Controlled Trial Evaluating Avacopan in C3 Glomerulopathy

NCT ID: NCT03301467

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-29
• Study Completion Date: 2021-10-27

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

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 acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

Conditions

C3 Glomerulopathy (C3G)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Avacopan

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

Group Type: EXPERIMENTAL

Avacopan

Intervention Type: DRUG

Orally administered

Avacopan Matching Placebo

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

Group Type: PLACEBO_COMPARATOR

Avacopan Matching Placebo

Intervention Type: DRUG

avacopan matching placebo

Interventions

Avacopan

Orally administered

Intervention Type: DRUG

Avacopan Matching Placebo

avacopan matching placebo

Intervention Type: DRUG

Other Intervention Names

CCX168; placebo

Eligibility 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

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medpace, Inc.

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Clinical Site

Palo Alto, California, United States

Clinical Site

Chicago, Illinois, United States

Clinical Site

Iowa City, Iowa, United States

Clinical Site

Boston, Massachusetts, United States

Clinical Site

New York, New York, United States

Clinical Site

Rochester, New York, United States

Clinical Site

Columbus, Ohio, United States

Clinical Site

Philadelphia, Pennsylvania, United States

Clinical Trial Site

East Providence, Rhode Island, United States

University of Utah

Salt Lake City, Utah, United States

Clinical Site

Antwerp, , Belgium

Clinical Site

Brussels, , Belgium

Clinical Site

Leuven, , Belgium

Clinical Site

Liège, , Belgium

Clinical Site

Vancouver, British Columbia, Canada

Clinical Site

Calgary, , Canada

Clinical Site

Aalborg, , Denmark

Clinical Site

Copenhagen, , Denmark

Clinical Site

Odense, , Denmark

Clinical Site

Boulogne-sur-Mer, , France

Clinical Site

Grenoble, , France

Clinical Site

Paris, , France

Clinical Site

Valenciennes, , France

Clinical Site

Dresden, , Germany

Clinical Site

Essen, , Germany

Clinical Site

Hanover, , Germany

Clinical Site

Lübeck, , Germany

Clinical Site

Munich, , Germany

Clinical Site

Dublin, , Ireland

Clinical Site

Bergamo, , Italy

Clinical Site

Bologna, , Italy

Clinical Site

Milan, , Italy

Clinical Site

Parma, , Italy

Clinical Site

Roma, , Italy

Clinical Site

Amsterdam, , Netherlands

Groningen UMC

Groningen, , Netherlands

Clinical Site

Leiden, , Netherlands

Clinical Site

Nijmegen, , Netherlands

Clinical Site

Nijmegen, , Netherlands

Clinical Site

Barcelona, , Spain

Clinical Site

Barcelona, , Spain

Clinical Site

Burela de Cabo, , Spain

Clinical Site

Madrid, , Spain

Clinical Site

London, , United Kingdom

Clinical Site

Newcastle upon Tyne, , United Kingdom

Countries

United States; Belgium; Canada; Denmark; France; Germany; Ireland; Italy; Netherlands; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39392695 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1R01FD006342-01

Identifier Type: FDA

Identifier Source: secondary_id

View Link

CL011_168

Identifier Type: -

Identifier Source: org_study_id