Trial Outcomes & Findings for Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab (NCT NCT03472885)

NCT ID: NCT03472885

Last Updated: 2023-12-12

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2023-12-12

Participant Flow

The study included a 24-Week Treatment Period and Long-term Extension (LTE) Period.

Participant milestones

Participant milestones
Measure	Danicopan + Eculizumab Participants were administered 100, 150, or 200 milligrams (mg) danicopan three times daily (TID) in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy. After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
24-Week Treatment Period STARTED	12
24-Week Treatment Period Safety Population: Received at Least 1 Dose of Study Drug	12
24-Week Treatment Period Efficacy Population: Received Study Drug for at Least 4 Weeks	11
24-Week Treatment Period COMPLETED	11
24-Week Treatment Period NOT COMPLETED	1
LTE Period (Maximum Exposure: 1463 Days) STARTED	11
LTE Period (Maximum Exposure: 1463 Days) COMPLETED	11
LTE Period (Maximum Exposure: 1463 Days) NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Danicopan + Eculizumab Participants were administered 100, 150, or 200 milligrams (mg) danicopan three times daily (TID) in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy. After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
24-Week Treatment Period Adverse Event	1

Baseline Characteristics

Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Danicopan + Eculizumab n=12 Participants Participants were administered 100, 150, or 200 mg danicopan TID in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy. After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
Age, Continuous	45.59 years STANDARD_DEVIATION 16.385 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Efficacy Population: All treated participants who received at least 4 weeks of danicopan.

Outcome measures

Outcome measures
Measure	Danicopan + Eculizumab n=11 Participants Participants were administered 100, 150, or 200 mg danicopan TID in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy. After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.	LTE Period: Danicopan + Eculizumab After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
Change From Baseline In Hemoglobin At Week 24 Baseline	7.94 g/dL Standard Deviation 1.425	—
Change From Baseline In Hemoglobin At Week 24 Week 24	10.33 g/dL Standard Deviation 1.661	—
Change From Baseline In Hemoglobin At Week 24 Change from Baseline	2.39 g/dL Standard Deviation 1.333	—

SECONDARY outcome

Timeframe: Within 24 weeks prior to first dose and during 24-week treatment period

Population: Efficacy Population: All treated participants who received at least 4 weeks of danicopan.

Outcome measures

Outcome measures
Measure	Danicopan + Eculizumab n=11 Participants Participants were administered 100, 150, or 200 mg danicopan TID in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy. After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.	LTE Period: Danicopan + Eculizumab After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment During 24-Week Treatment Period	0.2 RBC units Standard Deviation 0.60	—
Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment Within 24 Weeks Prior to First Dose	4.5 RBC units Standard Deviation 3.96	—

SECONDARY outcome

Timeframe: Within 24 weeks prior to first dose and during 24-week treatment period

Population: Efficacy Population: All treated participants who received at least 4 weeks of danicopan.

Outcome measures

Outcome measures
Measure	Danicopan + Eculizumab n=11 Participants Participants were administered 100, 150, or 200 mg danicopan TID in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy. After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.	LTE Period: Danicopan + Eculizumab After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment Within 24 Weeks Prior to First Dose	1 Participants	—
Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment During 24-Week Treatment Period	10 Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Efficacy Population: All treated participants who received at least 4 weeks of danicopan.

Outcome measures

Outcome measures
Measure	Danicopan + Eculizumab n=11 Participants Participants were administered 100, 150, or 200 mg danicopan TID in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy. After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.	LTE Period: Danicopan + Eculizumab After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
Change From Baseline In Lactate Dehydrogenase At Week 24 Baseline	244.5 IU/L Standard Deviation 74.40	—
Change From Baseline In Lactate Dehydrogenase At Week 24 Week 24	239.5 IU/L Standard Deviation 48.48	—
Change From Baseline In Lactate Dehydrogenase At Week 24 Change from Baseline	-5.0 IU/L Standard Deviation 48.60	—

SECONDARY outcome

Timeframe: Day 1 (after dosing) through end of study (maximum exposure: 1631 days)

Population: Participants who received at least 1 dose of danicopan were included in the safety assessment.

An AE was defined 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	Danicopan + Eculizumab n=12 Participants Participants were administered 100, 150, or 200 mg danicopan TID in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy. After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.	LTE Period: Danicopan + Eculizumab n=11 Participants After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug Grade 4 AEs	1 Participants	1 Participants
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug AEs Leading to Discontinuation of Study Drug	1 Participants	0 Participants
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug SAEs	2 Participants	7 Participants
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug Grade 3 AEs	4 Participants	6 Participants

Adverse Events

24-Week Treatment Period: Danicopan + Eculizumab

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

LTE Period: Danicopan + Eculizumab

Serious events: 7 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	24-Week Treatment Period: Danicopan + Eculizumab n=12 participants at risk Participants were administered 100, 150, or 200 mg danicopan TID in combination with eculizumab for 24 weeks. Danicopan dose may have been increased within each participant, to a maximum of 200 mg TID based on safety and efficacy.	LTE Period: Danicopan + Eculizumab n=11 participants at risk After completing the 24-Week Treatment Period, participants who received clinical benefit (as assessed by the Investigator based on improvement in hemoglobin) continued into the LTE and received the same dose of danicopan plus eculizumab treatment as that received at the end of the 24-Week Treatment Period.
Infections and infestations Pneumonia	8.3% 1/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	0.00% 0/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	8.3% 1/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	0.00% 0/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Infections and infestations Device related infection	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Infections and infestations Pyelonephritis	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Infections and infestations Tracheobronchitis viral	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
General disorders Influenza like illness	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
General disorders Pyrexia	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Blood and lymphatic system disorders Haemolysis	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Gastrointestinal disorders Pancreatitis	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Schwannoma	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.
Renal and urinary disorders Haemoglobinuria	0.00% 0/12 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.	9.1% 1/11 • Day 1 (after dosing) through end of study (maximum exposure: 1631 days) Participants who received at least 1 dose of danicopan were included in the safety assessment.

Other adverse events

Additional Information

Alexion Pharmaceuticals, Inc.

Phone: 855-752-2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place