Clinical trial NCT03124368: A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN
Official title: A Phase 2a Proof-of-Mechanism, Open-Label Study to Determine the Effect of ACH-0144471 on C3 Levels in Participants With Low C3 Levels Due to Either C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: C3 Glomerulonephritis
Dense Deposit Disease
C3 Glomerulopathy
Immune Complex Mediated Membranoproliferative Glomerulonephritis
Membranoproliferative Glomerulonephritis Types I, II, and III
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
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Achillion, a wholly owned subsidiary of Alexion
First posted: 2017-04-21
Enrollment: 6
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief 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

Primary outcomes:
measure: Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
timeFrame: Baseline, Day 15
measure: Change From Baseline In Plasma Intact C3 Level On Day 15
timeFrame: Baseline, Day 15
Secondary outcomes:
measure: Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14
timeFrame: Baseline, Day 14
measure: Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15
timeFrame: Baseline, Day 15
measure: Time To Achieving Peak Serum C3 Levels
timeFrame: From The First Day Of Dosing through Day 14
measure: 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
timeFrame: Up to Day 49
measure: Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8)
timeFrame: Days 1 and 7
measure: PK: Maximum Plasma Concentration (Cmax)
timeFrame: Days 1 and 7
measure: PK: Time To Maximum Concentration (Tmax)
timeFrame: Days 1 and 7
measure: Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15
timeFrame: Baseline, Day 15
measure: Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15
timeFrame: Baseline, Day 15
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Clinical Trial Site
city: Antwerpen
country: Belgium
facility: Clinical Trial Site
city: Leiden
country: Netherlands
facility: Clinical Trial Site
Study officials:
References: