A Proof of Concept Study for a 12 Month Treatment in Patients With C3G or IC-MPGN Treated With ACH-0144471
Condition: C3 Glomerulonephritis; C3 Glomerulopathy; Immune Complex Membranoproliferative Glomerulonephritis; IC-MPGN; Dense Deposit Disease
MeSH terms: Glomerulonephritis; Glomerulonephritis, Membranoproliferative
Intervention: Danicopan
Intervention description: Danicopan was to be administered as an oral tablet.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: factor D; fD; alternative pathway; complement mediated disease; C3GN; DDD; idiopathic MPGN; MPGN Type I; MPGN Type II; MPGN Type III; Primary MPGN; MCGN; Mesangiocapillary Glomerulonephritis

Summary:

      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.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. At least 12 years of age

          2. Completion of the ACH471-201 clinical study OR diagnosed with biopsy-confirmed primary
             C3G or IC-MPGN

          3. If a pre-treatment biopsy is obtained, or if a historical biopsy is available for
             review, it must have no more than 50% global fibrosis and no more than 50% of
             glomeruli with cellular crescents

          4. Clinical evidence of ongoing disease based on significant proteinuria (defined as ≥500
             mg/day of protein in a 24-hour urine) attributable to C3G disease or IC-MPGN in the
             opinion of the principal investigator (PI), and present prior to study entry and
             confirmed during Screening

          5. If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications
             (for example, angiotensin-converting enzyme inhibitors or angiotensin receptor
             blockers), or mycophenolate mofetil, must be on a stable dose for at least 2 weeks
             prior to screening

          6. Female participants must use an acceptable method birth control to prevent pregnancy
             during the clinical study and for 30 days after the last dose of study medication

          7. Male participants must use highly effective birth control with a female partner to
             prevent pregnancy during the clinical study and for 90 days after the last dose of
             study medication

          8. Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based
             on local guidelines

          9. Must have access to emergency medical care

        Key Exclusion Criteria

          1. Have a history of a major organ transplant (for example, heart, lung, kidney, or
             liver) or hematopoietic stem cell/marrow transplant

          2. Have a history or presence of any clinically relevant co-morbidities that would make
             the participant inappropriate for the study (for example, a comorbidity that is likely
             to result in deterioration of the participant's condition, affect the participant's
             safety during the study, or confound the results of the study), in the opinion of the
             PI

          3. Have an eGFR <30 milliliter/minute/1.73 m^2 at the time of screening or at any time
             over the preceding 4 weeks

          4. Is a renal transplant recipient or receiving renal replacement therapy

          5. Have other renal diseases that would interfere with the interpretation of the study

          6. Have evidence of monoclonal gammopathy of unclear significance, infections,
             malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN is
             secondary

          7. Have been diagnosed with or show evidence of hepatobiliary cholestasis

          8. Females who are pregnant, nursing, or planning to become pregnant during the study or
             within 90 days of ACH-0144471 administration or participants with a female partner who
             is pregnant, nursing, or planning to become pregnant during the study or within 90
             days of ACH-0144471 administration

          9. Have a history of febrile illness, a body temperature >38°Celsius, or other evidence
             of a clinically significant active infection, within 14 days prior to danicopan
             administration

         10. Have evidence of human immunodeficiency virus, hepatitis B infection, or active
             hepatitis C infection at Screening

         11. Have a history of meningococcal infection within the prior year

         12. Have a history of hypersensitivity reactions to commonly used antibacterial agents,
             including beta-lactams, penicillin, aminopenicillins, fluoroquinolones,
             cephalosporins, and carbapenems, which, in the opinion of the investigator and/or an
             appropriately qualified immunology or infectious disease expert, would make it
             difficult to properly provide either empiric antibiotic therapy or treat an active
             infection.

         13. Have participated in a clinical study in which an investigational drug was given
             within 30 days, or within 5 half-lives of the investigational drug, whichever is
             longer, prior to the first dose of ACH-0144471

         14. Have received eculizumab at any dose or interval within the past 50 days prior to the
             first dose of ACH-0144471

         15. Have received tacrolimus or cyclosporine within 2 weeks of the first dose of
             ACH-0144471

         16. Have a 12-lead electrocardiogram (ECG) with a QT interval Fridericia correction
             formula >450 millisecond (msec) for males or >470 msec for females, or have ECG
             findings which, in the opinion of the PI, could put the participant at undue risk

         17. Have received any drug known to prolong the corrected QT interval within 2 weeks of
             the first dose of ACH-0144471 and which, in the opinion of the PI, could put the
             participant at undue risk

         18. Have any of the following laboratory abnormalities at screening:

               -  Alanine transaminase > upper limit of normal (ULN)

               -  Aspartate aminotransferase > ULN

               -  Absolute neutrophil counts <1,000/microliter

               -  Total bilirubin >1.5* ULN

               -  Indirect bilirubin > ULN

               -  Any laboratory abnormality that, in the opinion of the PI, would make the
                  participant inappropriate for the study

         19. Unwilling or unable to comply with the study protocol for any reason