A Proof-of-Concept Study of Danicopan for 6 Months of Treatment in Participants With C3 Glomerulopathy (C3G)
Condition: C3 Glomerulopathy; C3 Glomerulonephritis; Dense Deposit Disease
MeSH terms: Glomerulonephritis; Glomerulonephritis, Membranoproliferative
Intervention: Danicopan; Placebo
Intervention description: Danicopan was administered as an oral tablet.; Matching placebo was administered as an oral tablet.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
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.
Enrollment: 13.0
Sex: All
Minimum age: 17 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: factor D; fD; Alternative pathway; Complement mediated disease; Membranoproliferative Glomerulonephritis; Primary MPGN; MPGN; Mesangiocapillary Glomerulonephritis; Idiopathic MPGN; DDD; C3GN

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.
    

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