Trial Outcomes & Findings for Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) (NCT NCT03053102)
NCT ID: NCT03053102
Last Updated: 2022-06-23
Results Overview
Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.
COMPLETED
PHASE2
10 participants
Baseline, Day 28
2022-06-23
Participant Flow
The study was conducted in 2 parts. In Part 1, participants received danicopan for 28 days. Starting doses were 100 or 150 milligrams (mg) three times daily (TID). A further dose increase up to 175 mg TID (N=8 participants) and 200 mg TID (N=4 participants) was conducted. Participants with reductions in lactate dehydrogenase (LDH) meeting specified criteria were offered continued dosing beyond Day 28, for up to 8 additional weeks (Part 2).
Participant milestones
| Measure |
Danicopan
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Study Part 1: 28-Day Treatment
STARTED
|
10
|
|
Study Part 1: 28-Day Treatment
Received at Least 1 Dose of Study Drug
|
10
|
|
Study Part 1: 28-Day Treatment
COMPLETED
|
10
|
|
Study Part 1: 28-Day Treatment
NOT COMPLETED
|
0
|
|
Study Part 2: 84-Day Treatment
STARTED
|
10
|
|
Study Part 2: 84-Day Treatment
COMPLETED
|
8
|
|
Study Part 2: 84-Day Treatment
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Danicopan
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Study Part 2: 84-Day Treatment
Adverse Event
|
1
|
|
Study Part 2: 84-Day Treatment
Withdrawal by Subject
|
1
|
Baseline Characteristics
Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Baseline characteristics by cohort
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Age, Continuous
|
35.94 years
STANDARD_DEVIATION 13.575 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 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
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
6 participants
n=5 Participants
|
|
Region of Enrollment
South Korea
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 28Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Change From Baseline In Serum LDH Levels At Day 28
Baseline
|
1416 international units per liter (IU/L)
Standard Deviation 540.25
|
|
Change From Baseline In Serum LDH Levels At Day 28
Day 28 (Part 1)
|
444.3 international units per liter (IU/L)
Standard Deviation 255.78
|
|
Change From Baseline In Serum LDH Levels At Day 28
Change from Baseline
|
-971.7 international units per liter (IU/L)
Standard Deviation 549.76
|
SECONDARY outcome
Timeframe: Baseline, Days 28 and 84Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Change from Baseline = Hgb levels on Days 28 or 84 - Baseline Hgb levels.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Baseline
|
9.76 grams/deciliter (g/dL)
Standard Deviation 1.758
|
|
Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Part 1: Day 28
|
10.94 grams/deciliter (g/dL)
Standard Deviation 1.651
|
|
Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Part 1: Change from Baseline at Day 28
|
1.18 grams/deciliter (g/dL)
Standard Deviation 0.877
|
|
Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Part 2: Day 84
|
11.45 grams/deciliter (g/dL)
Standard Deviation 1.414
|
|
Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Part 2: Change from Baseline at Day 84
|
1.80 grams/deciliter (g/dL)
Standard Deviation 1.166
|
SECONDARY outcome
Timeframe: Baseline, Day 84Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Change from Baseline = Serum LDH levels on Day 84 - Baseline Serum LDH levels.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Change From Baseline In Serum LDH Levels At Day 84
Baseline
|
1416 IU/L
Standard Deviation 540.25
|
|
Change From Baseline In Serum LDH Levels At Day 84
Day 84 (Part 2)
|
537.3 IU/L
Standard Deviation 260.42
|
|
Change From Baseline In Serum LDH Levels At Day 84
Change from Baseline
|
-865.9 IU/L
Standard Deviation 447.86
|
SECONDARY outcome
Timeframe: Baseline, Day 28, and Day 84Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
PNH RBC, summed type III, clone size levels were assessed from Baseline to Day 28 and Day 84. The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size
Baseline
|
31.5363 percentage of the total cell population
Standard Deviation 24.62004
|
|
Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size
Day 28
|
43.6279 percentage of the total cell population
Standard Deviation 15.58021
|
|
Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size
Day 84
|
56.2953 percentage of the total cell population
Standard Deviation 19.85086
|
SECONDARY outcome
Timeframe: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)Population: All participants who received at least 1 dose of study drug.
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
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
SAE
|
1 Participants
|
|
Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
TEAE Grade 3
|
1 Participants
|
|
Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
TEAE Grade 4
|
1 Participants
|
|
Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
AE leading to discontinuation
|
1 Participants
|
SECONDARY outcome
Timeframe: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).Population: All participants who received at least 1 dose of study drug.
Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Grade 3 And Grade 4 Laboratory Abnormalities
Alanine aminotransferase increased
|
1 Participants
|
|
Grade 3 And Grade 4 Laboratory Abnormalities
Aspartate aminotransferase increased
|
1 Participants
|
|
Grade 3 And Grade 4 Laboratory Abnormalities
Low hemoglobin
|
1 Participants
|
|
Grade 3 And Grade 4 Laboratory Abnormalities
Low neutrophil count
|
4 Participants
|
|
Grade 3 And Grade 4 Laboratory Abnormalities
High triglycerides
|
1 Participants
|
SECONDARY outcome
Timeframe: Days 6 and 20Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. PK analysis was not conducted on the 200 mg dose.
Serial blood samples were collected predose and up to 8 hours postdose.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
Day 6: 100 mg TID
|
1432.611 hour (hr)*nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 19.41
|
|
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
Day 20: 150 mg TID
|
2370.421 hour (hr)*nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 14.92
|
|
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
Day 20: 175 mg TID
|
2278.038 hour (hr)*nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 37.30
|
SECONDARY outcome
Timeframe: Days 6 and 20Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. PK analysis was not conducted on the 200 mg dose.
Serial blood samples were collected predose and up to 12 hours postdose.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
PK: Maximum Plasma Concentration (Cmax)
Day 6: 100 mg TID
|
347.707 ng/mL
Geometric Coefficient of Variation 9.57
|
|
PK: Maximum Plasma Concentration (Cmax)
Day 20: 150 mg TID
|
583.626 ng/mL
Geometric Coefficient of Variation 27.29
|
|
PK: Maximum Plasma Concentration (Cmax)
Day 20: 175 mg TID
|
516.8788 ng/mL
Geometric Coefficient of Variation 33.39
|
SECONDARY outcome
Timeframe: Days 6 and 20Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. PK analysis was not conducted on the 200 mg dose.
Serial blood samples were collected predose and up to 12 hours postdose.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
PK: Time To Maximum Concentration (Tmax)
Day 6: 100 mg TID
|
4.17 hr
Interval 3.67 to 4.67
|
|
PK: Time To Maximum Concentration (Tmax)
Day 20: 150 mg TID
|
3.67 hr
Interval 1.05 to 4.67
|
|
PK: Time To Maximum Concentration (Tmax)
Day 20: 175 mg TID
|
4.11 hr
Interval 1.67 to 4.65
|
SECONDARY outcome
Timeframe: Baseline and Day 28Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Serum AP functional activity was measured by the Wieslab functional immunoassay method.
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Complement Alternative Pathway (AP) Functional Activity
Baseline
|
65.216 percentage of activity
Standard Deviation 13.7143
|
|
Complement Alternative Pathway (AP) Functional Activity
Day 28
|
12.730 percentage of activity
Standard Deviation 14.37670
|
SECONDARY outcome
Timeframe: Baseline and Day 28Population: All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA).
Outcome measures
| Measure |
Danicopan
n=10 Participants
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Complement Bb
Baseline
|
2.24160 microgram (ug)/mL
Standard Deviation 0.773962
|
|
Complement Bb
Day 28
|
0.83913 microgram (ug)/mL
Standard Deviation 0.838219
|
Adverse Events
Danicopan
Serious adverse events
| Measure |
Danicopan
n=10 participants at risk
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Blood and lymphatic system disorders
Haemolysis
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Investigations
Aspartate aminotransferase increased
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
Other adverse events
| Measure |
Danicopan
n=10 participants at risk
Participants received danicopan 100 to 200 mg TID.
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
2/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
General disorders
Non-cardiac chest pain
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Nervous system disorders
Headache
|
40.0%
4/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Infections and infestations
Viral upper respiratory tract infection
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Infections and infestations
Upper respiratory tract infection
|
40.0%
4/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
General disorders
Fatigue
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Psychiatric disorders
Irritability
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Metabolism and nutrition disorders
Iron deficiency
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Gastrointestinal disorders
Mouth ulceration
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
General disorders
Oedema peripheral
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
General disorders
Vaccination site erythema
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Blood and lymphatic system disorders
Paroxysmal nocturnal haemoglobinuria
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
20.0%
1/5 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Renal and urinary disorders
Haemoglobinuria
|
20.0%
2/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Blood and lymphatic system disorders
Haemolysis
|
20.0%
2/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Injury, poisoning and procedural complications
Contusion
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Infections and infestations
Pharyngitis
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
1/10 • After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
\[Not specified\]
|
Additional Information
Alexion Pharmaceuticals Inc.
Alexion Pharmaceuticals Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place