Controlled Trial Evaluating Avacopan in C3 Glomerulopathy

NCT03301467 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CL011_1681R01FD006342-01
• Study Type: interventional
• Target: 57
• Locations: 11 countries
• Sites: 45

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

Conditions

C3 Glomerulopathy (C3G)

Keywords

C3 Glomerulonephritis; C3 glomerulopathy; C3G; DDD; dense deposit disease; membranoproliferative glomerulonephritis; MPGN; C3GN; idiopathic MPGN

Outcome Measures

Primary Outcomes (2)

• Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Subjects With Elevated C5b-9

  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

  Week 26

• Percent Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Combined C5b-9 Strata

  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.

  Week 26

Secondary Outcomes (18)

• 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

  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

  Week 26

• Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Subjects With Elevated C5b-9

  Week 26

• Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata

  Week 26

• Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9

  Week 26

Study Arms (2)

Avacopan

EXPERIMENTAL

Avacopan (formerly CCX168) 10 mg capsules x 3 administered twice daily during the blinded 26 week blinded treatment period

Drug: Avacopan

Avacopan Matching Placebo

PLACEBO COMPARATOR

Matching placebo capsules x 3 administered twice daily during the 26 week blinded treatment period period

Drug: Avacopan Matching Placebo

Interventions

Avacopan DRUG

Orally administered

Also known as: CCX168

Avacopan

Avacopan Matching Placebo DRUG

avacopan matching placebo

Also known as: placebo

Avacopan Matching Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• ≥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
• 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
• confirmation of the presence of electron dense deposits in the glomeruli on electron microscopy corresponding with the C3 immunofluorescence positivity;
• 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);
• 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

You may not qualify if:

• Pregnant or nursing;
• Tubulointerstitial fibrosis appears to be more than 50% based on standard assessment using trichrome staining of the renal biopsy;
• Use of eculizumab or another anti-C5 antibody within 26 weeks prior to dosing;
• 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;
• Currently on dialysis or likely will require dialysis within 7 days after screening;
• 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;
• Positive hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) viral screening test indicative of acute or chronic infection;
• 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;
• WBC count less than 3500/μL, or neutrophil count less than 1500/μL, or lymphocyte count less than 500/μL before start of dosing;
• Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin \>3 x the upper limit of normal before start of dosing;
• Currently using a strong inducer of the CYP3A4 enzyme, such as carbamazepine, phenobarbital, phenytoin, rifampin, or St. John's wort;
• Known hypersensitivity to avacopan or inactive ingredients of the avacopan capsules (including gelatin, polyethylene glycol, or Cremophor) or inability to swallow the capsules;
• 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
• 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.

Sponsors & Collaborators

• Amgen: lead
• Medpace, Inc.: collaborator

Study Sites (45)

Clinical Site

Palo Alto, California, 94305, United States

Location

Clinical Site

Chicago, Illinois, 60611, United States

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Clinical Site

Iowa City, Iowa, 52242, United States

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Boston, Massachusetts, 02114, United States

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Clinical Site

New York, New York, 10032, United States

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Rochester, New York, 14625, United States

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Clinical Site

Columbus, Ohio, 43210, United States

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Clinical Site

Philadelphia, Pennsylvania, 19107, United States

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Clinical Trial Site

East Providence, Rhode Island, 02914, United States

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University of Utah

Salt Lake City, Utah, 84132, United States

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Antwerp, Belgium

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Brussels, Belgium

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Leuven, Belgium

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Liège, Belgium

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Vancouver, British Columbia, Canada

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Calgary, Canada

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Aalborg, Denmark

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Copenhagen, Denmark

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Odense, Denmark

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Boulogne-sur-Mer, France

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Grenoble, France

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Paris, France

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Valenciennes, France

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Dresden, Germany

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Essen, Germany

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Hanover, Germany

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Lübeck, Germany

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Munich, Germany

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Dublin, Ireland

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Bergamo, Italy

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Bologna, Italy

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Milan, Italy

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Parma, Italy

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Roma, Italy

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Amsterdam, Netherlands

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Groningen UMC

Groningen, 9713 GZ, Netherlands

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Leiden, Netherlands

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Nijmegen, 6500, Netherlands

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Clinical Site

Nijmegen, 6525, Netherlands

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Barcelona, 08025, Spain

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Barcelona, 08035, Spain

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Clinical Site

Burela de Cabo, Spain

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Madrid, Spain

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London, United Kingdom

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Clinical Site

Newcastle upon Tyne, United Kingdom

Location

Related Publications (1)

• Bomback AS, Herlitz LC, Kedia PP, Petersen J, Yue H, Lafayette RA; ACCOLADE Study Group. Safety and Efficacy of Avacopan in Patients with Complement 3 Glomerulopathy: Randomized, Double-Blind Clinical Trial. J Am Soc Nephrol. 2025 Mar 1;36(3):487-499. doi: 10.1681/ASN.0000000526. Epub 2024 Oct 11.

  PMID: 39392695 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative

Interventions

avacopan

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Immune System Diseases

Results Point of Contact

• Title: Clinical trial disclosure
• Organization: ChemoCentryx, Inc.

clinicaltrials@chemocentryx.com

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matching placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo crossover to active

Study Record Dates

• First Submitted: September 22, 2017
• First Posted: October 4, 2017
• Study Start: September 29, 2017
• Primary Completion: March 3, 2021
• Study Completion: October 27, 2021
• Last Updated: March 13, 2025
• Results First Posted: October 14, 2022

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

CA (2); DE (5); DK (3); ES (4); GB (2); BE (4); NL (5); IE (1); IT (5); FR (4); US (10)