Clinical trial NCT03472885: Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab
Official title: A Phase 2 Open-label Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: PNH
Paroxysmal Nocturnal Hemoglobinuria
ACH-0144471
Danicopan
Eculizumab
ALXN2040
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Achillion, a wholly owned subsidiary of Alexion
First posted: 2018-03-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Four groups will be studied and enrolled sequentially.
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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.

Primary outcomes:
measure: Change From Baseline In Hemoglobin At Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment
timeFrame: Within 24 weeks prior to first dose and during 24-week treatment period
measure: Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment
timeFrame: Within 24 weeks prior to first dose and during 24-week treatment period
measure: Change From Baseline In Lactate Dehydrogenase At Week 24
timeFrame: Baseline, Week 24
measure: Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug
timeFrame: Day 1 (after dosing) through end of study (maximum exposure: 1631 days)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Clinical Study Site
state: Maryland
city: Cleveland
country: United States
facility: Clinical Study Site
state: Ohio
city: Florence
country: Italy
facility: Clinical Study Site
city: Naples
country: Italy
facility: Clinical Study Site
city: London
country: United Kingdom
facility: Clinical Study Site
Study officials:
References:
citation: Kulasekararaj AG, Risitano AM, Maciejewski JP, Notaro R, Browett P, Lee JW, Huang M, Geffner M, Brodsky RA. Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab. Blood. 2021 Nov 18;138(20):1928-1938. doi: 10.1182/blood.2021011388.