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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03124368




Registration number
NCT03124368
Ethics application status
Date submitted
12/04/2017
Date registered
21/04/2017
Date last updated
4/11/2021

Titles & IDs
Public title
A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN
Scientific 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)
Secondary ID [1] 0 0
2016-003525-42
Secondary ID [2] 0 0
ACH471-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
C3 Glomerulonephritis 0 0
Dense Deposit Disease 0 0
C3 Glomerulopathy 0 0
Immune Complex Mediated Membranoproliferative Glomerulonephritis 0 0
Membranoproliferative Glomerulonephritis Types I, II, and III 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Danicopan

Experimental: Group 1: Danicopan 100 mg TID (Sentinel) - All participants received 100 milligrams (mg) of danicopan three times per day (TID) during the Treatment Period.

Experimental: 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.


Treatment: Drugs: Danicopan
Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
Assessment method [1] 0 0
Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels
Timepoint [1] 0 0
Baseline, Day 15
Primary outcome [2] 0 0
Change From Baseline In Plasma Intact C3 Level On Day 15
Assessment method [2] 0 0
Plasma Intact C3 level were measured by a novel multiplex assay method. Change from Baseline = Plasma Intact C3 levels on Day 15 - Baseline Plasma Intact C3 levels
Timepoint [2] 0 0
Baseline, Day 15
Secondary outcome [1] 0 0
Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14
Assessment method [1] 0 0
CP activity was measured in serum by the DiaSorin Complement Activation Enzyme (CAE) functional immunoassay method, which measures terminal complement complex formation following activation. Results are expressed in CAE units which are calculated relative to previously established CAE activity of a positive control serum. Change from Baseline = Total Complement CP Activity on Day 14 - Baseline Total Complement CP Activity
Timepoint [1] 0 0
Baseline, Day 14
Secondary outcome [2] 0 0
Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15
Assessment method [2] 0 0
AP functional activity was measured in serum by the Wieslab functional immunoassay method, which measures terminal complement complex (TCC) formation following AP-specific activation. Results are expressed as percent TCC production relative to a positive control serum. Change from Baseline = Total Complement AP Functional Activity on Day 15 - Baseline Total Complement AP Functional Activity
Timepoint [2] 0 0
Baseline, Day 15
Secondary outcome [3] 0 0
Time To Achieving Peak Serum C3 Levels
Assessment method [3] 0 0
Serial serum samples were collected on Days 1, 7, and 14.
Timepoint [3] 0 0
From The First Day Of Dosing through Day 14
Secondary outcome [4] 0 0
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
Assessment method [4] 0 0
An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The intensity of an AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Adverse Event Severity Grading Table. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Timepoint [4] 0 0
Up to Day 49
Secondary outcome [5] 0 0
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8)
Assessment method [5] 0 0
Serial blood samples were collected at 0, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose on Days 1 and 7.
Timepoint [5] 0 0
Days 1 and 7
Secondary outcome [6] 0 0
PK: Maximum Plasma Concentration (Cmax)
Assessment method [6] 0 0
Serial blood samples were collected at 0, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose on Days 1 and 7.
Timepoint [6] 0 0
Days 1 and 7
Secondary outcome [7] 0 0
PK: Time To Maximum Concentration (Tmax)
Assessment method [7] 0 0
Serial blood samples were collected at 0, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose on Days 1 and 7.
Timepoint [7] 0 0
Days 1 and 7
Secondary outcome [8] 0 0
Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15
Assessment method [8] 0 0
Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA). Change from Baseline = Complement Bb on Day 15 - Baseline
Timepoint [8] 0 0
Baseline, Day 15
Secondary outcome [9] 0 0
Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15
Assessment method [9] 0 0
Plasma sC5b-9 was measured by ELISA. Change from Baseline = sC5b-9 on Day 15 - Baseline sC5b-9
Timepoint [9] 0 0
Baseline, Day 15

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
16 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/01/2019
Sample size
Target
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Clinical Trial Site - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerpen
Country [2] 0 0
Netherlands
State/province [2] 0 0
Leiden

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Achillion, a wholly owned subsidiary of Alexion
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03124368