Study of Danicopan as Add-on Treatment to Ravulizumab or Eculizumab in Pediatric Participants With PNH Who Have Clinically Significant Extravascular Hemolysis

A Phase 3 Open-Label Study of Danicopan as Add-on Treatment to Ravulizumab or Eculizumab in Pediatric Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Significant Extravascular Hemolysis

The primary objective of this study is to evaluate efficacy of danicopan as add-on treatment to ravulizumab or eculizumab as assessed by hemoglobin (Hgb) change from Baseline at Week 12 in pediatric participants with paroxysmal nocturnal hemoglobinuria (PNH) and clinically significant extravascular hemolysis (CS-EVH).

Study Overview

• Status: Recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria; PNH; Extravascular Hemolysis
• Intervention / Treatment: Drug: Danicopan

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alexion Pharmaceuticals, Inc. (Sponsor); Phone Number: 1-855-752-2356; Email: clinicaltrials@alexion.com

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Recruiting
      • Research Site
• France
  • Paris, France, 77019
    • Recruiting
    • Research Site
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of PNH.
• CS-EVH defined by: Anemia: Hgb ≤ 11.0 g/dL, and absolute reticulocyte count ≥ 100 × 109/L
• Treated with ravulizumab or eculizumab for at least 12 weeks immediately preceding Day 1, the dose received should be stable during this period, and there should be no anticipated changes in dosage or interval during the first 12 weeks of this study.
• all participants must be vaccinated against meningococcal infection from serogroups A, C, W, and Y and serogroup B within 3 years prior to, or at least 14 days prior to Day 1
• vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae

Exclusion Criteria:

• Platelet count < 30000/μL or there is a need for platelet transfusions.
• ANC < 500/μL.

• Clinically significant laboratory abnormalities related to liver function, including:

  • ALT > 2 × ULN or ALT > 3 × ULN for participants with documented liver iron overload defined by serum ferritin values ≥ 500 ng/mL.
  • Direct bilirubin > 2 × ULN, unless, in the Investigator's opinion, is due to hemolysis or Gilbert's syndrome based on medical history.
• Current evidence of biliary cholestasis.
• Known aplastic anemia or other bone marrow failure that requires HSCT or other therapies, including anti-thymocyte globulin and immunosuppressants unless the dosage of immunosuppressant has been stable for at least 12 weeks before Day 1 and is expected to remain stable through Week 12.
• History of a major organ transplant (eg, heart, lung, kidney, liver) or HSCT.
• Known or suspected complement deficiency.
• Active bacterial or viral infection, a body temperature > 38°C on 2 consecutive daily measures, evidence of other infection, or history of any febrile illness within 14 days prior to first study intervention administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• 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 a 12-week weight-based open-label treatment period and up to 1 year open-label long term extension period.	Drug: Danicopan; Participants will receive danicopan on a weight-based dosing regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Hemoglobin (Hgb) Concentration at Week 12	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) of Danicopan	Day 1 up to Week 12
Number of Participants With Transfusion Avoidance Through Weeks 12 and 24	Weeks 12 and 24
Change From Baseline in Absolute Reticulocyte Count at Weeks 12 and 24	Baseline, Weeks 12 and 24
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales Score at Weeks 12 and 24	Baseline, Weeks 12 and 24
Change from Baseline in Pediatric Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 12 and 24	Baseline, Weeks 12 and 24
Acceptability and Palatability Questionnaire Score	Week 2
Change from Baseline in Hgb Concentration at Week 24	Baseline, Week 24
Change from Baseline in Serum Alternative Pathway (AP) Activity	Baseline up to Week 64
Change from Baseline in Plasma Bb Concentrations	Baseline up to Week 64

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2025
• Primary Completion (Estimated): May 28, 2027
• Study Completion (Estimated): March 10, 2028

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 7, 2024

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Danicopan; PNH; Paroxysmal Nocturnal Hemoglobinuria; Eculizumab; Ravulizumab; Extravascular Hemolysis
• 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: D7332C00006; ALXN2040-PNH-302 (Other Identifier: Alexion)

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; SAP; 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