Characterization of Participants treated with Ultomiris and Long term safety outcomes: an IPIG registry based study

Study type

• Study topic:
  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

• Name of medicine:
  ULTOMIRIS
• Study drug International non-proprietary name (INN) or common name:
  RAVULIZUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AJ02) ravulizumab

  ravulizumab

Population studied

• Short description of the study population:
  Adult and pediatric participants with PNH
• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  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)
• Estimated number of subjects:
  300

Study design details

• Study design:
  This non-interventional cohort study utilizes data from the multinational, multicenter, observational IPIG PNH registry
• Main study objective:
  Primary objectives include characterizing the safety of Ultomiris in participants with PNH. ; Additionally, the study aims to characterize the incidence of targeted clinical putcomes (MAVE, TE, malignancy, serious infection, impaired renal function, impaired hepatic function, hemolysis, mortality, bone marrow transplant) among participants with PNH.
• Setting:
  Persons: Participants (adult and pediatric) with PNH diagnosis confirmed by flow cytometry and who meet the inclusion/exclusion criteria will be invited to participate in the IPIG PNH Registry. ; All participants with PNH will be eligible, regardless of whether they are receiving PNH-specific therapy and regardless of what type of therapy they are receiving.; ; Place: Participants enrolled in the global IPIG PNH Registry; ; Inclusion Criteria:; Participants of any age and sex, with PNH with a detected proportion of PNH cells (PNH clone) of at least 1% at registry enrollment, initiating Ultomiris on or after enrollment into the Alexion or IPIG PNH Registries.; ; Ability to comprehend and sign consent or able to give assent to have data entered in the IPIG PNH Registry. Participants who are minors must have parent/legal guardian consent. Participants who are minors must be willing and able to give assent, if applicable as determined by the Ethics Committees/Institutional Review Boards (IECs/IRBs). Upon attaining adulthood, these participants must be re-consented.; ; Exclusion Criteria:; Participants currently enrolled in an interventional clinical study for treatment of PNH cannot be enrolled in the IPIG PNH Registry while enrolled/participating in the clinical study for PNH therapy.; ; Participants without known year of birth, sex, Ultomiris treatment status, or informed consent date.; ; Treatment groups: Participants will be categorized into treatment groups by prior Soliris treatment status: Prior Soliris treatment, without prior Soliris treatment, Unknown prior Soliris treatment.
• Comparators:
  N/A
• Outcomes:
  Participant demographics, medical history, clinical events, laboratory values, concomitant medication, prior treatment with Soliris, and Ultomiris dose will be summarized at initiation of Ultomiris using descriptive analyses. Treatment and registry discontinuation along with associated reasons, pregnancy and fetal outcomes, and SAEs collected during registry follow-up will also be summarized.; ; Clinical events, including death, MAVEs (including thrombosis), infection, malignancy, impaired renal function, impaired hepatic function, Ultomiris infusion reactions, hemolysis, pulmonary hypertension, and bone marrow transplant, will be summarized by event rates.
• Data analysis plan:
  All analyses will be carried out using SAS® version 9.4 or higher. Statistical analysis will be descriptive only. No formal hypothesis testing will be performed.; ; Continuous variables will be characterized with number of non-missing 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 percentage distribution in each category for non-missing data, as appropriate. The analysis will include 95% confidence intervals of means and percentages, as appropriate.; ; Event rates are calculated by: The total number of events and the total person-years during the follow-up period of interest will be determined. The event rate will be the number of events divided by the person-years. ; Person-years are calculated under the definition of exposure for all participants included in the study population, regardless of whether they had an event. ; The event rate will be calculated using a Poisson regression with over-dispersion or generalized estimating equations using a log link, as is appropriate.