Pivotal study of danicopan as add-on therapy to a C5 inhibitor (eculizumab or ravulizumab) in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who have Clinically Evident EVH

• Register: JPRN
• Last refreshed on: 17 October 2023
• Main ID: JPRN-jRCT2021210014
• Date of registration: 28/06/2021
• Prospective Registration: Yes
• Primary sponsor: Kamata Takeo
• Public title: Pivotal study of danicopan as add-on therapy to a C5 inhibitor (eculizumab or ravulizumab) in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who have Clinically Evident EVH
• Scientific title: A Phase 3 Study of Danicopan (ALXN2040) as Add-on Therapy to a C5 Inhibitor (Eculizumab or Ravulizumab) in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH)
• Date of first enrolment: 28/06/2021
• Target sample size: 84
• Recruitment status: Recruiting
• URL: https://jrct.niph.go.jp/latest-detail/jRCT2021210014
• Study type: Interventional
• Study design: randomized controlled trial, double blind, placebo control, parallel assignment, treatment purpose
• Phase: 3

Countries of recruitment

America, Japan

Contacts

• Name: Takeo Kamata
• Affiliation: Alexion Pharma GK

• Name: Takeo Kamata
• Affiliation: Alexion Pharma GK

Key inclusion & exclusion criteria

Inclusion criteria: 1 Diagnosis of PNH
2 Clinically Evident Extravascular hemolysis defined by:
Anemia, Hgb is 9.5 g per dL or less than 9.5, with absolute reticulocyte count 120000 per microL or more.
At least 1 packed RBC or whole blood transfusion within 6 months prior to the start of the study
3 Receiving a C5 inhibitor for at least 6 months prior to Day 1 in this study at an approved dose or higher and with no change in dose or interval for at least 24 weeks preceding Day 1. For those patients who recently switched from eculizumab to ravulizumab, they must have received at least the loading dose and 3 maintenance doses of ravulizumab preceding Day 1.
4 Platelet count 30,000 per microL or more than 30,000 per microL without the need for platelet transfusions
5 Absolute neutrophil counts 750 per microL or more
6 Documentation of vaccination for Neisseria meningitidis: All patients must be vaccinated against meningococcal infections within 3 years prior to, or at the time of initiating study
Age 18 years or older.
Exclusion criteria: 1 History of a major organ transplant or hematopoietic stem cell transplantation
2 Known aplastic anemia or other bone marrow failure that requires HSCT or other therapies including anti-thymocyte globulin and or immunosuppressants
4 Known or suspected complement deficiency
8 Laboratory abnormalities at screening, including:
Alanine aminotransferase more than 2 x ULN
Direct bilirubin more than 2 x ULN
11 Current evidence of biliary cholestasis
13 Estimated glomerular filtration rate less than 30 mL per min per 1.73 m2 and or are on dialysis.

Age minimum: >= 18age old
Age maximum: Not applicable
Gender: Both

Health Condition(s) or Problem(s) studied

Paroxysmal Nocturnal Hemoglobinuria
Paroxysmal Nocturnal Hemoglobinuria

D006457

Paroxysmal Nocturnal Hemoglobinuria

Intervention(s)

Double blinded

Additional Danicopan (ALXN2040) given to patients diagnosed with paroxysmal nocturnal hemoglobinuria and receiving complement C5 inhibitors

Primary Outcome(s)

Change in hemoglobin (Hgb) relative to baseline after 12 weeks of treatment

Secondary Outcome(s)

Proportion of patients with transfusion avoidance

Secondary ID(s)

NCT04469465

Ethics review

Status: Approval
Approval date:
Contact:

[e-mail]

Fukushima medical University Hospital

[phone]

[e-mail]