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

A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, Placebo-Controlled Study of ACH-0144471 Treatment for 6 Months in Patients With C3 Glomerulopathy (C3G), With an Open-label Extension

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.

Study Overview

• Status: Completed
• Conditions: C3 Glomerulopathy; C3 Glomerulonephritis; Dense Deposit Disease
• Intervention / Treatment: Drug: Danicopan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Clinical Study Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical Study Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Clinical Study Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Clinical Study Site
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Clinical Study Site
  • New York
    • New York, New York, United States, 10016
      • Clinical Study Site
    • New York, New York, United States, 10032
      • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period); 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.	Drug: Danicopan; Danicopan was administered as an oral tablet.; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471
Placebo Comparator: Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period); 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.	Drug: Danicopan; Danicopan was administered as an oral tablet.; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471; Drug: Placebo; Matching placebo was administered as an oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline In Composite Biopsy Score At 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.	Baseline, Week 28
Participants With Reduction In Proteinuria At Week 28	Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).	Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline In Proteinuria At Week 28	Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.	Baseline, Week 28
Percent Change From Baseline In Proteinuria At Week 28	Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.	Baseline, Week 28
Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 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.	6 months
Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment	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.	12 months
Change From Baseline In eGFR At Week 28	Change from baseline in eGFR at Week 28 is presented.	Baseline, Week 28
Participants With Significant Improvement In eGFR Relative To Baseline At Week 28	Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.	Baseline, Week 28
Participants With Significant Improvement In eGFR Relative To Baseline At Week 52	Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2018
• Primary Completion (Actual): December 11, 2019
• Study Completion (Actual): December 18, 2020

Study Registration Dates

• First Submitted: November 17, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): October 14, 2022
• Last Update Submitted That Met QC Criteria: October 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: DDD; MPGN; C3GN; factor D; fD; Primary MPGN; Mesangiocapillary Glomerulonephritis; Membranoproliferative Glomerulonephritis; Alternative pathway; Complement mediated disease; Idiopathic MPGN
• Additional Relevant MeSH Terms: Immune System Diseases; Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Glomerulonephritis, Membranoproliferative
• Other Study ID Numbers: ACH471-204; 2017-000663-33 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes