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NCT03301467: ACCOLADE

Controlled Trial Evaluating Avacopan in C3 Glomerulopathy

Completed Phase 2 Results posted Last updated 13 March 2025
What this trial tests

Phase 2 trial testing Avacopan in C3 Glomerulopathy (C3G) in 57 participants. Completed in 27 October 2021.

Timeline
29 September 2017
Primary endpoint
3 March 2021
27 October 2021

Quick facts

Lead sponsorAmgen
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment57
Start date29 September 2017
Primary completion3 March 2021
Estimated completion27 October 2021
Sites45 locations across Denmark, France, Italy, Netherlands, Belgium, Ireland, United Kingdom, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

12 and older, any sex, with C3 Glomerulopathy (C3G). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Placebo Group-0.9-2.2 – 0.4
Avacopan Group-1.0-2.3 – 0.4
Percent Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Combined C5b-9 Strata Primary · 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.

GroupValue95% CI
Placebo Group26.20± 47.302
Avacopan Group-5.77± 5.904
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 Secondary · 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

GroupValue95% CI
Placebo Group4
Avacopan Group2
Placebo Group16
Avacopan Group16
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 Secondary · 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

Responder
GroupValue95% CI
Placebo Group7
Avacopan Group4
Non-Responder
GroupValue95% CI
Placebo Group18
Avacopan Group21
Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Subjects With Elevated C5b-9 Secondary · 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

GroupValue95% CI
Placebo Group1.50.9 – 2.2
Avacopan Group1.10.3 – 1.8
Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata Secondary · 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

GroupValue95% CI
Placebo Group1.61.1 – 2.2
Avacopan Group0.80.2 – 1.4
Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 Secondary · 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.

GroupValue95% CI
Placebo Group-4.73-12.29 – 2.83
Avacopan Group6.11-1.86 – 14.08
Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata Secondary · 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.

GroupValue95% CI
Placebo Group-5.88-12.32 – 0.56
Avacopan Group4.79-1.66 – 11.23
Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 Secondary · 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.

GroupValue95% CI
Placebo Group-3.57-8.43 – 1.29
Avacopan Group0.44-4.69 – 5.56
Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata Secondary · 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.

GroupValue95% CI
Placebo Group-3.35-7.56 – 0.85
Avacopan Group0.47-3.75 – 4.68
Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Subjects With Elevated C5b-9 Secondary · 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

GroupValue95% CI
Placebo Group-14-34 – 12
Avacopan Group-16-36 – 12
Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Combined C5b-9 Strata Secondary · 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

GroupValue95% CI
Placebo Group-14-33 – 10
Avacopan Group-26-42 – -6

Adverse events — posted to ClinicalTrials.gov

Time frame: From day 1 throughout the study period (day 182/week 26). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Group
Serious: 3/29 (10%)
Deaths: 0/29
Avacopan Group
Serious: 3/28 (11%)
Deaths: 0/28

Serious adverse events (9 terms)

ReactionSystemPlacebo GroupAvacopan Group
Gastroenteritis salmonellaInfections and infestations
Neutropenic sepsisInfections and infestations
PneumoniaInfections and infestations
Bacterial parotitisInfections and infestations
BronchitisInfections and infestations
Neutrophil count decreasedInvestigations
Sjogren's syndromeMusculoskeletal and connective tissue disorders
Acute kidney injuryRenal and urinary disorders
Alcohol withdrawal syndromePsychiatric disorders
Other adverse events (35 terms — click to expand)

ReactionSystemPlacebo GroupAvacopan Group
Oedema peripheralGeneral disorders
HeadacheNervous system disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Upper respiratory tract infectionInfections and infestations
NasopharyngitisInfections and infestations
DiarrhoeaGastrointestinal disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
Blood creatine phosphokinase increasedInvestigations
Blood creatinine increasedInvestigations
Weight decreasedInvestigations
AnaemiaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
Back painMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Decreased appetiteMetabolism and nutrition disorders
HypertensionVascular disorders
PyrexiaGeneral disorders
InfluenzaInfections and infestations
Lower respiratory tract infectionInfections and infestations
DyspepsiaGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
Lipase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Hand fractureInjury, poisoning and procedural complications
Pain in extremityMusculoskeletal and connective tissue disorders
TremorNervous system disorders
HypokalaemiaMetabolism and nutrition disorders
HyperkalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
AcneSkin and subcutaneous tissue disorders
DepressionPsychiatric disorders
Orthostatic hypotensionVascular disorders

Most-reported serious reactions: Gastroenteritis salmonella, Neutropenic sepsis, Pneumonia, Bacterial parotitis, Bronchitis, Neutrophil count decreased, Sjogren's syndrome, Acute kidney injury.

Data from ClinicalTrials.gov NCT03301467 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. New insights into the immune functions of complement.
    Reis ES, Mastellos DC, Hajishengallis G, Lambris JD. · · 2019 · cited 357× · PMID 31048789 · DOI 10.1038/s41577-019-0168-x
  2. Clinical promise of next-generation complement therapeutics.
    Mastellos DC, Ricklin D, Lambris JD. · · 2019 · cited 255× · PMID 31324874 · DOI 10.1038/s41573-019-0031-6
  3. Glomerulonephritis: immunopathogenesis and immunotherapy.
    Anders HJ, Kitching AR, Leung N, Romagnani P. · · 2023 · cited 105× · PMID 36635359 · DOI 10.1038/s41577-022-00816-y
  4. Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease.
    Wang N, Zhang C. · · 2024 · cited 95× · PMID 38671903 · DOI 10.3390/antiox13040455
  5. Complement Inhibitors in Clinical Trials for Glomerular Diseases.
    Zipfel PF, Wiech T, Rudnick R, Afonso S, et al · · 2019 · cited 89× · PMID 31611870 · DOI 10.3389/fimmu.2019.02166
  6. Complement Factor D as a Strategic Target for Regulating the Alternative Complement Pathway.
    Barratt J, Weitz I. · · 2021 · cited 88× · PMID 34566967 · DOI 10.3389/fimmu.2021.712572
  7. Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage.
    Franzin R, Stasi A, Fiorentino M, Stallone G, et al · · 2020 · cited 74× · PMID 32457738 · DOI 10.3389/fimmu.2020.00734
  8. Alternative Complement Pathway Inhibition With Iptacopan for the Treatment of C3 Glomerulopathy-Study Design of the APPEAR-C3G Trial.
    Bomback AS, Kavanagh D, Vivarelli M, Meier M, et al · · 2022 · cited 51× · PMID 36217526 · DOI 10.1016/j.ekir.2022.07.004

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing