Phase 2
N=6
A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN
C3 Glomerulonephritis · Dense Deposit Disease · C3 Glomerulopathy · Immune Complex Mediated Membranoproliferative Glomerulonephritis · Membranoproliferative Glomerulonephritis Types I, II, and III
Bottom Line
View on ClinicalTrials.gov: NCT03124368 ↗Enrolled (actual)
6
Serious AEs
16.7%
Results posted
Jul 2021
Primary outcome: Primary: Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 — 0.32; 0.56; 0.48; 0.35 g/L
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Danicopan (Drug)
- Age
- Pediatric, Adult, Older Adult · 16+ yrs
- Sex
- All
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 |
0.32; 0.56; 0.48; 0.35; 0.70; 0.58 | — |
| PRIMARY Change From Baseline In Plasma Intact C3 Level On Day 15 |
39.50; 58.25; 52.00; 54.30; 33.50; 40.43 | — |
| SECONDARY Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 |
31.00; 91.00; 71.00; 41.50; 96.75; 78.33 | — |
| SECONDARY Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 |
8.350; 31.073; 23.498; 1.635; 0.993; 1.207 | — |
| SECONDARY Time To Achieving Peak Serum C3 Levels |
2.5; 10.5; 7.8 | — |
| SECONDARY Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation |
2; 3; 5; 0; 1; 1 | — |
| SECONDARY Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) |
871; 2060; 1640; 1120; 2470; 1760 | — |
| SECONDARY PK: Maximum Plasma Concentration (Cmax) |
199; 563; 427; 270; 579; 385 | — |
| SECONDARY PK: Time To Maximum Concentration (Tmax) |
1.00; 2.50; 2.00; 2.75; 2.50; 1.50 | — |
| SECONDARY Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 |
1.789; 1.229; 1.416; 1.511; 0.622; 0.918 | — |
| SECONDARY Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 |
1002.0; 613.750; 743.167; 1105.5; 563.850; 744.400 | — |
Summary
The primary objective of this study was to determine whether ACH-0144471 (also known as danicopan and ALXN2040) increases blood C3 complement protein (C3) levels in participants with low C3 levels due to either C3G or IC-MPGN.
Eligibility Criteria
Key Inclusion Criteria
- Must have had clinical diagnosis of C3G (C3 glomerulonephritis or dense deposit disease, the 2 types of C3G) or idiopathic IC-MPGN by renal biopsy for at least 3 months prior to dosing, with the pathologic diagnosis verified by a review of the renal biopsy by the study central pathologist
- C3 must have been 90% of the lower limit of normal
- Must have been willing to comply with study-specific vaccination requirements for Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis strains A, C, W, and Y
- Negative pregnancy test for females prior to dosing and throughout the study
Key Exclusion Criteria
- History of a major organ transplant (for example, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. Individuals receiving renal replacement therapy were also excluded
- Evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN may have been secondary
- Estimated glomerular filtration rate (using Modification of Diet in Renal Disease equation) 38°Celsius, or other evidence of a clinically significant active infection, within 14 days prior to study drug administration
- History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
- Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration or participants with a female partner who was pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration
Data sourced from ClinicalTrials.gov (NCT03124368). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.