A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN

NCT ID: NCT03124368

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-09
• Study Completion Date: 2019-01-09

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Group 1: Danicopan 100 mg TID (Sentinel)

All participants received 100 milligrams (mg) of danicopan three times per day (TID) during the Treatment Period.

Group Type: EXPERIMENTAL

Danicopan

Intervention Type: DRUG

Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).

Group 2: Danicopan up to 200 mg TID

All participants received not more than 200 mg of danicopan TID depending on the available safety, pharmacokinetic, and pharmacodynamic data from Group 1 (Sentinel) during the Treatment Period.

Group Type: EXPERIMENTAL

Danicopan

Intervention Type: DRUG

Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).

Interventions

Danicopan

Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).

Intervention Type: DRUG

Other Intervention Names

ACH-4471; ACH4471; 4471; ACH-0144471; ALXN2040

Eligibility Criteria

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

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Achillion, a wholly owned subsidiary of Alexion

INDUSTRY

Sponsor Role: collaborator

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Trial Site

Melbourne, , Australia

Clinical Trial Site

Antwerp, , Belgium

Clinical Trial Site

Leiden, , Netherlands

Countries

Australia; Belgium; Netherlands

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-003525-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACH471-201

Identifier Type: -

Identifier Source: org_study_id