A Phase 2 interventional study of Danicopan in C3 Glomerulonephritis, C3 Glomerulopathy and Immune Complex Membranoproliferative Glomerulonephritis, sponsored by Alexion Pharmaceuticals, Inc.. Terminated at 13 sites in 5 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2023-08-21.
Sponsored by Alexion Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment
The primary purpose of this study was to evaluate the efficacy of 12 months of oral ACH-0144471 (also known as danicopan and ALXN2040) in participants with C3G or IC-MPGN based on histologic scoring and proteinuria.
This was an open-label study to evaluate the efficacy of treatment with danicopan in participants 12 years of age or older with biopsy-confirmed C3G or IC-MPGN who had not undergone renal transplantation. All participants were to receive active treatment with danicopan for approximately 40 months. The starting dosage was to be 100 mg TID, and after 2 weeks, the dosage was to be increased to 200 mg TID for participants with body weight ≥ 60 kg or 150 mg TID for participants with body weight \< 60 kg. Planned enrollment was approximately 20 participants.
Key Inclusion Criteria:
Key Exclusion Criteria
Have any of the following laboratory abnormalities at screening:
Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Drug: Danicopan
Danicopan was to be administered as an oral tablet.
Also known as: ACH-4471, ACH4471, 4471, ALXN2040
Change From Baseline In Composite Biopsy Score At End Of Initial 12-Month Treatment Period
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 the initial 12 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
Time frame: Baseline, end of initial 12-Month Treatment Period
Participants With Reduction In Proteinuria At End Of Initial 12-Month Treatment Period
Proteinuria reduction was defined as ≥30% decrease from baseline based on 24-hour urine protein (mg/day).
Time frame: Baseline, end of initial 12-Month Treatment Period
Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period
Proteinuria was assessed based on 24-hour urine collections at baseline and end of the initial 12-month Treatment Period.
Time frame: Baseline, end of initial 12-Month Treatment Period
Percent Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period
Proteinuria was assessed based on 24-hour urine collections at baseline and end of initial 12-month Treatment Period.
Time frame: Baseline, end of initial 12-Month Treatment Period
Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To End Of Initial 12-Month Treatment Period
Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the Initial 12-Month Treatment Period, with eGFR as the dependent variable and time as the independent variable.
Time frame: End of initial 12-Month Treatment Period
Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period
Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.
Time frame: Baseline, end of initial 12-Month Treatment Period
Participants With Significant Improvement In eGFR Relative To Baseline At End Of Initial 12-Month Treatment Period
Significant improvement relative to baseline was defined as a ≥ 25% increase from baseline in eGFR.
Time frame: Baseline, end of initial 12-Month Treatment Period
Change From Baseline in eGFR Over 12 Months of Treatment For Participants Meeting eGFR Inclusion Criteria
Participants were eligible for enrollment if inclusion criteria were met including having an eGFR \>=30 milliliters (mL)/minute (min)/1.73 square meter (m\^2) at the time of screening or at any time over the preceding 4 weeks. This Outcome Measure was registered in case there were participants who were enrolled and ended up not meeting the Eligibility Criteria and was intended to report data for change from baseline in eGFR for only the participants who met the eligibility criteria (that is, participants who did not meet the eligibility criteria would have been excluded from analysis for this Outcome Measure). Since all enrolled participants met the Eligibility Criteria, none of the participants were excluded from this analysis. Therefore, this data is the same data that is presented in Outcome Measure #6 "Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period". Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.
Time frame: End of initial 12-Month Treatment Period
Change From Baseline In Measured GFR At The End Of The Initial 12-Month Treatment Period
Data for this Outcome Measure was to be collected where available. None of the sites collected data for this Outcome Measure.
Time frame: End of initial 12-Month Treatment Period
| Milestone | Danicopan |
|---|---|
| Started | 22 |
| Received at least 1 dose of study drug | 22 |
| Completed | 0 |
| Not completed | 22 |
| Withdrew: Lack of efficacy | 3 |
| Withdrew: Adverse event | 1 |
| Withdrew: Sponsor's decision to close the study | 18 |
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 the initial 12 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
| score on a scale | Danicopan |
|---|---|
| Baseline | 10.6 ± 3.59 |
| End of 12-Month Initial Treatment Period | 8.0 ± 4.53 |
| Change from Baseline | -0.9 ± 1.89 |
Proteinuria reduction was defined as ≥30% decrease from baseline based on 24-hour urine protein (mg/day).
| participants | Danicopan |
|---|---|
| Participants With Reduction In Proteinuria At End Of Initial 12-Month Treatment Period | 8 |
Proteinuria was assessed based on 24-hour urine collections at baseline and end of the initial 12-month Treatment Period.
| mg/day | Danicopan |
|---|---|
| Baseline | 4252.28 ± 2684.959 |
| End of Initial 12-Month Treatment Period | 3512.63 ± 3335.765 |
| Mean Change from Baseline | -671.11 ± 2695.592 |
Proteinuria was assessed based on 24-hour urine collections at baseline and end of initial 12-month Treatment Period.
| percent change | Danicopan |
|---|---|
| Percent Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period | -17.1 ± 53.17 |
Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the Initial 12-Month Treatment Period, with eGFR as the dependent variable and time as the independent variable.
| mL/min/1.73 m^2 per month | Danicopan |
|---|---|
| Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To End Of Initial 12-Month Treatment Period | -1.24917 ± 1.811457 |
Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.
| mL/min/1.73 m^2 | Danicopan |
|---|---|
| Baseline | 90.692 ± 35.4939 |
| End of Initial 12-Month Treatment Period | 81.412 ± 38.3320 |
| Change from Baseline | -9.795 ± 14.3806 |
Significant improvement relative to baseline was defined as a ≥ 25% increase from baseline in eGFR.
| participants | Danicopan |
|---|---|
| Participants With Significant Improvement In eGFR Relative To Baseline At End Of Initial 12-Month Treatment Period | 0 |
Participants were eligible for enrollment if inclusion criteria were met including having an eGFR \>=30 milliliters (mL)/minute (min)/1.73 square meter (m\^2) at the time of screening or at any time over the preceding 4 weeks. This Outcome Measure was registered in case there were participants who were enrolled and ended up not meeting the Eligibility Criteria and was intended to report data for change from baseline in eGFR for only the participants who met the eligibility criteria (that is, participants who did not meet the eligibility criteria would have been excluded from analysis for this Outcome Measure). Since all enrolled participants met the Eligibility Criteria, none of the participants were excluded from this analysis. Therefore, this data is the same data that is presented in Outcome Measure #6 "Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period". Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.
| mL/min/1.73 m^2 | Danicopan |
|---|---|
| Baseline | 90.692 ± 35.4939 |
| End of Initial 12-Month Treatment Period | 81.412 ± 38.3320 |
| Change from Baseline | -9.795 ± 14.3806 |
Data for this Outcome Measure was to be collected where available. None of the sites collected data for this Outcome Measure.
No measurements were reported for this outcome.
Collected over Day 1 (after dosing) up to 4 weeks after last dose of study drug (up to Week 108). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Danicopan | 0/22 (0%) | 3/22 (13.6%) | 22/22 (100%) |
| Event | Danicopan |
|---|---|
| Atrial fibrillationCardiac disorders | 1/22 |
| PyrexiaGeneral disorders | 1/22 |
| Rhinovirus infectionInfections and infestations | 1/22 |
| Renal impairmentRenal and urinary disorders | 1/22 |
| Event | Danicopan |
|---|---|
| PyrexiaGeneral disorders | 11/22 |
| Oedema peripheralGeneral disorders | 8/22 |
| VomitingGastrointestinal disorders | 6/22 |
| GastroenteritisInfections and infestations | 6/22 |
| PharyngitisInfections and infestations | 6/22 |
| HeadacheNervous system disorders | 6/22 |
| AnaemiaBlood and lymphatic system disorders | 5/22 |
| DiarrhoeaGastrointestinal disorders | 5/22 |
| FatigueGeneral disorders | 5/22 |
| Blood creatine phosphokinase increasedInvestigations | 5/22 |
All participants who received at least 1 dose of study drug during treatment period.
| Age, Continuous(years) | Danicopan |
|---|---|
| Mean | 24.3 ± 9.90 |
| Sex: Female, Male(Participants) | Danicopan |
|---|---|
| Female | 10 |
| Male | 12 |
| Ethnicity (NIH/OMB)(Participants) | Danicopan |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 22 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Danicopan |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 1 |
| Black or African American | 0 |
| White | 19 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
Supporting information: Sap, Csr
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Alexion Pharmaceuticals, Inc.