A Long-term Safety and Efficacy Study of Danicopan as an Add-on Therapy to Complement Component 5 Inhibitor (C5i) in Participants With PNH

A Long-term Extension (LTE) Study to Characterize the Safety and Efficacy of Danicopan as an Add-on Therapy to a Complement Component 5 Inhibitor (C5i) in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Previously Treated With Danicopan in an Alexion-sponsored Clinical Study

This is a single-arm long-term extension study that will enroll participants with PNH who have completed participation in Alexion-sponsored clinical studies with danicopan as an add on therapy to a C5i.

Study Overview

• Status: Active, not recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: Danicopan

Detailed Description

The total duration of the study will be up to 3 years. Eligible participants must complete all study assessments on the parent protocol before starting this study. All participants entering this study will receive danicopan as an add-on to a background C5i therapy. The only allowed C5i therapies are eculizumab and ravulizumab.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil, 90110-270
    • Research Site
  • Rio de Janeiro, Brazil, 20211-080
    • Research Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
• France
  • Lille, France, 59037
    • Research Site
  • Paris, France, 75010
    • Research Site
  • Pessac, France, 33604
    • Research Site
  • Pierre-Bénite, France, 69495
    • Research Site
• Greece
  • Athens, Greece, 11527
    • Research Site
  • Thessaloniki, Greece, 57010
    • Research Site
• Israel
  • Haifa, Israel, 31048
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
• Italy
  • Avellino, Italy, 83100
    • Research Site
  • Bassano del Grappa, Italy, 36061
    • Research Site
  • Florence, Italy, 50134
    • Research Site
  • Milan, Italy, 20122
    • Research Site
  • Reggio Calabria, Italy, 89131
    • Research Site
  • Roma, Italy, 161
    • Research Site
• Japan
  • Bunkyō City, Japan, 113 8603
    • Research Site
  • Kyoto, Japan, 605-0981
    • Research Site
  • Osaka, Japan, 530-8480
    • Research Site
  • Shibuya-ku, Japan, 150-8935
    • Research Site
  • Tsukuba, Japan, 305-8576
    • Research Site
• Malaysia
  • Kota Kinabalu, Malaysia, 88586
    • Research Site
  • Kuching, Malaysia, 93200
    • Research Site
  • Miri, Malaysia, 98000
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
• South Korea
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 06591
    • Research Site
  • Suwon, South Korea, 16247
    • Research Site
• Spain
  • Badalona, Spain, 8916
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Seville, Spain, 41013
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
• United Kingdom
  • Airdrie, United Kingdom, ML6 0JS
    • Research Site
  • Leeds, United Kingdom, LS9 7TF
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90089
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Research Site
  • New York
    • Long Island City, New York, United States, 11101
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390-9047
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• All participants who completed their participation in an Alexion sponsored clinical study with danicopan as an add on to a C5i treatment.
• Patient is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
• Documentation of vaccination for Neisseria meningitidis: All participants must be revaccinated as per national vaccination guidelines or local practice for vaccination use with complement inhibitors.

Key Exclusion Criteria:

• Any medical condition (for example, cardiac, pulmonary, renal, oncologic, or psychiatric) that, in the opinion of the Investigator, might interfere with participation in the study, pose any added risk to the participant, or confound the assessment of the participant.
• Patient has been permanently discontinued from danicopan in the parent study for any reason other than enrollment into this LTE study.
• Female participants who are pregnant, breastfeeding, or intending to conceive during the course of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Danicopan; Participants will receive their last dose of danicopan from the parent study the night prior to Day 1 of this LTE study and will continue daily treatment with danicopan together with their background C5i therapy.	Drug: Danicopan; Oral tablet; Other Names: ALXN2040, ACH-0144471

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Participants Experiencing Treatment-emergent Adverse Events (TEAEs) And Serious TEAEs	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change In Hemoglobin Values		Up to 3 years
Change In Absolute Reticulocyte Count		Up to 3 years
Change In Lactate Dehydrogenase (LDH)		Up to 3 years
Proportion Of Participants With LDH ≤ 1.5 × Upper Limit Of Normal		Up to 3 years
Proportion Of Participants With Transfusion Avoidance		Up to 3 years
Change In Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores	Total scores range from 0 to 52, with higher scores indicating better QoL.	Up to 3 years
Change In The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 Scale (QLQ-C30) Scores	Thirty questions related to QoL, with the first 28 questions scored on a 4-point scale (1 = not at all to 4 = very much) and the final 2 questions that probe the participant's overall health and QoL scored on a scale of 1 (very poor) to 7 (excellent).	Up to 3 years
Participants Experiencing TEAEs Leading To Discontinuation		Up to 3 years
Proportion of patients with Hgb increase ≥ 2g/dL in the absence of transfusion over time		Up to 3 years

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: May 20, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (Actual): May 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Complement; Danicopan; ALXN2040; Paroxysmal Nocturnal Hemoglobinuria (PNH); Extravascular Hemolysis (EVH); Factor D inhibitor; C5 inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hemoglobinuria, Paroxysmal; Hemolysis; danicopan
• Other Study ID Numbers: ALXN2040-PNH-303; 2021-004253-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No