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

NCT06449001 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: D7332C00006ALXN2040-PNH-302
• Study Type: interventional
• Target: 6
• Locations: 3 countries
• Sites: 4

Brief Summary

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).

Conditions

Paroxysmal Nocturnal Hemoglobinuria; PNH; Extravascular Hemolysis

Keywords

Paroxysmal Nocturnal Hemoglobinuria; PNH; Extravascular Hemolysis; Ravulizumab; Eculizumab; Danicopan

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hemoglobin (Hgb) Concentration at Week 12

  Baseline, Week 12

Secondary Outcomes (9)

• 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

Study Arms (1)

Danicopan

EXPERIMENTAL

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

Interventions

Danicopan DRUG

Participants will receive danicopan on a weight-based dosing regimen.

Danicopan

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Alexion Pharmaceuticals, Inc.: lead

Study Sites (4)

Research Site

Saskatoon, Saskatchewan, S7N 0W8, Canada

RECRUITING

Research Site

Paris, 77019, France

RECRUITING

Research Site

Leeds, LS9 7TF, United Kingdom

RECRUITING

Research Site

London, SE5 9RS, United Kingdom

RECRUITING

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

Central Study Contacts

Alexion Pharmaceuticals, Inc. (Sponsor)

CONTACT

1-855-752-2356; clinicaltrials@alexion.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 7, 2024
• Study Start: August 11, 2025
• Primary Completion (Estimated): May 28, 2027
• Study Completion (Estimated): March 10, 2028
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

CA (1); GB (2); FR (1)