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Controlled Trial Evaluating Avacopan in C3 Glomerulopathy

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ClinicalTrials.gov Identifier: NCT03301467
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : June 18, 2019
Sponsor:
Information provided by (Responsible Party):
ChemoCentryx

Tracking Information
First Submitted Date  ICMJE September 22, 2017
First Posted Date  ICMJE October 4, 2017
Last Update Posted Date June 18, 2019
Actual Study Start Date  ICMJE September 29, 2017
Estimated Primary Completion Date December 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2017)
Histologic Index [ Time Frame: 26 weeks ]
Percent change from baseline in the C3G Histologic Index for disease activity
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03301467 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2017)
  • Histologic response [ Time Frame: 26 weeks ]
    The proportion of subjects who have a histologic response defined as a decrease (improvement) in the C3G Histologic Index for activity at 26 weeks
  • Histologic Index [ Time Frame: 26 weeks ]
    The percent change from baseline in the C3G Histologic Index for disease chronicity over the placebo-controlled treatment period
  • eGFR [ Time Frame: 26 weeks ]
    The change from baseline in eGFR over the placebo-controlled treatment period
  • eGFR [ Time Frame: 26 weeks ]
    The percent change from baseline in eGFR over the placebo-controlled treatment period
  • UPCR [ Time Frame: 26 weeks ]
    The percent change from baseline in UPCR over the placebo-controlled treatment period
  • Urinary MCP-1 [ Time Frame: 26 weeks ]
    The percent change from baseline in urinary MCP-1: creatinine ratio over the placebo-controlled treatment period
  • EQ-5D-5L [ Time Frame: 26 weeks ]
    Change from baseline in EQ-5D-5L (visual analogue scale and index) over the placebo-controlled treatment period
  • SF-36 v2 [ Time Frame: 26 weeks ]
    Change from baseline in SF-36 v2(domains and component scores) over the placebo-controlled treatment period
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Controlled Trial Evaluating Avacopan in C3 Glomerulopathy
Official Title  ICMJE A Randomized, Double Blind, Placebo Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Avacopan (CCX168) in Patients With C3 Glomerulopathy
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).
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. The primary objective is to evaluate the efficacy of avacopan compared to placebo based on histologic changes in kidney biopsies taken before and during treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE C3 Glomerulopathy (C3G)
Intervention  ICMJE
  • Drug: Avacopan
    Orally administered
    Other Name: CCX168
  • Drug: Avacopan Matching Placebo
    avacopan matching placebo
    Other Name: placebo
Study Arms  ICMJE
  • Experimental: Avacopan
    Avacopan (formerly CCX168) 10 mg capsules x 3 administered twice daily during the blinded 26 week blinded treatment period
    Intervention: Drug: Avacopan
  • Placebo Comparator: Avacopan Matching Placebo
    Matching placebo capsules x 3 administered twice daily during the 26 week blinded treatment period period
    Intervention: Drug: Avacopan Matching Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2018)
88
Original Estimated Enrollment  ICMJE
 (submitted: September 29, 2017)
44
Estimated Study Completion Date  ICMJE December 30, 2020
Estimated Primary Completion Date December 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antonia Potarca +31 6 3089 2290 C3Gtrial@chemocentryx.com
Contact: Peter Staehr C3Gtrial@chemocentryx.com
Listed Location Countries  ICMJE Belgium,   Canada,   Denmark,   France,   Germany,   Ireland,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03301467
Other Study ID Numbers  ICMJE CL011_168
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party ChemoCentryx
Study Sponsor  ICMJE ChemoCentryx
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Peter Staehr, MD ChemoCentryx, Inc.
PRS Account ChemoCentryx
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP