A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN
Condition: C3 Glomerulonephritis; Dense Deposit Disease; C3 Glomerulopathy; Immune Complex Mediated Membranoproliferative Glomerulonephritis; Membranoproliferative Glomerulonephritis Types I, II, and III
MeSH terms: Glomerulonephritis; Glomerulonephritis, Membranoproliferative
Intervention: Danicopan
Intervention description: Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 16 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: factor D; FD; alternative pathway; complement mediated disease; idiopathic MPGN; MPGN Type I; MPGN Type II; MPGN Type III; Primary MPGN; MCGN; Mesangiocapillary Glomerulonephritis; C3 Glomerulopathy; C3G; Membranoproliferative Glomerulonephritis; C3GN; Dense Deposit Disease; DDD

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 <50% of the lower limit of normal

          -  C4 complement protein (C4) 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) <45 milliliters/minute/1.73 square meters at the time of Screening or at any
             time over the preceding 4 weeks

          -  Receipt of eculizumab at any dose or interval within the past 75 days prior to dosing

          -  Use of tacrolimus or cyclosporine within 2 weeks of the first dose of danicopan

          -  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

          -  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