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Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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ClinicalTrials.gov Identifier: NCT03053102
Recruitment Status : Completed
First Posted : February 14, 2017
Results First Posted : June 2, 2021
Last Update Posted : June 2, 2021
Sponsor:
Collaborator:
Achillion, a wholly owned subsidiary of Alexion
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention Drug: Danicopan
Enrollment 10
Recruitment Details  
Pre-assignment Details 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).
Arm/Group Title Danicopan
Hide Arm/Group Description Participants received danicopan 100 to 200 mg TID.
Period Title: Study Part 1: 28-Day Treatment
Started 10
Received at Least 1 Dose of Study Drug 10
Completed 10
Not Completed 0
Period Title: Study Part 2: 84-Day Treatment
Started 10
Completed 8
Not Completed 2
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             1
Arm/Group Title Danicopan
Hide Arm/Group Description Participants received danicopan 100 to 200 mg TID.
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
All participants who were enrolled in the study and received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
35.94  (13.575)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
5
  50.0%
Male
5
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
10
 100.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
White
7
  70.0%
Asian
1
  10.0%
Native Hawaiian or Other Pacific Islander
1
  10.0%
Other
1
  10.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants
New Zealand 6
South Korea 1
United Kingdom 1
Italy 2
1.Primary Outcome
Title Change From Baseline In Serum LDH Levels At Day 28
Hide Description Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.
Time Frame Baseline, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: IU/L
Baseline 1416  (540.25)
Day 28 (Part 1) 444.3  (255.78)
Change from Baseline -971.7  (549.76)
2.Secondary Outcome
Title Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Hide Description Change from Baseline = Hgb levels on Days 28 or 84 - Baseline Hgb levels.
Time Frame Baseline, Days 28 and 84
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: g/dL
Baseline Number Analyzed 10 participants
9.76  (1.758)
Part 1: Day 28 Number Analyzed 10 participants
10.94  (1.651)
Part 1: Change from Baseline at Day 28 Number Analyzed 10 participants
1.18  (0.877)
Part 2: Day 84 Number Analyzed 8 participants
11.45  (1.414)
Part 2: Change from Baseline at Day 84 Number Analyzed 8 participants
1.80  (1.166)
3.Secondary Outcome
Title Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
Hide 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 After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
SAE
1
  10.0%
TEAE Grade 3
1
  10.0%
TEAE Grade 4
1
  10.0%
AE leading to discontinuation
1
  10.0%
4.Secondary Outcome
Title Grade 3 And Grade 4 Laboratory Abnormalities
Hide Description Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE.
Time Frame After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine aminotransferase
1
  10.0%
Aspartate aminotransferase
1
  10.0%
Hemoglobin
1
  10.0%
Neutrophils
4
  40.0%
5.Secondary Outcome
Title Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
Hide Description Serial blood samples were collected predose and up to 8 hours postdose.
Time Frame Days 6 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
Day 6: 100 mg TID Number Analyzed 2 participants
1432.6
(19.41%)
Day 20: 150 mg TID Number Analyzed 4 participants
2370.4
(14.92%)
Day 20: 175 mg TID Number Analyzed 6 participants
2278.0
(37.30%)
6.Secondary Outcome
Title PK: Maximum Plasma Concentration (Cmax)
Hide Description Serial blood samples were collected predose and up to 12 hours postdose.
Time Frame Days 6 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Day 6: 100 mg TID Number Analyzed 2 participants
347.7
(9.57%)
Day 20: 150 mg TID Number Analyzed 4 participants
583.6
(27.29%)
Day 20: 175 mg TID Number Analyzed 6 participants
516.8
(33.39%)
7.Secondary Outcome
Title PK: Time To Maximum Concentration (Tmax)
Hide Description Serial blood samples were collected predose and up to 12 hours postdose.
Time Frame Days 6 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants who received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: hr
Day 6: 100 mg TID Number Analyzed 2 participants
4.17
(3.67 to 4.67)
Day 20: 150 mg TID Number Analyzed 4 participants
3.67
(1.05 to 4.67)
Day 20: 175 mg TID Number Analyzed 6 participants
4.11
(1.67 to 4.65)
8.Secondary Outcome
Title Complement Alternative Pathway (AP) Functional Activity
Hide Description Serum AP functional activity was measured by the Wieslab functional immunoassay method.
Time Frame Baseline and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: percentage of activity
Baseline 65.2  (13.71)
Day 28 12.7  (14.37)
9.Secondary Outcome
Title Complement Bb
Hide Description Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA).
Time Frame Baseline and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified.
Arm/Group Title Danicopan
Hide Arm/Group Description:
Participants received danicopan 100 to 200 mg TID.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: ug/mL
Baseline 2.24  (0.774)
Day 28 0.84  (0.838)
Time Frame After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
Adverse Event Reporting Description [Not specified]
 
Arm/Group Title Danicopan
Hide Arm/Group Description Participants received danicopan 100 to 200 mg TID.
All-Cause Mortality
Danicopan
Affected / at Risk (%)
Total   0/10 (0.00%) 
Hide Serious Adverse Events
Danicopan
Affected / at Risk (%)
Total   1/10 (10.00%) 
Blood and lymphatic system disorders   
Haemolysis  1  1/10 (10.00%) 
Investigations   
Alanine aminotransferase increased  1  1/10 (10.00%) 
Aspartate aminotransferase increased  1  1/10 (10.00%) 
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Danicopan
Affected / at Risk (%)
Total   9/10 (90.00%) 
Blood and lymphatic system disorders   
Paroxysmal nocturnal haemoglobinuria  1  1/10 (10.00%) 
Haemolysis  1  2/10 (20.00%) 
Gastrointestinal disorders   
Mouth ulceration  1  1/10 (10.00%) 
Nausea  1  1/10 (10.00%) 
Abdominal pain  1  1/10 (10.00%) 
Vomiting  1  1/10 (10.00%) 
General disorders   
Non-cardiac chest pain  1  1/10 (10.00%) 
Fatigue  1  1/10 (10.00%) 
Oedema peripheral  1  1/10 (10.00%) 
Vaccination site erythema  1  1/10 (10.00%) 
Infections and infestations   
Viral upper respiratory tract infection  1  1/10 (10.00%) 
Upper respiratory tract infection  1  4/10 (40.00%) 
Pharyngitis  1  1/10 (10.00%) 
Injury, poisoning and procedural complications   
Contusion  1  1/10 (10.00%) 
Investigations   
Alanine aminotransferase increased  1  1/10 (10.00%) 
Metabolism and nutrition disorders   
Iron deficiency  1  1/10 (10.00%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  2/10 (20.00%) 
Myalgia  1  1/10 (10.00%) 
Nervous system disorders   
Headache  1  4/10 (40.00%) 
Psychiatric disorders   
Irritability  1  1/10 (10.00%) 
Renal and urinary disorders   
Haemoglobinuria  1  2/10 (20.00%) 
Reproductive system and breast disorders   
Dysmenorrhoea  1  1/5 (20.00%) 
Skin and subcutaneous tissue disorders   
Rash papular  1  1/10 (10.00%) 
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Alexion Pharmaceuticals Inc.
Organization: Alexion Pharmaceuticals Inc.
Phone: 855-752-2356
EMail: clinicaltrials@alexion.com
Layout table for additonal information
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03053102    
Other Study ID Numbers: ACH471-100
2016-002652-25 ( EudraCT Number )
U1111-1190-3490 ( Other Identifier: UTN )
First Submitted: February 1, 2017
First Posted: February 14, 2017
Results First Submitted: May 7, 2021
Results First Posted: June 2, 2021
Last Update Posted: June 2, 2021