Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)
NCT ID: NCT04469465
Last Updated: 2025-05-04
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
86 participants
INTERVENTIONAL
2020-12-16
2024-01-16
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Danicopan + C5 Inhibitor
Participants will receive danicopan, in addition to their C5 inhibitor therapy, for 24 weeks (12 weeks in Treatment Period 1, followed by 12 weeks in Treatment Period 2).
Danicopan
Oral tablet
C5 Inhibitor
Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule.
Placebo + C5 Inhibitor
Participants will receive placebo, in addition to their C5 inhibitor therapy, for 12 weeks during Treatment Period 1. At Week 12, participants randomized to receive placebo will be switched to danicopan for an additional 12 weeks (Treatment Period 2).
Placebo
Oral tablet
C5 Inhibitor
Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule.
Interventions
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Danicopan
Oral tablet
Placebo
Oral tablet
C5 Inhibitor
Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Alexion Pharmaceuticals, Inc.
INDUSTRY
Responsible Party
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Locations
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Research Site
Los Angeles, California, United States
Research Site
Weston, Florida, United States
Research Site
Chicago, Illinois, United States
Research Site
Kalamazoo, Michigan, United States
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New York, New York, United States
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Dallas, Texas, United States
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Milwaukee, Wisconsin, United States
Research Site
Belém, , Brazil
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Curitiba, , Brazil
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Goiânia, , Brazil
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Porto Alegre, , Brazil
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Rio de de Janeiro, , Brazil
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Toronto, Ontario, Canada
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Brno, , Czechia
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Lille, , France
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Paris, , France
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Pessac, , France
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Pierre-Bénite, , France
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Ulm, , Germany
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Athens, , Greece
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Thessaloniki, , Greece
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Haifa, , Israel
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Jerusalem, , Israel
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Avellino, , Italy
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Bassano del Grappa, , Italy
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Florence, , Italy
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Milan, , Italy
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Reggio Calabria, , Italy
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Roma, , Italy
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Bunkyō City, , Japan
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Fukuoka, , Japan
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Kashiwa-shi, , Japan
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Kyoto, , Japan
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Nagakute-shi, , Japan
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Ogaki-shi, , Japan
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Osaka, , Japan
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Sayama, , Japan
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Shibuya-ku, , Japan
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Tanabe-shi, , Japan
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Toyoake-shi, , Japan
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Tsukuba, , Japan
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Kota Kinabalu, , Malaysia
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Kuching, , Malaysia
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Miri, , Malaysia
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Maastricht, , Netherlands
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Gdansk, , Poland
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Daejeon, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Suwon, , South Korea
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Barcelona, , Spain
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Barcelona, , Spain
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Las Palmas de Gran Canaria, , Spain
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Madrid, , Spain
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Majadahonda, , Spain
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Seville, , Spain
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Taipei, , Taiwan
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Bangkok, , Thailand
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Airdrie, , United Kingdom
Research Site
Leeds, , United Kingdom
Research Site
London, , United Kingdom
Countries
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References
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Lee JW, Griffin M, Kim JS, Lee Lee LW, Piatek C, Nishimura JI, Carrillo Infante C, Jain D, Liu P, Filippov G, Sicre de Fontbrune F, Risitano A, Kulasekararaj AG; ALXN2040-PNH-301 Investigators. Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial. Lancet Haematol. 2023 Dec;10(12):e955-e965. doi: 10.1016/S2352-3026(23)00315-0.
Kulasekararaj A, Griffin M, Piatek C, Shammo J, Nishimura JI, Patriquin C, Schrezenmeier H, Barcellini W, Panse J, Gaya A, Patel Y, Liu P, Filippov G, Sicre de Fontbrune F, Risitano A, Lee JW. Long-term efficacy and safety of danicopan as add-on therapy to ravulizumab or eculizumab in PNH with significant EVH. Blood. 2025 Feb 20;145(8):811-822. doi: 10.1182/blood.2024026299.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Danicopan (ACH-4471) in Untreated Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Phase 2, Open-label, Proof of Concept Study of the Oral, Small Molecule Factor D Inhibitor
Other Identifiers
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2019-003829-18
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
ALXN2040-PNH-301
Identifier Type: -
Identifier Source: org_study_id
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