Myelodysplastic Syndrome Clinical Trial
Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)
Summary
The main objective of this study is to evaluate the efficacy of danicopan as add-on therapy to a complement component 5 (C5) inhibitor (eculizumab or ravulizumab) in participants with PNH who have clinically evident EVH.
Full Description
This is a multiple-region, randomized, double-blind, placebo controlled, multiple-dose, study in participants with PNH who have clinically evident EVH on a C5 inhibitor (eculizumab or ravulizumab).
Participants will be randomized to receive danicopan or placebo, in a 2:1 ratio for 12 weeks (Treatment Period 1) in addition to their C5 inhibitor (eculizumab or ravulizumab) therapy. At Week 12, participants randomized to receive placebo will be switched to danicopan in addition to their C5 inhibitor for an additional 12 weeks (Treatment Period 2) and participants randomized to danicopan will continue on danicopan for an additional 12 weeks, while remaining on their ongoing C5 inhibitor therapy.
At the end of the 2 treatment periods (Week 24), participants may enter a Long-Term Extension (LTE) Period and continue to receive danicopan in addition to their C5 inhibitor therapy. The Long-Term Extension period will consist of a first year of LTE(Year1) and a second year of optional LTE(Year2).All patients will complete 72 weeks of LTE(Year 1) assessments. After Week 72 (at the end of the first year of LTE), patients have the choice to complete participation in this study or continue to the optional second year (Year2) of LTE.
Eligibility Criteria
Inclusion Criteria:
Diagnosis of PNH
Clinically Evident EVH defined by:
Anemia (Hgb ≤9.5 gram/deciliter) with absolute reticulocyte count ≥120 x 10^9/liter
Receiving an approved C5 inhibitor for at least 6 months prior to Day 1
Platelet count ≥30,000/microliters (µL)
Absolute neutrophil counts ≥500/μL
Documentation of/or willingness to receive vaccinations for N. meningiditis and prophylactic antibiotics as required
Exclusion Criteria:
History of a major organ transplant or hematopoietic stem cell transplantation (HSCT)
Participants with known aplastic anemia or other bone marrow failure that requires HSCT or other therapies including anti-thymocyte globulin and/or immunosuppressants
Known or suspected complement deficiency
Laboratory abnormalities at screening, including:
Alanine aminotransferase >2 x ULN (>3 x ULN in case of patients with documented liver iron overload defined by serum ferratin values
500 ng/ML)
Direct bilirubin >2 x ULN (unless due to EVH or documented Gilbert's Syndrome)
Current evidence of biliary cholestasis
Estimated glomerular filtration rate of <30 milliliters/minute/1.73 meter squared and/or are on dialysis
Evidence of human immunodeficiency virus, hepatitis B, or active hepatitis C infection at screening
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There are 62 Locations for this study
Los Angeles California, 90089, United States
Weston Florida, 33331, United States
Chicago Illinois, 60612, United States
Kalamazoo Michigan, 49007, United States
New York New York, 10065, United States
Dallas Texas, 75390, United States
Milwaukee Wisconsin, 53212, United States
Belem , 66053, Brazil
Curitiba , 80810, Brazil
Goiania , 74605, Brazil
Porto Alegre , 90110, Brazil
Rio De De Janeiro , 20211, Brazil
Toronto Ontario, M5G 2, Canada
Brno , 625 0, Czechia
Lille , 59037, France
Paris , 75010, France
Pessac , 33604, France
Pierre Benite Cedex , 69495, France
Ulm , 89081, Germany
Athens , 11527, Greece
Thessaloniki , 57010, Greece
Haifa , 31048, Israel
Jerusalem , 91120, Israel
Avellino , 83100, Italy
Bassano del Grappa , 36061, Italy
Firenze , 50134, Italy
Milano , 20122, Italy
Reggio Calabria , 89131, Italy
Roma , 00161, Italy
Bunkyo-Ku , 113 8, Japan
Fukuoka , 812-8, Japan
Kashiwa-shi , 277-8, Japan
Kyoto-shi , 605-0, Japan
Nagakute-shi , 480-1, Japan
Ogaki-shi , 503-8, Japan
Osaka-shi , 530-8, Japan
Osakasayama , 589-8, Japan
Shibuya-ku , 150-8, Japan
Tanabe-shi , 646-8, Japan
Toyoake-shi , 470-1, Japan
Tsukuba-shi , 305-8, Japan
Daejeon , 35015, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 06351, Korea, Republic of
Seoul , 06591, Korea, Republic of
Suwon , 16247, Korea, Republic of
Kota Kinabalu , 88586, Malaysia
Kuching , 93586, Malaysia
Miri , 98000, Malaysia
Maastricht , 6229 , Netherlands
Gdansk , 80-21, Poland
Barcelona , 08036, Spain
Barcelona , 08916, Spain
Las Palmas de Gran Canaria , 35020, Spain
Madrid , 28040, Spain
Majadahonda , 28222, Spain
Sevilla , 41013, Spain
Taipei , 100, Taiwan
Bangkok , 10330, Thailand
Airdrie , ML6 0, United Kingdom
Leeds , BD7 1, United Kingdom
London , SE5 9, United Kingdom
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