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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
Timepoint [1] 0 0
Baseline, Day 15
Primary outcome [2] 0 0
Change From Baseline In Plasma Intact C3 Level On Day 15
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
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
Timepoint [2] 0 0
Baseline, Day 15
Secondary outcome [3] 0 0
Time To Achieving Peak Serum C3 Levels
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
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)
Timepoint [5] 0 0
Days 1 and 7
Secondary outcome [6] 0 0
PK: Maximum Plasma Concentration (Cmax)
Timepoint [6] 0 0
Days 1 and 7
Secondary outcome [7] 0 0
PK: Time To Maximum Concentration (Tmax)
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
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
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.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Achillion, a wholly owned subsidiary of Alexion
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

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