An Observational Cohort Study to Assess Long-Term Safety of Danicopan Add-on Therapy in Patients with Paroxysmal Nocturnal Hemoglobinuria: Analysis of IPIG-Registry Data

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  VOYDEYA
• Study drug International non-proprietary name (INN) or common name:
  DANICOPAN
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AJ09) danicopan

  danicopan
• Medical condition to be studied:
  Paroxysmal nocturnal haemoglobinuria

Population studied

• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Nursing women

  Pregnant women
• Estimated number of subjects:
  50

Study design details

• Study design:
  This PASS uses primary and secondary data from the IPIG PNH Registry, collected retrospectively and prospectively. Primary data will assess Voydeya’s safety; retrospective data, including Alexion International PNH Registry, will describe medical history, participant characteristics, and clinical pro
• Main study objective:
  This study aims to characterize the long-term safety of danicopan as add-on therapy to ravulizumab or eculizumab for the treatment of adult patients with PNH who have residual hemolytic anemia.
• Setting:
  Persons: Adult participants with PNH with a detected proportion of PNH cells, who have provided written informed consent, are not participating in an interventional clinical study specific to PNH are eligible for participation in the IPIG PNH Registry. Those meeting the study inclusion/exclusion criteria will be selected.; ; Place: Participants enrolled in the global IPIG PNH Registry; ; Inclusion Criteria: (1) Adult participants aged ≥ 18 years at treatment initiation.; (2) Initiated treatment with Ultomiris, Soliris, and/or danicopan on or after IPIG or Alexion International PNH Registry enrollment; ; Exclusion Criteria: Participants without known year of birth, sex, informed consent date, or treatment status of danicopan and Ultomiris and/or Soliris.; ; Treatment Groups: (1) Participants ever-treated with danicopan as add-on therapy to ravulizumab/eculizumab on or after IPIG PNH Registry enrollment. (2) Participants initiating treatment with Ultomiris or Soliris on or after IPIG or Alexion ; International PNH Registry enrollment and without any danicopan treatment ; experience during follow-up.; ; Subpopulation of interest: Include participants ever-treated with danicopan as add-on therapy to ravulizumab/eculizumab and distinguish: (1) Participants with severe hepatic impairment; (2) Pregnant participants, pregnant partners of participants, or participants who are breastfeeding.;
• Comparators:
  The study population will consist of 2 treatment cohorts: (1) Participants ever-treated with danicopan as add-on therapy to ravulizumab/eculizumab on or after IPIG PNH Registry enrollment. (2) Participants initiating treatment with Ultomiris or Soliris on or after IPIG or Alexion International PNH Registry enrollment and without any danicopan treatment experience during follow-up.
• Outcomes:
  Primary Outcomes:; AEs (serious and nonserious) including for a subpopulation of patients with severe hepatic impairment ; Special situations and causes of death; Rate of meningococcal infection; Rate of serious infections; Rate of malignancies and hematologic abnormalities; ; Secondary Outcomes: ; Pregnancy-related outcomes and infant health abnormalities up to 12 months of age in pregnant participants, pregnant partners of participants, or participants who are breastfeeding only.; Demographic characteristics, medical history, PNH-specific treatment history, concomitant medications, and laboratory values.; Number of participants who discontinue danicopan and reasons for discontinuation.; ;
• Data analysis plan:
  Descriptive analyses: Continuous variables will be characterized with number of nonmissing observations, mean and standard deviation, median and interquartile range, minimum and maximum, and number of missing data. Categorical variables will be characterized by the frequency and percent distribution in each category for nonmissing data and missing data, as appropriate. The analysis will include 95% confidence intervals of means and percentages, as appropriate.; ; Outcome measure analysis: ; Event rates will be measured for participants in 1) the danicopan as add-on therapy to ravulizumab/eculizumab cohort, 2) IPIG Registry Ultomiris/Soliris monotherapy cohorts (treated exposure period only), ; and 3) Ultomiris/Soliris monotherapy cohorts (treated exposure period only). The event rate for the Ultomiris/Soliris monotherapy cohort inclusive of events recorded in the Alexion PNH registry will be presented in the final PASS report.; ; Incidence of meningococcal infections, serious infections, and malignancies and hematological abnormalities will also be assessed in danicopan-treated participants by exposure period pending feasibility. Specific to the characterization of clinical events with bone marrow pathology or other hematological disorders, an ever-exposed analysis will also be performed in the danicopan as add-on therapy to ravulizumab/eculizumab cohort and the IPIG Registry Ultomiris/Soliris ; monotherapy cohort.;