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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-003525-42 | EudraCT Number |
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| Name | Class |
|---|---|
| Achillion, a wholly owned subsidiary of Alexion | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Experimental | All participants received 100 milligrams (mg) of danicopan three times per day (TID) during the Treatment Period. |
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| Group 2: Danicopan up to 200 mg TID | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Danicopan | Drug | Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period). |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels | Baseline, Day 15 |
| Change From Baseline In Plasma Intact C3 Level On Day 15 | 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 | Baseline, Day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | 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 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Melbourne | Australia | ||||
| Clinical Trial Site |
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Participants were recruited from 5 study centers total in Australia, Belgium, and The Netherlands. Only 3 study centers, 1 in each country, treated participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1: Danicopan 100 mg TID (Sentinel) | Participants received 100 milligrams (mg) of danicopan three times daily (TID) during the Treatment Period. |
| FG001 | Group 2: Danicopan up to 200 mg TID |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 9, 2017 | Jun 21, 2021 |
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| Baseline, Day 14 |
| Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | 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 | Baseline, Day 15 |
| Time To Achieving Peak Serum C3 Levels | Serial serum samples were collected on Days 1, 7, and 14. | From The First Day Of Dosing through Day 14 |
| 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 | 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. | Up to Day 49 |
| Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | 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. | Days 1 and 7 |
| PK: Maximum Plasma Concentration (Cmax) | 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. | Days 1 and 7 |
| PK: Time To Maximum Concentration (Tmax) | 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. | Days 1 and 7 |
| Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA). Change from Baseline = Complement Bb on Day 15 - Baseline | Baseline, Day 15 |
| Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Plasma sC5b-9 was measured by ELISA. Change from Baseline = sC5b-9 on Day 15 - Baseline sC5b-9 | Baseline, Day 15 |
| Antwerp |
| Belgium |
| Clinical Trial Site | Leiden | Netherlands |
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
| Received at Least 1 Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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All participants who received at least 1 dose of danicopan.
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1: Danicopan 100 mg TID (Sentinel) | Participants received 100 mg of danicopan TID during the Treatment Period. |
| BG001 | Group 2: Danicopan up to 200 mg TID | Participants received not more than 200 mg of danicopan TID during the Treatment Period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels | All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Mean | Standard Deviation | g/L | Baseline, Day 15 |
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| Primary | Change From Baseline In Plasma Intact C3 Level On Day 15 | 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 | All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Mean | Standard Deviation | μg/mL | Baseline, Day 15 |
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| Secondary | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | 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 | All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Mean | Standard Deviation | CAE unit | Baseline, Day 14 |
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| Secondary | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | 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 | All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Mean | Standard Deviation | percentage of activity | Baseline, Day 15 |
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| Secondary | Time To Achieving Peak Serum C3 Levels | Serial serum samples were collected on Days 1, 7, and 14. | All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Mean | Standard Deviation | days | From The First Day Of Dosing through Day 14 |
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| Secondary | 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 | 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. | All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Count of Participants | Participants | Up to Day 49 |
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| Secondary | Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | 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. | All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1 and 7 |
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| Secondary | PK: Maximum Plasma Concentration (Cmax) | 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. | All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1 and 7 |
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| Secondary | PK: Time To Maximum Concentration (Tmax) | 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. | All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Median | Full Range | hours | Days 1 and 7 |
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| Secondary | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA). Change from Baseline = Complement Bb on Day 15 - Baseline | All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Mean | Standard Deviation | µg/mL | Baseline, Day 15 |
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| Secondary | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Plasma sC5b-9 was measured by ELISA. Change from Baseline = sC5b-9 on Day 15 - Baseline sC5b-9 | All participants who received at least 1 dose of danicopan and who had a baseline measurement and at least 1 measurement during the treatment period. | Posted | Mean | Standard Deviation | ng/mL | Baseline, Day 15 |
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After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1: Danicopan 100 mg TID (Sentinel) | Participants received 100 mg of danicopan TID during the Treatment Period. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG001 | Group 2: Danicopan up to 200 mg TID | Participants received not more than 200 mg of danicopan TID during the Treatment Period. | 0 | 4 | 1 | 4 | 3 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Presyncope | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
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| Pain | General disorders | MedDRA (20.0) | Systematic Assessment |
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| Crepitations | General disorders | MedDRA (20.0) | Systematic Assessment |
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| Prerenal failure | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
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The sample size of the study was based on very limited clinical cases of C3G and IC-MPGN and the exploratory nature of this study to evaluate the effectiveness of danicopan.
Plasma intact C3 values should be regarded with caution. Plasma intact C3 values were generated using a new multiplex assay method with limited historical experience, and internal studies have suggested this new assay is subject to unexplained experimental variation arising during sample preparation and handling.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals Inc. | Alexion Pharmaceuticals Inc. | 855-752-2356 | clinicaltrials@alexion.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 2, 2019 | Jun 21, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015432 | Glomerulonephritis, Membranoproliferative |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
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| C000718467 | danicopan |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Change from Baseline |
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| Units | Counts |
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| Participants |
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| OG002 | Total | All participants who received at least 1 dose of danicopan. |
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