Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)

NCT04469465 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ALXN2040-PNH-3012019-003829-18
• Study Type: interventional
• Target: 86
• Locations: 18 countries
• Sites: 62

Brief 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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

Paroxysmal Nocturnal Hemoglobinuria (PNH); Extravascular Hemolysis (EVH); Factor D inhibitor; Complement; Danicopan; C5 inhibitor

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hgb at Week 12

  Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.

  Baseline, Week 12

Secondary Outcomes (18)

• Percentage of Participants With Hgb Increase of ≥2 Grams/Deciliter (g/dL) (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12

  Week 12

• Percentage of Participants With Transfusion Avoidance Through Week 12

  Week 12

• Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 12

  Baseline, Week 12

• Change From Baseline in Absolute Reticulocyte Count at Week 12

  Baseline, Week 12

• Change in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment

  24 weeks prior to initiation of treatment to 24 weeks post initiation of treatment

Study Arms (2)

Danicopan + C5 Inhibitor

EXPERIMENTAL

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).

Drug: Danicopan; Drug: C5 Inhibitor

Placebo + C5 Inhibitor

PLACEBO COMPARATOR

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).

Drug: Placebo; Drug: C5 Inhibitor

Interventions

Danicopan DRUG

Oral tablet

Also known as: ALXN2040

Danicopan + C5 Inhibitor

Placebo DRUG

Oral tablet

Placebo + C5 Inhibitor

C5 Inhibitor DRUG

Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule.

Danicopan + C5 Inhibitor; Placebo + C5 Inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (62)

Research Site

Los Angeles, California, 90089, United States

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Weston, Florida, 33331, United States

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Chicago, Illinois, 60612, United States

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Kalamazoo, Michigan, 49007, United States

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New York, New York, 10065, United States

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Dallas, Texas, 75390, United States

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Milwaukee, Wisconsin, 53212, United States

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Belém, 66053-000, Brazil

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Curitiba, 80810-050, Brazil

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Goiânia, 74605-020, Brazil

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Porto Alegre, 90110-270, Brazil

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Rio de de Janeiro, 20211030, Brazil

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Toronto, Ontario, M5G 2C4, Canada

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Brno, 625 00, Czechia

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Lille, 59037, France

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Paris, 75010, France

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Pessac, 33604, France

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Pierre-Bénite, 69495, France

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Ulm, 89081, Germany

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Athens, 11527, Greece

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Thessaloniki, 57010, Greece

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Haifa, 31048, Israel

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Jerusalem, 91120, Israel

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Avellino, 83100, Italy

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Bassano del Grappa, 36061, Italy

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Florence, 50134, Italy

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Milan, 20122, Italy

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Reggio Calabria, 89131, Italy

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Roma, 00161, Italy

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Bunkyō City, 113 8603, Japan

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Fukuoka, 812-8582, Japan

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Kashiwa-shi, 277-8567, Japan

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Kyoto, 605-0981, Japan

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Nagakute-shi, 480-1195, Japan

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Ogaki-shi, 503-8502, Japan

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Osaka, 530-8480, Japan

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Sayama, 589-8511, Japan

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Shibuya-ku, 150-8935, Japan

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Tanabe-shi, 646-8588, Japan

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Toyoake-shi, 470-1192, Japan

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Tsukuba, 305-8576, Japan

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Kota Kinabalu, 88586, Malaysia

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Kuching, 93586, Malaysia

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Miri, 98000, Malaysia

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Maastricht, 6229 HX, Netherlands

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Gdansk, 80-214, Poland

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Daejeon, 35015, South Korea

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Seoul, 03722, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Suwon, 16247, South Korea

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Barcelona, 08036, Spain

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Barcelona, 08916, Spain

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Las Palmas de Gran Canaria, 35020, Spain

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Madrid, 28040, Spain

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Majadahonda, 28222, Spain

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Seville, 41013, Spain

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Taipei, 100, Taiwan

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Bangkok, 10330, Thailand

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Airdrie, ML6 0JS, United Kingdom

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Leeds, BD7 1DP, United Kingdom

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London, SE5 9NU, United Kingdom

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Related Publications (2)

• 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.

  PMID: 38030318 RESULT

• 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.

  PMID: 39700502 DERIVED

Related Links

• 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
• Related Info

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Hemolysis

Interventions

danicopan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

+1 855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2020
• First Posted: July 14, 2020
• Study Start: December 16, 2020
• Primary Completion: June 29, 2022
• Study Completion: January 16, 2024
• Last Updated: May 4, 2025
• Results First Posted: July 24, 2023

Record last verified: 2025-04

Locations

CA (1); ES (6); TH (1); PL (1); DE (1); IL (2); GR (2); US (7); BR (5); MY (3); TW (1); NL (1); JP (12); IT (6); KR (5); CZ (1); FR (4); GB (3)