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

Alexion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: C3 Glomerulopathy; Immune Complex Mediated Membranoproliferative Glomerulonephritis; Dense Deposit Disease; Membranoproliferative Glomerulonephritis Types I, II, and III; C3 Glomerulonephritis

Treatments: Drug: Danicopan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03124368

2016-003525-42 (EudraCT Number)

ACH471-201

Details and patient eligibility

About

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.

Enrollment: 6 patients

Sex: All

Ages: 16 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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6 participants in 2 patient groups

Group 1: Danicopan 100 mg TID (Sentinel)

Experimental group

Description:

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

Treatment:

Drug: Danicopan

Group 2: Danicopan up to 200 mg TID

Experimental group

Description:

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.

Treatment:

Drug: Danicopan