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

Phase 2

Completed

Brief Summary: To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan dose may be increased within each participant, to a maximum of 200 milligrams (mg) three times daily (TID) based on safety and efficacy at protocol-specified time points.

Detailed Description: The purpose of this study is to determine the effectiveness of danicopan in improving anemia, as measured by increased blood hemoglobin, when given with eculizumab (a drug commonly used for treatment of PNH) for 24 weeks in participants with PNH.

The 24-week treatment period was followed by a long-term extension phase. In the extension phase, participants received the same danicopan dose plus eculizumab as they were receiving at the end of 24-week treatment phase.

Results are reported for the 24-week treatment period.

Recruitment & Eligibility

Inclusion Criteria

Diagnosed with PNH
Have received at least one red blood cell transfusion within last 12 weeks
Anemia with adequate reticulocytosis
Must be on a stable regimen of eculizumab
Platelet count ≥ 40,000/microliter without the need for platelet transfusions
Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae or willingness to receive vaccinations based on local guidelines
Willingness to receive antibiotic prophylaxis
Female participants must use highly effective birth control to prevent pregnancy during the clinical trial and for 30 days after their last dose of study drug
Male participants must use a highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 90 days after the last dose of study drug

Key

Exclusion Criteria

Current evidence of bone marrow failure or aplastic anemia requiring treatment
History of a major organ transplant or hematopoietic stem cell/marrow transplant
Received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater
Documented C5 complement protein mutations
Known or suspected complement deficiency
Contraindication to any of the required vaccinations
Active bacterial infection or clinically significant active viral infection, a body temperature >38°C, or other evidence of infection
History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
History of hypersensitivity reactions to commonly used antibacterial agents

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Arm && Interventions

Group	Intervention	Description
Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab	Danicopan	Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab.
Group 4: Optimal Dose of Danicopan TID + Eculizumab	Danicopan	Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab.
Group 1: 100 mg Danicopan TID + Eculizumab	Danicopan	Starting dose of 100 mg danicopan TID in combination with eculizumab.
Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab	Danicopan	Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab.
Group 4: Optimal Dose of Danicopan TID + Eculizumab	Eculizumab	Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab.
Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab	Eculizumab	Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab.
Group 1: 100 mg Danicopan TID + Eculizumab	Eculizumab	Starting dose of 100 mg danicopan TID in combination with eculizumab.
Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab	Eculizumab	Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab.

Primary Outcome Measures

Name	Time	Method
Change From Baseline In Hemoglobin At Week 24	Baseline, Week 24

Secondary Outcome Measures

Name	Time	Method
Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment	Within 24 weeks prior to first dose and during 24-week treatment period
Change From Baseline In Lactate Dehydrogenase At Week 24	Baseline, Week 24
Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment	Within 24 weeks prior to first dose and during 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	Day 1 (after dosing) through end of study (maximum exposure: 1631 days)	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.