Study of Danicopan as Add-on Treatment to Ravulizumab or Eculizumab in Pediatric Participants With PNH Who Have Clinically Significant Extravascular Hemolysis
- Conditions
- Paroxysmal Nocturnal HemoglobinuriaPNHExtravascular Hemolysis
- Interventions
- Registration Number
- NCT06449001
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 6
- Confirmed diagnosis of PNH.
- CS-EVH defined by: Anemia: Hgb ≤ 10.5 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
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Platelet count < 30000/μL or there is a need for platelet transfusions.
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ANC < 500/μL.
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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.
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Current evidence of biliary cholestasis.
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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.
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History of a major organ transplant (eg, heart, lung, kidney, liver) or HSCT.
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Known or suspected complement deficiency.
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Danicopan Danicopan Participants will receive a 12-week weight-based open-label treatment period at Day 1 for up to 1 year open-label long term extension period.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin (Hgb) Concentration at Week 12 Baseline, Week 12
- Secondary Outcome Measures
Name Time Method Number of Participants With Transfusion Avoidance Through Weeks 12 and 24 Weeks 12 and 24 Maximum Plasma Concentration (Cmax) of Danicopan Day 1 up to Week 12 Change From Baseline in Absolute Reticulocyte Count 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 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 Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales 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
Trial Locations
- Locations (1)
Research Site
🇫🇷Paris, France