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

• Sponsor: Alexion Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03124368
• Collaborator: Achillion, a wholly owned subsidiary of Alexion (Industry)
• Enrollment: 6
• Locations: 3
• Arms: 2
• Actual Duration (Months): 17
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
C3 Glomerulonephritis; Dense Deposit Disease; C3 Glomerulopathy; Immune Complex Mediated Membranoproliferative Glomerulonephritis; Membranoproliferative Glomerulonephritis Types I, II, and III	Drug: Danicopan	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official 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)
• Actual Study Start Date: Aug 9, 2017
• Actual Primary Completion Date: Dec 21, 2018
• Actual Study Completion Date: Jan 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Danicopan; Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).; Other Names: ACH-4471 ACH4471 4471 ACH-0144471 ALXN2040
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.	Drug: Danicopan; Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).; Other Names: ACH-4471 ACH4471 4471 ACH-0144471 ALXN2040

Outcome Measures

Primary Outcome Measures

1. 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

2. 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 Outcome Measures

1. 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

2. 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

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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

9. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Melbourne		Australia
2	Clinical Trial Site	Antwerpen		Belgium
3	Clinical Trial Site	Leiden		Netherlands

Sponsors and Collaborators

• Alexion Pharmaceuticals
• Achillion, a wholly owned subsidiary of Alexion

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 9, 2017
• Statistical Analysis Plan - Jan 2, 2019

More Information

Publications

None provided.

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03124368
• Other Study ID Numbers: ACH471-201; 2016-003525-42
• First Posted: Apr 21, 2017
• Last Update Posted: Nov 4, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Alexion Pharmaceuticals: 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
• Additional relevant MeSH terms: Glomerulonephritis; Glomerulonephritis, Membranoproliferative

Study Results

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.

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

Baseline Characteristics

Arm/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	Total of all reporting groups
Overall Participants	2	4	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.50 (7.85)	30.00 (12.68)	28.50 (10.69)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 25%	1 16.7%
Male	2 100%	3 75%	5 83.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 100%	1 25%	3 50%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	3 75%	3 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	All participants who received at least 1 dose of danicopan.
Measure Participants	2	4	6
Baseline	0.32 (0.060)	0.56 (0.230)	0.48 (0.220)
Day 15	0.35 (0.060)	0.70 (0.350)	0.58 (0.330)
Change from Baseline	0.03 (0.000)	0.14 (0.140)	0.11 (0.120)

2. Primary Outcome

Title	Change From Baseline In Plasma Intact C3 Level On Day 15
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	All participants who received at least 1 dose of danicopan.
Measure Participants	2	4	6
Baseline	39.50 (0.710)	58.25 (47.910)	52.00 (38.360)
Day 15	54.30 (17.390)	33.50 (9.040)	40.43 (15.000)
Change from Baseline	14.80 (18.100)	-24.75 (50.970)	-11.57 (45.180)

3. Secondary Outcome

Title	Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	All participants who received at least 1 dose of Danicopan.
Measure Participants	2	4	6
Baseline	31.00 (21.210)	91.00 (41.370)	71.00 (45.570)
Day 14	41.50 (23.330)	96.75 (23.680)	78.33 (35.490)
Change from Baseline	10.50 (2.120)	5.75 (34.250)	7.33 (26.660)

4. Secondary Outcome

Title	Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	All participants who received at least 1 dose of danicopan.
Measure Participants	2	4	6
Baseline	8.350 (10.508)	31.073 (19.779)	23.498 (19.862)
Day 15	1.635 (2.3122)	0.993 (1.1101)	1.207 (1.3852)
Change from Baseline	-6.715 (8.1954)	-30.08 (19.176)	-22.29 (19.484)

5. Secondary Outcome

Title	Time To Achieving Peak Serum C3 Levels
Description	Serial serum samples were collected on Days 1, 7, and 14.
Time Frame	From The First Day Of Dosing through Day 14

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	All participants who received at least 1 dose of danicopan.
Measure Participants	2	4	6
Mean (Standard Deviation) [days]	2.5 (2.12)	10.5 (4.43)	7.8 (5.46)

6. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	All participants who received at least 1 dose of danicopan.
Measure Participants	2	4	6
TEAEs	2 100%	3 75%	5 83.3%
SAEs	0 0%	1 25%	1 16.7%
TEAEs ≥Grade 3	0 0%	0 0%	0 0%
TEAEs leading to discontinuation	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8)
Description	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

Outcome Measure Data

Analysis Population Description

All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period.

Arm/Group Title	Group 1: Danicopan 100 mg TID	Group 2: Danicopan 150 mg TID	Group 2: Danicopan 200 mg TID
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received 150 mg of danicopan TID during the Treatment Period.	Participants received 200 mg of danicopan TID during the Treatment Period.
Measure Participants	2	1	3
Day 1	871 (38.1)	2060	1640 (42.8)
Day 7	1120 (44.4)	2470	1760 (24.2)

8. Secondary Outcome

Title	PK: Maximum Plasma Concentration (Cmax)
Description	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

Outcome Measure Data

Analysis Population Description

All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period.

Arm/Group Title	Group 1: Danicopan 100 mg TID	Group 2: Danicopan 150 mg TID	Group 2: Danicopan 200 mg TID
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received 150 mg of danicopan TID during the Treatment Period.	Participants received 200 mg of danicopan TID during the Treatment Period.
Measure Participants	2	1	3
Day 1	199 (6.75)	563	427 (46.3)
Day 7	270 (41.2)	579	385 (39.1)

9. Secondary Outcome

Title	PK: Time To Maximum Concentration (Tmax)
Description	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

Outcome Measure Data

Analysis Population Description

All participants receiving at least 1 dose of danicopan who had a baseline measurement and at least 1 measurement during the treatment period.

Arm/Group Title	Group 1: Danicopan 100 mg TID	Group 2: Danicopan 150 mg TID	Group 2: Danicopan 200 mg TID
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received 150 mg of danicopan TID during the Treatment Period.	Participants received 200 mg of danicopan TID during the Treatment Period.
Measure Participants	2	1	3
Day 1	1.00	2.50	2.00
Day 7	2.75	2.50	1.50

10. Secondary Outcome

Title	Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15
Description	Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA). Change from Baseline = Complement Bb on Day 15 - Baseline
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	All participants who received at least 1 dose of danicopan.
Measure Participants	2	4	6
Baseline	1.789 (1.2116)	1.229 (0.4729)	1.416 (0.7152)
Day 15	1.511 (0.9781)	0.622 (0.3349)	0.918 (0.6854)
Change from baseline	-0.278 (0.2335)	-0.607 (0.1790)	-0.497 (0.2430)

11. Secondary Outcome

Title	Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15
Description	Plasma sC5b-9 was measured by ELISA. Change from Baseline = sC5b-9 on Day 15 - Baseline sC5b-9
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

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/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)	Group 2: Danicopan up to 200 mg TID	Total
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.	Participants received not more than 200 mg of danicopan TID during the Treatment Period.	All participants who received at least 1 dose of danicopan.
Measure Participants	2	4	6
Baseline	1002.0 (684.4794)	613.750 (225.2397)	743.167 (405.3874)
Day 15	1105.5 (622.9611)	563.850 (302.4446)	744.400 (459.0596)
Change from Baseline	103.500 (61.5183)	-49.900 (237.1917)	1.233 (201.9602)

Adverse Events

Time Frame	After the first dose of study medication (following Day 0) through the follow-up visit at Day 49.
Adverse Event Reporting Description	[Not specified]
Arm/Group Title	Group 1: Danicopan 100 mg TID (Sentinel)		Group 2: Danicopan up to 200 mg TID
Arm/Group Description	Participants received 100 mg of danicopan TID during the Treatment Period.		Participants received not more than 200 mg of danicopan TID during the Treatment Period.
All Cause Mortality
	Group 1: Danicopan 100 mg TID (Sentinel)		Group 2: Danicopan up to 200 mg TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)
Serious Adverse Events
	Group 1: Danicopan 100 mg TID (Sentinel)		Group 2: Danicopan up to 200 mg TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		1/4 (25%)
Nervous system disorders
Presyncope	0/2 (0%)		1/4 (25%)
Other (Not Including Serious) Adverse Events
	Group 1: Danicopan 100 mg TID (Sentinel)		Group 2: Danicopan up to 200 mg TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		3/4 (75%)
Blood and lymphatic system disorders
Anaemia	1/2 (50%)		1/4 (25%)
Gastrointestinal disorders
Diarrhoea	1/2 (50%)		0/4 (0%)
General disorders
Pain	0/2 (0%)		1/4 (25%)
Crepitations	0/2 (0%)		1/4 (25%)
Infections and infestations
Upper respiratory tract infection	1/2 (50%)		0/4 (0%)
Metabolism and nutrition disorders
Hypokalaemia	1/2 (50%)		0/4 (0%)
Hyperkalaemia	0/2 (0%)		1/4 (25%)
Nervous system disorders
Dizziness	1/2 (50%)		0/4 (0%)
Headache	0/2 (0%)		1/4 (25%)
Renal and urinary disorders
Prerenal failure	0/2 (0%)		1/4 (25%)
Vascular disorders
Hypotension	0/2 (0%)		1/4 (25%)

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.