Back to resultsA Proof-of-Concept Study of Danicopan for 6 Months of Treatment in Participants With C3 Glomerulopathy (C3G)
Primary Purpose
C3 Glomerulopathy, C3 Glomerulonephritis, Dense Deposit Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Danicopan
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for C3 Glomerulopathy focused on measuring factor D, fD, Alternative pathway, Complement mediated disease, Membranoproliferative Glomerulonephritis, Primary MPGN, MPGN, Mesangiocapillary Glomerulonephritis, Idiopathic MPGN, DDD, C3GN
Eligibility Criteria
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
Sites / Locations
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)
Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)
Arm Description
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 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.
Outcomes
Primary Outcome Measures
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.
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).
Secondary Outcome Measures
Change From Baseline In Proteinuria At 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
Proteinuria was assessed based on 24-hour urine collections at baseline and 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.
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.
Change From Baseline In eGFR At Week 28
Change from baseline in eGFR at Week 28 is presented.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03369236
Brief Title
A Proof-of-Concept Study of Danicopan for 6 Months of Treatment in Participants With C3 Glomerulopathy (C3G)
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
June 12, 2018 (Actual)
Primary Completion Date
December 11, 2019 (Actual)
Study Completion Date
December 18, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
C3 Glomerulopathy, C3 Glomerulonephritis, Dense Deposit Disease
Keywords
factor D, fD, Alternative pathway, Complement mediated disease, Membranoproliferative Glomerulonephritis, Primary MPGN, MPGN, Mesangiocapillary Glomerulonephritis, Idiopathic MPGN, DDD, C3GN
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Investigator and participant blinded; Sponsor open. Participants were randomized 1:1 to receive either danicopan or placebo for a period of 6 months, followed by an open-label extension.
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Danicopan
Other Intervention Name(s)
ACH-4471, ACH4471, 4471, ACH-0144471 (formerly), ALXN2040
Intervention Description
Danicopan was administered as an oral tablet.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo was administered as an oral tablet.
Primary Outcome Measure Information:
Title
Change From Baseline In Composite Biopsy Score At Week 28
Description
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.
Time Frame
Baseline, Week 28
Title
Participants With Reduction In Proteinuria At Week 28
Description
Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).
Time Frame
Week 28
Secondary Outcome Measure Information:
Title
Change From Baseline In Proteinuria At Week 28
Description
Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.
Time Frame
Baseline, Week 28
Title
Percent Change From Baseline In Proteinuria At Week 28
Description
Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.
Time Frame
Baseline, Week 28
Title
Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months
Description
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.
Time Frame
6 months
Title
Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment
Description
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.
Time Frame
12 months
Title
Change From Baseline In eGFR At Week 28
Description
Change from baseline in eGFR at Week 28 is presented.
Time Frame
Baseline, Week 28
Title
Participants With Significant Improvement In eGFR Relative To Baseline At Week 28
Description
Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.
Time Frame
Baseline, Week 28
Title
Participants With Significant Improvement In eGFR Relative To Baseline At Week 52
Description
Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.
Time Frame
Baseline, Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
17 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Clinical Study Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Clinical Study Site
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30046
Country
United States
Facility Name
Clinical Study Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Clinical Study Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Clinical Study Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Clinical Study Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Clinical Study Site
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Proof-of-Concept Study of Danicopan for 6 Months of Treatment in Participants With C3 Glomerulopathy (C3G)
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