C3 Glomerulonephritis, C3 Glomerulopathy, Dense Deposit Disease, Immune Complex Mediated Membranoproliferative Glomerulonephritis, Membranoproliferative Glomerulonephritis Types I, II, and III
Conditions
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
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.
Interventions
DRUGDanicopan
Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).
Sponsors
Achillion, a wholly owned subsidiary of Alexion
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Baseline, 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 |
| Change From Baseline In Plasma Intact C3 Level On Day 15 | Baseline, 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time To Achieving Peak Serum C3 Levels | From The First Day Of Dosing through Day 14 | Serial serum samples were collected on Days 1, 7, and 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 | Up to Day 49 | 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. |
| Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | Days 1 and 7 | 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. |
| Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Baseline, 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 |
| PK: Time To Maximum Concentration (Tmax) | Days 1 and 7 | 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. |
| Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Baseline, Day 15 | Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA). Change from Baseline = Complement Bb on Day 15 - Baseline |
| Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Baseline, Day 15 | Plasma sC5b-9 was measured by ELISA. Change from Baseline = sC5b-9 on Day 15 - Baseline sC5b-9 |
| PK: Maximum Plasma Concentration (Cmax) | Days 1 and 7 | 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. |
| Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Baseline, 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 |
Countries
Australia, Belgium, Netherlands
Participant flow
Recruitment details
Participants were recruited from 5 study centers total in Australia, Belgium, and The Netherlands. Only 3 study centers, 1 in each country, treated participants.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) Participants received 100 mg of danicopan TID during the Treatment Period. | 2 |
| Group 2: Danicopan up to 200 mg TID Participants received not more than 200 mg of danicopan TID during the Treatment Period. | 4 |
| Total | 6 |
Baseline characteristics
| Characteristic | Group 2: Danicopan up to 200 mg TID | Total | Group 1: Danicopan 100 mg TID (Sentinel) |
|---|---|---|---|
| Age, Continuous | 30.00 years STANDARD_DEVIATION 12.68 | 28.50 years STANDARD_DEVIATION 10.69 | 25.50 years STANDARD_DEVIATION 7.85 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 2 / 2 | 3 / 4 |
| serious Total, serious adverse events | 0 / 2 | 1 / 4 |
Outcome results
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
Time frame: Baseline, Day 15
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Plasma Intact C3 Level On Day 15 | Change from Baseline | 14.80 μg/mL | Standard Deviation 18.1 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Plasma Intact C3 Level On Day 15 | Day 15 | 54.30 μg/mL | Standard Deviation 17.39 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Plasma Intact C3 Level On Day 15 | Baseline | 39.50 μg/mL | Standard Deviation 0.71 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Plasma Intact C3 Level On Day 15 | Day 15 | 33.50 μg/mL | Standard Deviation 9.04 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Plasma Intact C3 Level On Day 15 | Baseline | 58.25 μg/mL | Standard Deviation 47.91 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Plasma Intact C3 Level On Day 15 | Change from Baseline | -24.75 μg/mL | Standard Deviation 50.97 |
| Total | Change From Baseline In Plasma Intact C3 Level On Day 15 | Baseline | 52.00 μg/mL | Standard Deviation 38.36 |
| Total | Change From Baseline In Plasma Intact C3 Level On Day 15 | Change from Baseline | -11.57 μg/mL | Standard Deviation 45.18 |
| Total | Change From Baseline In Plasma Intact C3 Level On Day 15 | Day 15 | 40.43 μg/mL | Standard Deviation 15 |
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
Time frame: Baseline, Day 15
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Day 15 | 0.35 g/L | Standard Deviation 0.06 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Baseline | 0.32 g/L | Standard Deviation 0.06 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Change from Baseline | 0.03 g/L | Standard Deviation 0 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Day 15 | 0.70 g/L | Standard Deviation 0.35 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Baseline | 0.56 g/L | Standard Deviation 0.23 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Change from Baseline | 0.14 g/L | Standard Deviation 0.14 |
| Total | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Baseline | 0.48 g/L | Standard Deviation 0.22 |
| Total | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Change from Baseline | 0.11 g/L | Standard Deviation 0.12 |
| Total | Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 | Day 15 | 0.58 g/L | Standard Deviation 0.33 |
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
Time frame: Baseline, Day 15
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Change from baseline | -0.278 µg/mL | Standard Deviation 0.2335 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Day 15 | 1.511 µg/mL | Standard Deviation 0.9781 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Baseline | 1.789 µg/mL | Standard Deviation 1.2116 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Day 15 | 0.622 µg/mL | Standard Deviation 0.3349 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Baseline | 1.229 µg/mL | Standard Deviation 0.4729 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Change from baseline | -0.607 µg/mL | Standard Deviation 0.179 |
| Total | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Baseline | 1.416 µg/mL | Standard Deviation 0.7152 |
| Total | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Change from baseline | -0.497 µg/mL | Standard Deviation 0.243 |
| Total | Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15 | Day 15 | 0.918 µg/mL | Standard Deviation 0.6854 |
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
Time frame: Baseline, Day 15
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Change from Baseline | 103.500 ng/mL | Standard Deviation 61.5183 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Baseline | 1002.0 ng/mL | Standard Deviation 684.4794 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Day 15 | 1105.5 ng/mL | Standard Deviation 622.9611 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Baseline | 613.750 ng/mL | Standard Deviation 225.2397 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Day 15 | 563.850 ng/mL | Standard Deviation 302.4446 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Change from Baseline | -49.900 ng/mL | Standard Deviation 237.1917 |
| Total | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Baseline | 743.167 ng/mL | Standard Deviation 405.3874 |
| Total | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Change from Baseline | 1.233 ng/mL | Standard Deviation 201.9602 |
| Total | Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15 | Day 15 | 744.400 ng/mL | Standard Deviation 459.0596 |
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
Time frame: Baseline, Day 15
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Day 15 | 1.635 percentage of activity | Standard Deviation 2.3122 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Baseline | 8.350 percentage of activity | Standard Deviation 10.508 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Change from Baseline | -6.715 percentage of activity | Standard Deviation 8.1954 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Day 15 | 0.993 percentage of activity | Standard Deviation 1.1101 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Baseline | 31.073 percentage of activity | Standard Deviation 19.779 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Change from Baseline | -30.08 percentage of activity | Standard Deviation 19.176 |
| Total | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Baseline | 23.498 percentage of activity | Standard Deviation 19.862 |
| Total | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Change from Baseline | -22.29 percentage of activity | Standard Deviation 19.484 |
| Total | Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15 | Day 15 | 1.207 percentage of activity | Standard Deviation 1.3852 |
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
Time frame: Baseline, Day 14
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Day 14 | 41.50 CAE unit | Standard Deviation 23.33 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Baseline | 31.00 CAE unit | Standard Deviation 21.21 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Change from Baseline | 10.50 CAE unit | Standard Deviation 2.12 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Day 14 | 96.75 CAE unit | Standard Deviation 23.68 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Baseline | 91.00 CAE unit | Standard Deviation 41.37 |
| Group 2: Danicopan up to 200 mg TID | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Change from Baseline | 5.75 CAE unit | Standard Deviation 34.25 |
| Total | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Baseline | 71.00 CAE unit | Standard Deviation 45.57 |
| Total | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Change from Baseline | 7.33 CAE unit | Standard Deviation 26.66 |
| Total | Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14 | Day 14 | 78.33 CAE unit | Standard Deviation 35.49 |
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | 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 | TEAEs | 2 Participants |
| Group 1: Danicopan 100 mg TID (Sentinel) | 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 | SAEs | 0 Participants |
| Group 1: Danicopan 100 mg TID (Sentinel) | 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 | TEAEs ≥Grade 3 | 0 Participants |
| Group 1: Danicopan 100 mg TID (Sentinel) | 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 | TEAEs leading to discontinuation | 0 Participants |
| Group 2: Danicopan up to 200 mg TID | 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 | TEAEs leading to discontinuation | 0 Participants |
| Group 2: Danicopan up to 200 mg TID | 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 | TEAEs | 3 Participants |
| Group 2: Danicopan up to 200 mg TID | 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 | TEAEs ≥Grade 3 | 0 Participants |
| Group 2: Danicopan up to 200 mg TID | 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 | SAEs | 1 Participants |
| Total | 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 | TEAEs leading to discontinuation | 0 Participants |
| Total | 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 | SAEs | 1 Participants |
| Total | 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 | TEAEs ≥Grade 3 | 0 Participants |
| Total | 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 | TEAEs | 5 Participants |
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.
Time frame: Days 1 and 7
Population: All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | Day 1 | 871 h*ng/mL | Geometric Coefficient of Variation 38.1 |
| Group 1: Danicopan 100 mg TID (Sentinel) | Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | Day 7 | 1120 h*ng/mL | Geometric Coefficient of Variation 44.4 |
| Group 2: Danicopan up to 200 mg TID | Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | Day 1 | 2060 h*ng/mL | — |
| Group 2: Danicopan up to 200 mg TID | Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | Day 7 | 2470 h*ng/mL | — |
| Total | Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | Day 1 | 1640 h*ng/mL | Geometric Coefficient of Variation 42.8 |
| Total | Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8) | Day 7 | 1760 h*ng/mL | Geometric Coefficient of Variation 24.2 |
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.
Time frame: Days 1 and 7
Population: All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | PK: Maximum Plasma Concentration (Cmax) | Day 1 | 199 ng/mL | Geometric Coefficient of Variation 6.75 |
| Group 1: Danicopan 100 mg TID (Sentinel) | PK: Maximum Plasma Concentration (Cmax) | Day 7 | 270 ng/mL | Geometric Coefficient of Variation 41.2 |
| Group 2: Danicopan up to 200 mg TID | PK: Maximum Plasma Concentration (Cmax) | Day 1 | 563 ng/mL | — |
| Group 2: Danicopan up to 200 mg TID | PK: Maximum Plasma Concentration (Cmax) | Day 7 | 579 ng/mL | — |
| Total | PK: Maximum Plasma Concentration (Cmax) | Day 1 | 427 ng/mL | Geometric Coefficient of Variation 46.3 |
| Total | PK: Maximum Plasma Concentration (Cmax) | Day 7 | 385 ng/mL | Geometric Coefficient of Variation 39.1 |
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.
Time frame: Days 1 and 7
Population: All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | PK: Time To Maximum Concentration (Tmax) | Day 1 | 1.00 hours |
| Group 1: Danicopan 100 mg TID (Sentinel) | PK: Time To Maximum Concentration (Tmax) | Day 7 | 2.75 hours |
| Group 2: Danicopan up to 200 mg TID | PK: Time To Maximum Concentration (Tmax) | Day 1 | 2.50 hours |
| Group 2: Danicopan up to 200 mg TID | PK: Time To Maximum Concentration (Tmax) | Day 7 | 2.50 hours |
| Total | PK: Time To Maximum Concentration (Tmax) | Day 1 | 2.00 hours |
| Total | PK: Time To Maximum Concentration (Tmax) | Day 7 | 1.50 hours |
Secondary
Time To Achieving Peak Serum C3 Levels
Serial serum samples were collected on Days 1, 7, and 14.
Time frame: From The First Day Of Dosing through Day 14
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Time To Achieving Peak Serum C3 Levels | 2.5 days | Standard Deviation 2.12 |
| Group 2: Danicopan up to 200 mg TID | Time To Achieving Peak Serum C3 Levels | 10.5 days | Standard Deviation 4.43 |
| Total | Time To Achieving Peak Serum C3 Levels | 7.8 days | Standard Deviation 5.46 |