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

C3 Glomerulopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03369236
• Other study ID #: ACH471-204
• Secondary ID: 2017-000663-33
• Status: Completed
• Phase: Phase 2
• Start date: June 12, 2018
• Est. completion date: December 18, 2020

Study information

• Verified date: October 2022
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: December 18, 2020
• Est. primary completion date: December 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• C3 Glomerulonephritis
• C3 Glomerulopathy
• Dense Deposit Disease
• Glomerulonephritis
• Glomerulonephritis, Membranoproliferative

Intervention

Drug:
• Danicopan
Danicopan was administered as an oral tablet.
• Placebo
Matching placebo was administered as an oral tablet.

Locations

Country	Name	City	State
United Kingdom	Clinical Study Site	London
United States	Clinical Study Site	Aurora	Colorado
United States	Clinical Study Site	Baltimore	Maryland
United States	Clinical Study Site	Iowa City	Iowa
United States	Clinical Study Site	Lawrenceville	Georgia
United States	Clinical Study Site	New York	New York
United States	Clinical Study Site	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline In eGFR At Week 28	Change from baseline in eGFR at Week 28 is presented.	Baseline, Week 28
Secondary	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
Secondary	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