Trial Outcomes & Findings for A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN (NCT NCT03124368)

NCT ID: NCT03124368

Last Updated: 2021-11-04

Results Overview

Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Baseline, Day 15

Results posted on

2021-11-04

Participant Flow

Participants were recruited from 5 study centers total in Australia, Belgium, and The Netherlands. Only 3 study centers, 1 in each country, treated participants.

Participant milestones

Participant milestones
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
Participants received 100 milligrams (mg) of danicopan three times daily (TID) during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Overall Study
STARTED
2
4
Overall Study
Received at Least 1 Dose of Study Drug
2
4
Overall Study
COMPLETED
2
4
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
Total of all reporting groups
Age, Continuous
25.50 years
STANDARD_DEVIATION 7.85 • n=5 Participants
30.00 years
STANDARD_DEVIATION 12.68 • n=7 Participants
28.50 years
STANDARD_DEVIATION 10.69 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
0 Participants
n=5 Participants
3 Participants
n=7 Participants
3 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
All participants who received at least 1 dose of danicopan.
Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
Baseline
0.32 g/L
Standard Deviation 0.060
0.56 g/L
Standard Deviation 0.230
0.48 g/L
Standard Deviation 0.220
Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
Day 15
0.35 g/L
Standard Deviation 0.060
0.70 g/L
Standard Deviation 0.350
0.58 g/L
Standard Deviation 0.330
Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
Change from Baseline
0.03 g/L
Standard Deviation 0.000
0.14 g/L
Standard Deviation 0.140
0.11 g/L
Standard Deviation 0.120

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
All participants who received at least 1 dose of danicopan.
Change From Baseline In Plasma Intact C3 Level On Day 15
Baseline
39.50 μg/mL
Standard Deviation 0.710
58.25 μg/mL
Standard Deviation 47.910
52.00 μg/mL
Standard Deviation 38.360
Change From Baseline In Plasma Intact C3 Level On Day 15
Day 15
54.30 μg/mL
Standard Deviation 17.390
33.50 μg/mL
Standard Deviation 9.040
40.43 μg/mL
Standard Deviation 15.000
Change From Baseline In Plasma Intact C3 Level On Day 15
Change from Baseline
14.80 μg/mL
Standard Deviation 18.100
-24.75 μg/mL
Standard Deviation 50.970
-11.57 μg/mL
Standard Deviation 45.180

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
All participants who received at least 1 dose of danicopan.
Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14
Day 14
41.50 CAE unit
Standard Deviation 23.330
96.75 CAE unit
Standard Deviation 23.680
78.33 CAE unit
Standard Deviation 35.490
Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14
Change from Baseline
10.50 CAE unit
Standard Deviation 2.120
5.75 CAE unit
Standard Deviation 34.250
7.33 CAE unit
Standard Deviation 26.660
Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14
Baseline
31.00 CAE unit
Standard Deviation 21.210
91.00 CAE unit
Standard Deviation 41.370
71.00 CAE unit
Standard Deviation 45.570

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
All participants who received at least 1 dose of danicopan.
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
0.993 percentage of activity
Standard Deviation 1.1101
1.207 percentage of activity
Standard Deviation 1.3852
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
31.073 percentage of activity
Standard Deviation 19.779
23.498 percentage of activity
Standard Deviation 19.862
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
-30.08 percentage of activity
Standard Deviation 19.176
-22.29 percentage of activity
Standard Deviation 19.484

SECONDARY outcome

Timeframe: 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.

Serial serum samples were collected on Days 1, 7, and 14.

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
All participants who received at least 1 dose of danicopan.
Time To Achieving Peak Serum C3 Levels
2.5 days
Standard Deviation 2.12
10.5 days
Standard Deviation 4.43
7.8 days
Standard Deviation 5.46

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
All participants who received at least 1 dose of danicopan.
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
3 Participants
5 Participants
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
1 Participants
1 Participants
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
0 Participants
0 Participants
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
0 Participants
0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=1 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=3 Participants
All participants who received at least 1 dose of danicopan.
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
2060 h*ng/mL
1640 h*ng/mL
Geometric Coefficient of Variation 42.8
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
2470 h*ng/mL
1760 h*ng/mL
Geometric Coefficient of Variation 24.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=1 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=3 Participants
All participants who received at least 1 dose of danicopan.
PK: Maximum Plasma Concentration (Cmax)
Day 1
199 ng/mL
Geometric Coefficient of Variation 6.75
563 ng/mL
427 ng/mL
Geometric Coefficient of Variation 46.3
PK: Maximum Plasma Concentration (Cmax)
Day 7
270 ng/mL
Geometric Coefficient of Variation 41.2
579 ng/mL
385 ng/mL
Geometric Coefficient of Variation 39.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=1 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=3 Participants
All participants who received at least 1 dose of danicopan.
PK: Time To Maximum Concentration (Tmax)
Day 1
1.00 hours
Interval 1.0 to 1.0
2.50 hours
Interval 2.5 to 2.5
2.00 hours
Interval 1.5 to 2.0
PK: Time To Maximum Concentration (Tmax)
Day 7
2.75 hours
Interval 1.5 to 4.0
2.50 hours
Interval 2.5 to 2.5
1.50 hours
Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: 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.

Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA). Change from Baseline = Complement Bb on Day 15 - Baseline

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
All participants who received at least 1 dose of danicopan.
Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15
Baseline
1.789 µg/mL
Standard Deviation 1.2116
1.229 µg/mL
Standard Deviation 0.4729
1.416 µg/mL
Standard Deviation 0.7152
Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15
Day 15
1.511 µg/mL
Standard Deviation 0.9781
0.622 µg/mL
Standard Deviation 0.3349
0.918 µg/mL
Standard Deviation 0.6854
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
-0.607 µg/mL
Standard Deviation 0.1790
-0.497 µg/mL
Standard Deviation 0.2430

SECONDARY outcome

Timeframe: 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.

Plasma sC5b-9 was measured by ELISA. Change from Baseline = sC5b-9 on Day 15 - Baseline sC5b-9

Outcome measures

Outcome measures
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 Participants
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 Participants
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Total
n=6 Participants
All participants who received at least 1 dose of danicopan.
Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15
Baseline
1002.0 ng/mL
Standard Deviation 684.4794
613.750 ng/mL
Standard Deviation 225.2397
743.167 ng/mL
Standard Deviation 405.3874
Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15
Day 15
1105.5 ng/mL
Standard Deviation 622.9611
563.850 ng/mL
Standard Deviation 302.4446
744.400 ng/mL
Standard Deviation 459.0596
Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15
Change from Baseline
103.500 ng/mL
Standard Deviation 61.5183
-49.900 ng/mL
Standard Deviation 237.1917
1.233 ng/mL
Standard Deviation 201.9602

Adverse Events

Group 1: Danicopan 100 mg TID (Sentinel)

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Group 2: Danicopan up to 200 mg TID

Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 participants at risk
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 participants at risk
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Nervous system disorders
Presyncope
0.00%
0/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
25.0%
1/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]

Other adverse events

Other adverse events
Measure
Group 1: Danicopan 100 mg TID (Sentinel)
n=2 participants at risk
Participants received 100 mg of danicopan TID during the Treatment Period.
Group 2: Danicopan up to 200 mg TID
n=4 participants at risk
Participants received not more than 200 mg of danicopan TID during the Treatment Period.
Blood and lymphatic system disorders
Anaemia
50.0%
1/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
25.0%
1/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
Nervous system disorders
Dizziness
50.0%
1/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
0.00%
0/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
Infections and infestations
Upper respiratory tract infection
50.0%
1/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
0.00%
0/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
Metabolism and nutrition disorders
Hypokalaemia
50.0%
1/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
0.00%
0/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
Gastrointestinal disorders
Diarrhoea
50.0%
1/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
0.00%
0/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
Vascular disorders
Hypotension
0.00%
0/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
25.0%
1/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
Nervous system disorders
Headache
0.00%
0/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
25.0%
1/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
General disorders
Pain
0.00%
0/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
25.0%
1/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
General disorders
Crepitations
0.00%
0/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
25.0%
1/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
Renal and urinary disorders
Prerenal failure
0.00%
0/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
25.0%
1/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
Metabolism and nutrition disorders
Hyperkalaemia
0.00%
0/2 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]
25.0%
1/4 • After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
\[Not specified\]

Additional Information

Alexion Pharmaceuticals Inc.

Alexion Pharmaceuticals Inc.

Phone: 855-752-2356

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place