C3 Glomerulopathy (C3G)Phase 2ACCOLADENCT03301467
Controlled Trial Evaluating Avacopan in C3 Glomerulopathy
A Phase 2 study testing Avacopan in people with C3 Glomerulopathy (C3G), run by Amgen at 45 sites in 11 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- C3 Glomerulopathy (C3G)
- What is being tested?
- Avacopan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 45 sitesin 11 countries
- Study dates
- 29 Sep 2017to 27 Oct 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
- 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.
Who cannot join
- 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;
Show all 14Show fewer
- 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.
Trial locations and contacts
45 sites in 11 countries.
45 sites in 11 countries
United States10 sites
Clinical Site
Boston, Massachusetts, 02114
Clinical Site
Chicago, Illinois, 60611
Clinical Site
Columbus, Ohio, 43210
Clinical Trial Site
East Providence, Rhode Island, 02914
Clinical Site
Iowa City, Iowa, 52242
Clinical Site
New York, New York, 10032
Clinical Site
Palo Alto, California, 94305
Clinical Site
Philadelphia, Pennsylvania, 19107
Clinical Site
Rochester, New York, 14625
University of Utah
Salt Lake City, Utah, 84132
Germany5 sites
Clinical Site
Dresden
Clinical Site
Essen
Clinical Site
Hanover
Clinical Site
Lübeck
Clinical Site
Munich
Italy5 sites
Clinical Site
Bergamo
Clinical Site
Bologna
Clinical Site
Milan
Clinical Site
Parma
Clinical Site
Roma
Netherlands5 sites
Clinical Site
Amsterdam
Groningen UMC
Groningen, 9713 GZ
Clinical Site
Leiden
Clinical Site
Nijmegen, 6500
Clinical Site
Nijmegen, 6525
Belgium4 sites
Clinical Site
Antwerp
Clinical Site
Brussels
Clinical Site
Leuven
Clinical Site
Liège
France4 sites
Clinical Site
Boulogne-sur-Mer
Clinical Site
Grenoble
Clinical Site
Paris
Clinical Site
Valenciennes
Spain4 sites
Clinical Site
Barcelona, 08025
Clinical Site
Barcelona, 08035
Clinical Site
Burela de Cabo
Clinical Site
Madrid
Denmark3 sites
Clinical Site
Aalborg
Clinical Site
Copenhagen
Clinical Site
Odense
United Kingdom2 sites
Clinical Site
London
Clinical Site
Newcastle upon Tyne
About this study
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
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
Read the 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)
- Being tested
- Avacopan, Avacopan Matching Placebo
- Keywords
- C3 Glomerulonephritis, C3 glomerulopathy, C3G, DDD, dense deposit disease, membranoproliferative glomerulonephritis, MPGN, C3GN, idiopathic MPGN
- Medical subject headings
- Glomerulonephritis, Membranoproliferative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvacopanDrug
Also called CCX168
Orally administered
Avacopan Matching PlaceboDrug
Also called placebo
avacopan matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Avacopan | Experimental | Avacopan (formerly CCX168) 10 mg capsules x 3 administered twice daily during the blinded 26 week blinded treatment period Receives: Drug: Avacopan |
| Avacopan Matching Placebo | Placebo comparator | Matching placebo capsules x 3 administered twice daily during the 26 week blinded treatment period period Receives: Drug: Avacopan Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
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
Measured: 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
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
Measured: Week 26
Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Subjects With Elevated C5b-9
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
Measured: Week 26
Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata
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
Measured: Week 26
Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9
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.
Measured: Week 26
Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata
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.
Measured: Week 26
Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9
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.
Measured: Week 26
Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata
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.
Measured: Week 26
Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Subjects With Elevated C5b-9
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
Measured: Week 26
Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Combined C5b-9 Strata
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
Measured: Week 26
Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Subjects With Elevated C5b-9
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
Measured: Week 26
Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Combined C5b-9 Strata
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
Measured: Week 26
Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects With Elevated C5b-9
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).
Measured: Week 26
Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata
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).
Measured: Week 26
Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9
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).
Measured: Week 26
Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata
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).
Measured: Week 26
Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs
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
Measured: 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
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
Measured: From day 1 throughout the study period (day 182/week 26)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2017
- Study start29 Sep 2017
- Primary completion3 Mar 2021
- Study completion27 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for C3 Glomerulopathy (C3G)Studies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo crossover to active
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03301467
- Sponsor's protocol ID
- CL011_168
- Other IDs
- 1R01FD006342-01
- Acronym
- ACCOLADE
- Status last verified
- Mar 2025
- First submitted
- 22 Sep 2017
- Last updated
- 13 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
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.
PubMed 39392695
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03301467
- Acronym / sponsor ID
- ACCOLADE / CL011_168
- Conditions
- C3 Glomerulopathy (C3G)
- Keywords
- C3 Glomerulonephritis, C3 glomerulopathy, C3G, DDD, dense deposit disease, membranoproliferative glomerulonephritis, MPGN, C3GN
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Study start
- 29 Sep 2017 (actual)
- Primary completion
- 3 Mar 2021 (actual)
- Study completion
- 27 Oct 2021 (actual)
- First posted
- 4 Oct 2017 (actual)
- Results
- Posted 14 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Placebo crossover to active
| Arm | Type | Receives |
|---|---|---|
| Avacopan | Experimental | Drug: AvacopanAvacopan (formerly CCX168) 10 mg capsules x 3 administered twice daily during the blinded 26 week blinded treatment period |
| Avacopan Matching Placebo | Placebo comparator | Drug: Avacopan Matching PlaceboMatching placebo capsules x 3 administered twice daily during the 26 week blinded treatment period period |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- 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
- 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.
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvacopanAlso: CCX168Orally administered | Drug | Avacopan |
| Avacopan Matching PlaceboAlso: placeboavacopan matching placebo | Drug | Avacopan Matching Placebo |
Primary outcome
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
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.
18 secondary outcomes
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 - Combined C5b-9 Strata
Time frame: Week 26
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 C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata
Time frame: Week 26
Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9
Time frame: Week 26
Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata
Time frame: Week 26
Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9
Time frame: Week 26
Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata
Time frame: Week 26
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 - Combined C5b-9 Strata
Time frame: Week 26
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 - Combined C5b-9 Strata
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
Time frame: Week 26
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 SF-36 v2 - Subjects With Elevated C5b-9
Time frame: Week 26
Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata
Time frame: Week 26
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 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39392695Bomback 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.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
45 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avacopan in people with C3 Glomerulopathy (C3G), run by Amgen at 45 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Germany, Italy, Netherlands, Belgium and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Subjects With Elevated C5b-9 (time frame: Week 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03301467, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.