We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Controlled Trial Evaluating Avacopan in C3 Glomerulopathy (ACCOLADE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03301467
Recruitment Status : Completed
First Posted : October 4, 2017
Results First Posted : October 14, 2022
Last Update Posted : October 14, 2022
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
ChemoCentryx

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The aim of this trial is to evaluate the effect of avacopan treatment on renal disease activity in patients with complement component 3 glomerulopathy (C3G). Funding Source - FDA OOPD

Condition or disease Intervention/treatment Phase
C3 Glomerulopathy (C3G) Drug: Avacopan Drug: Avacopan Matching Placebo Phase 2

Detailed Description:

C3 glomerulopathy (C3G) is characterized by evidence of alternative complement activation based on C3 deposition in the glomeruli. There are two forms of the disease: dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). There is no approved treatment for patients with C3G.

This is a randomized, double blind, placebo controlled Phase 2 study to evaluate the safety and efficacy of avacopan (CCX168) in patients with C3G. Patients receive avacopan 30mg or matching placebo orally twice-daily. The placebo-controlled treatment period is 26 weeks (182 days). This will be followed by 26 weeks during which time all patients will receive avacopan (results for this second period will be reported in due course in a follow-up publication). Thereafter, all patients will be followed for eight weeks (56 days) without study drug treatment. The primary objective is to evaluate the efficacy of avacopan compared to placebo based on histologic changes in kidney biopsies taken at baseline and after 26 weeks of treatment. The primary endpoint will be based on the percent change from baseline in the C3G Histologic Index for disease activity.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Placebo crossover to active
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Matching placebo
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Avacopan (CCX168) in Patients With C3 Glomerulopathy
Actual Study Start Date : September 29, 2017
Actual Primary Completion Date : March 3, 2021
Actual Study Completion Date : October 27, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Avacopan

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Avacopan
Avacopan (formerly CCX168) 10 mg capsules x 3 administered twice daily during the blinded 26 week blinded treatment period
 Drug: Avacopan
Orally administered
Other Name: CCX168
Placebo Comparator: Avacopan Matching Placebo
Matching placebo capsules x 3 administered twice daily during the 26 week blinded treatment period period
 Drug: Avacopan Matching Placebo
avacopan matching placebo
Other Name: placebo


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]

    Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease activity - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

    C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement.

    C3G=C3 glomerulopathy


  2. Percent Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Combined C5b-9 Strata [ Time Frame: Week 26 ]

    Percent change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease activity - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

    C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement.

    C3G=C3 glomerulopathy

    * Multiple Imputation: Missing Week 26 values are imputed using the regression method to create 100 complete datasets.



Secondary Outcome Measures :
  1. Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]

    Proportion of subjects who have a histologic response defined as a decrease (improvement) in the biopsy-based C3G Histologic Index for activity of at least 35% from baseline to 26 weeks - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

    C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement.

    C3G=C3 glomerulopathy


  2. Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Combined C5b-9 Strata [ Time Frame: Week 26 ]

    Proportion of subjects who have a histologic response defined as a decrease (improvement) in the biopsy-based C3G Histologic Index for activity of at least 35% from baseline to 26 weeks - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

    C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement.

    C3G=C3 glomerulopathy


  3. Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]

    Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease chronicity over the placebo-controlled treatment period - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

    C3G Histological Index for Disease Chronicity Scores can range from 0 to 10. A decrease indicates improvement.

    C3G=C3 glomerulopathy


  4. Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata [ Time Frame: Week 26 ]

    Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease chronicity over the placebo-controlled treatment period - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

    C3G Histological Index for Disease Chronicity Scores can range from 0 to 10. A decrease indicates improvement.

    C3G=C3 glomerulopathy


  5. Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]
    The percent change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

  6. Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata [ Time Frame: Week 26 ]
    The percent change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

  7. Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]
    The change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

  8. Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata [ Time Frame: Week 26 ]
    The change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

  9. Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]

    Percent change from baseline Over 26 Weeks in UPCR in patients with Abnormal UPCR at Baseline (>= 0.15 g/g) - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

    LSM=Least Squares Mean; UPCR = Urine Protein : Creatinine Ratio


  10. Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Combined C5b-9 Strata [ Time Frame: Week 26 ]

    Percent change from baseline Over 26 Weeks in UPCR in patients with Abnormal UPCR at Baseline (>= 0.15 g/g) - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

    LSM=Least Squares Mean; UPCR = Urine Protein : Creatinine Ratio


  11. Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]

    Percent change from baseline over 26 weeks in urinary MCP-1: creatinine ratio - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

    LSM=Least Squares Mean; MCP-1=Monocyte Chemoattractant Protein-1


  12. Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Combined C5b-9 Strata [ Time Frame: Week 26 ]

    Percent change from baseline over 26 weeks in urinary MCP-1: creatinine ratio - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

    LSM=Least Squares Mean; MCP-1=Monocyte Chemoattractant Protein-1


  13. Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]

    Change from baseline over 26 weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

    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).


  14. Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata [ Time Frame: Week 26 ]

    Change from baseline over 26 weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

    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).


  15. Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 [ Time Frame: Week 26 ]

    Change from baseline over 26 weeks in SF-36 v2 - Subjects with Elevated C5b-9 (> 244 ng/mL) in the Intent-to-Treat Population.

    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).


  16. Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata [ Time Frame: Week 26 ]

    Change from baseline over 26 weeks in SF-36 v2 - Combined C5b-9 Strata (elevated [> 244 ng/mL] and non-elevated C5b-9) in the Intent-to-Treat Population.

    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).


  17. Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs [ Time Frame: From day 1 throughout the study period (day 182/week 26) ]

    Number of Subjects with Treatment-emergent SAEs, AEs, relatedness to study medication and Withdrawals Due to AEs

    AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse events 'Possibly related' refers to the Investigators' causality assessment


  18. Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs [ Time Frame: From day 1 throughout the study period (day 182/week 26) ]

    Number of Treatment-emergent SAEs, AEs, relatedness to study medication and Withdrawals Due to AEs

    AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse events 'Possibly related' refers to the Investigators' causality assessment



Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Biopsy-proven C3G, either DDD or C3GN, with or without a renal transplant, and with the following observations upon renal biopsy taken within 12 weeks prior to screening or during screening:

    1. ≥2-levels of magnitude greater staining of C3 than any combination of IgG, IgM, IgA, kappa and lambda light chains, and C1q by immunohistochemistry, and
    2. evidence of proliferative glomerulonephritis (mesangial hypercellularity of greater than 3 mesangial cells per mesangial area and/or endocapillary hypercellularity defined as an increased number of cells within glomerular capillary lumina, causing luminal narrowing) based on light microscopy, and
    3. confirmation of the presence of electron dense deposits in the glomeruli on electron microscopy corresponding with the C3 immunofluorescence positivity;
  2. Male or female subjects, aged at least 18 years; where approved, adolescents (12-17 year old) may be enrolled; female subjects of childbearing potential (i.e., those who have experienced menarche and who is not permanently sterile or postmenopausal, defined as at least 12 consecutive months with no menses without an alternative medical cause) may participate if adequate contraception is used during, and for at least the three months after study completion; Male subjects with partners of childbearing potential may participate in the study if they had a vasectomy at least 6 months prior to randomization or if adequate contraception is used during, and for at least the 3 months after study completion; Adequate contraception is defined as resulting in a failure rate of less than 1% per year (combined estrogen and progestogen [oral, intravaginal, or transdermal], or progestogen-only hormonal contraception (oral, injectable, or implantable), intra-uterine device, intra-uterine hormone releasing system, bilateral tubal occlusion, vasectomized partner, or true sexual abstinence, i.e., in line with the preferred and usual lifestyle of the subject);
  3. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; written Assent and Informed Consent must be obtained from the legal guardian in accordance with regional laws or regulations for subjects 12 to 17 years of age; and
  4. Judged to be otherwise fit for the study by the Investigator, based on medical history, physical examination, and clinical laboratory assessments. Subjects with clinical laboratory values that are outside of normal limits (other than those specified in the Exclusion Criteria) and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance, may be entered into the study.

Exclusion Criteria:

  1. Pregnant or nursing;
  2. Tubulointerstitial fibrosis appears to be more than 50% based on standard assessment using trichrome staining of the renal biopsy;
  3. Use of eculizumab or another anti-C5 antibody within 26 weeks prior to dosing;
  4. Secondary C3 disease, e.g., infection-associated disease, or associated with another systemic or autoimmune disease; presence of a monoclonal spike on serum or urine protein electrophoresis or immunofixation assay;
  5. Currently on dialysis or likely will require dialysis within 7 days after screening;
  6. History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis;
  7. Positive hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) viral screening test indicative of acute or chronic infection;
  8. Evidence of tuberculosis based on interferon γ release assay (IGRA), tuberculin purified protein derivative (PPD) skin test, or chest radiography done at screening or within 6 weeks prior to screening;
  9. WBC count less than 3500/μL, or neutrophil count less than 1500/μL, or lymphocyte count less than 500/μL before start of dosing;
  10. Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin >3 x the upper limit of normal before start of dosing;
  11. Currently using a strong inducer of the CYP3A4 enzyme, such as carbamazepine, phenobarbital, phenytoin, rifampin, or St. John's wort;
  12. Known hypersensitivity to avacopan or inactive ingredients of the avacopan capsules (including gelatin, polyethylene glycol, or Cremophor) or inability to swallow the capsules;
  13. Participated in any clinical study of an investigational product within 30 days prior to screening or within 5 half-lives after taking the last dose; and
  14. History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03301467


Locations
Layout table for location information
United States, California
Clinical Site
Palo Alto, California, United States, 94305
United States, Illinois
Clinical Site
Chicago, Illinois, United States, 60611
United States, Iowa
Clinical Site
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Clinical Site
Boston, Massachusetts, United States, 02114
United States, New York
Clinical Site
New York, New York, United States, 10032
Clinical Site
Rochester, New York, United States, 14625
United States, Ohio
Clinical Site
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Clinical Site
Philadelphia, Pennsylvania, United States, 19107
United States, Rhode Island
Clinical Trial Site
East Providence, Rhode Island, United States, 02914
Belgium
Clinical Site
Antwerp, Belgium
Clinical Site
Brussels, Belgium
Clinical Site
Leuven, Belgium
Clinical Site
Liège, Belgium
Canada, British Columbia
Clinical Site
Vancouver, British Columbia, Canada
Canada
Clinical Site
Calgary, Canada
Denmark
Clinical Site
Aalborg, Denmark
Clinical Site
Copenhagen, Denmark
Clinical Site
Odense, Denmark
France
Clinical Site
Boulogne-sur-Mer, France
Clinical Site
Grenoble, France
Clinical Site
Paris, France
Clinical Site
Valenciennes, France
Germany
Clinical Site
Dresden, Germany
Clinical Site
Essen, Germany
Clinical Site
Hannover, Germany
Clinical Site
Lübeck, Germany
Clinical Site
Munich, Germany
Ireland
Clinical Site
Dublin, Ireland
Italy
Clinical Site
Bergamo, Italy
Clinical Site
Bologna, Italy
Clinical Site
Milano, Italy
Clinical Site
Parma, Italy
Clinical Site
Roma, Italy
Netherlands
Clinical Site
Amsterdam, Netherlands
Clinical Site
Leiden, Netherlands
Clinical Site
Nijmegen, Netherlands
Spain
Clinical Site
Barcelona, Spain
Clinical Site
Burela De Cabo, Spain
Clinical Site
Madrid, Spain
United Kingdom
Clinical Site
London, United Kingdom
Clinical Site
Newcastle Upon Tyne, United Kingdom
Sponsors and Collaborators
ChemoCentryx
Medpace, Inc.
  Study Documents (Full-Text)

Documents provided by ChemoCentryx:
Study Protocol  [PDF] March 20, 2019
Statistical Analysis Plan  [PDF] November 5, 2020

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: ChemoCentryx
ClinicalTrials.gov Identifier: NCT03301467    
Other Study ID Numbers: CL011_168
1R01FD006342-01 ( U.S. FDA Grant/Contract )
First Posted: October 4, 2017    Key Record Dates
Results First Posted: October 14, 2022
Last Update Posted: October 14, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ChemoCentryx:
C3 Glomerulonephritis
C3 glomerulopathy
C3G
DDD
dense deposit disease
 membranoproliferative glomerulonephritis
MPGN
C3GN
idiopathic MPGN