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

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06449001
• Other study ID #: D7332C00006
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: August 23, 2024
• Est. completion date: January 28, 2028

Study information

• Verified date: May 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: Alexion Pharmaceuticals, Inc. (Sponsor)
• Phone: 1-855-752-2356
• Email: clinicaltrials[@]alexion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: January 28, 2028
• Est. primary completion date: January 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

• 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

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.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Hemolysis
• Paroxysmal Nocturnal Hemoglobinuria
• PNH

Intervention

Drug:
• Danicopan
Participants will receive danicopan on a weight-based dosing regimen.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Outcome

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