A Proof-of-Concept Study of Danicopan for 6 Months of Treatment in Participants With C3 Glomerulopathy (C3G)

Phase 2

Completed

Brief Summary: The primary purpose of this proof-of-concept clinical study was to evaluate the efficacy and safety of the study drug, ACH-0144471 (also known as danicopan and ALXN2040), in participants with C3G who also had significant proteinuria attributable to C3G.

Recruitment & Eligibility

Inclusion Criteria

Had biopsy-confirmed primary C3G
Had clinical evidence of ongoing disease based on significant proteinuria, attributable to C3G disease in the opinion of the Principal Investigator (PI), and present prior to study entry and confirmed during Screening
Was willing to comply with vaccination requirements.

Key

Exclusion Criteria

Had a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study
Had ever received danicopan
Had more than 50% fibrosis or more than 50% of glomeruli with cellular crescents on the pre-treatment renal biopsy
Had an estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared at the time of screening or at any time over the preceding 4 weeks
Was a renal transplant recipient or receiving renal replacement therapy
Had a history of a major organ transplant or hematopoietic stem cell/marrow transplant
Had evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G is secondary
Had other renal diseases that would interfere with interpretation of the study
Had been diagnosed with or showed evidence of hepatobiliary cholestasis
Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration
Had a history of febrile illness, a body temperature >38°Celsius, or other evidence of a clinically significant active infection, within 14 days prior to study drug administration
Had evidence of human immunodeficiency virus, hepatitis B infection, or active hepatitis C infection at Screening
Had laboratory abnormalities at screening that, in the opinion of the PI, would make the participant inappropriate for the study

Arm && Interventions

Group	Intervention	Description
Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)	Danicopan	Danicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.
Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)	Placebo	Placebo was administered TID during the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.
Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)	Danicopan	Placebo was administered TID during the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.

Primary Outcome Measures

Name	Time	Method
Change From Baseline In Composite Biopsy Score At Week 28	Baseline, Week 28	The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of 6 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
Participants With Reduction In Proteinuria At Week 28	Week 28	Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).

Secondary Outcome Measures

Name	Time	Method
Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment	12 months	Slope of eGFR was estimated using a simple linear regression for each participant, including all data values during the open-label extension period with eGFR as the dependent variable and time as the independent variable.
Change From Baseline In eGFR At Week 28	Baseline, Week 28	Change from baseline in eGFR at Week 28 is presented.
Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months	6 months	Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the 6-month blinded treatment period, with eGFR as the dependent variable and time as the independent variable.
Participants With Significant Improvement In eGFR Relative To Baseline At Week 28	Baseline, Week 28	Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.
Change From Baseline In Proteinuria At Week 28	Baseline, Week 28	Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.
Percent Change From Baseline In Proteinuria At Week 28	Baseline, Week 28	Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.
Participants With Significant Improvement In eGFR Relative To Baseline At Week 52	Baseline, Week 52	Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.