Change From Baseline to Day 85 in BVAS.

  Baseline to Day 85

• Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85

  Day 85

• Change in Estimated Glomerular Filtration Rate at Day 85

  Baseline to Day 85

Study Arms (3)

CCX168 low dose plus standard of care

ACTIVE COMPARATOR

Capsule, 10 mg, twice daily + standard of care for 12 weeks

Drug: CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids

CCX168 high dose plus standard of care

ACTIVE COMPARATOR

Capsule, 30 mg, twice daily + standard of care for 12 weeks

Drug: CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids

Placebo, twice daily + standard of care

PLACEBO COMPARATOR

Capsule, placebo, twice daily + standard of care for 12 weeks

Other: Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids

Interventions

CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids DRUG

CCX168 low dose plus standard of care

CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids DRUG

CCX168 high dose plus standard of care

Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids OTHER

Placebo, twice daily + standard of care

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 female subjects, aged at least 18 years, with new or relapsed AAV where treatment with cyclophosphamide or rituximab would be required
• Use of adequate contraception during, and for at least the three months after, any administration of study medication is 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
• Have at least one "major" item, or at least 3 other items, or at least 2 renal items on the Birmingham Vasculitis Activity Score (BVAS) version 3
• Estimated glomerular filtration rate (eGFR) ≥ 20 mL per minute

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 prior to 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 intravenous corticosteroids, \>3000 mg methylprednisolone equivalent, within 12 weeks prior to screening
• Received an oral daily dose of a corticosteroid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to the screening visit
• Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred; received anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg), belimumab, tocilizumab, or plasma exchange within 12 weeks prior to screening

Sponsors & Collaborators

• Amgen: lead

Study Sites (43)

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Huntsville, Alabama, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Miami Springs, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Kansas City, Kansas, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Shreveport, Louisiana, United States

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Charlestown, Massachusetts, United States

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Duluth, Minnesota, United States

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Tupelo, Mississippi, United States

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St Louis, Missouri, United States

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Reno, Nevada, United States

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Lebanon, New Hampshire, United States

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Albuquerque, New Mexico, United States

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Great Neck, New York, United States

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Mineola, New York, United States

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New York, New York, United States

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Syracuse, New York, United States

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Chapel Hill, North Carolina, United States

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New Bern, North Carolina, United States

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Columbus, Ohio, United States

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Duncansville, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Providence, Rhode Island, United States

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Charleston, South Carolina, United States

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Chattanooga, Tennessee, United States

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Amarillo, Texas, United States

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Austin, Texas, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Calgary, Alberta, Canada

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Toronto, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Lévis, Quebec, Canada

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Related Publications (1)

• Merkel PA, Niles J, Jimenez R, Spiera RF, Rovin BH, Bomback A, Pagnoux C, Potarca A, Schall TJ, Bekker P; CLASSIC Investigators. Adjunctive Treatment With Avacopan, an Oral C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. ACR Open Rheumatol. 2020 Nov;2(11):662-671. doi: 10.1002/acr2.11185. Epub 2020 Oct 31.

  PMID: 33128347 DERIVED

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Vasculitis

Interventions

avacopan; Rituximab; Glucocorticoids; Cyclophosphamide

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

The study had a small sample size and was not powered to detect differences between avacopan or placebo arms or among subgroups of patients such as newly-diagnosed vs. relapsed status, or on the basis of characteristics such as ANCA type.

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
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 21, 2014
• Study Start: February 4, 2015
• Primary Completion: April 24, 2016
• Study Completion: July 19, 2016
• Last Updated: March 13, 2025
• Results First Posted: August 16, 2023

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

US (39); CA (4)