A Post-Authorization Safety Study (PASS) to Characterize Safety Events and Special Conditions, Such as Pregnancy and Infant Outcomes, in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients Treated With Crovalimab Within the IPIG Registry

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Evaluation of patient-reported outcomes

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Observational post-authorization safety study (PASS)

Study drug and medical condition

• Medicinal product name:
  PIASKY
• Study drug International non-proprietary name (INN) or common name:
  CROVALIMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AJ07) crovalimab

  crovalimab
• Medical condition to be studied:
  Paroxysmal nocturnal haemoglobinuria

Population studied

• Short description of the study population:
  Participants with PNH who are treated with crovalimab and have available data from the Crovalimab Silo, including participants who are pregnant and information from their infants.
• Age groups:
  • In utero
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • 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)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  300

Study design details

• Study design:
  Data for this study will be collected as part of the Crovalimab Silo registry. This encompasses retrospective & prospective data (participants’ characteristics, clinical outcomes & crovalimab exposure) for all participants treated with crovalimab, including pregnant participants & their infants.
• Main study objective:
  The aim of this study is to characterize the safety profile of crovalimab in participants with PNH, with a specific focus on adverse events of special interest (AESIs). ; This study also aims to assess adverse events (AEs), serious adverse events (SAEs), pregnancy, and infant outcomes in female participants with PNH exposed to crovalimab during pregnancy and through breastfeeding.
• Setting:
  Inclusion criteria:; -Participants with PNH confirmed by flow cytometry.; -Participants and/or parent/legally authorized representative provide written informed consent/assent to participate in the Core Registry and the Crovalimab Silo prior to any registry-related data collection, in a manner approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) and local regulations.; -Participants with PNH currently being treated with or who start crovalimab during the study period.; ; Exclusion criteria:; -Participants with PNH participating in an interventional PNH clinical trial while receiving crovalimab (i.e., in combination with other therapy), with exception of participants with PNH participating in the extension period of COMMODORE/COMPOSER Roche studies and Post Trial Access Programs.; ; The exclusion criteria for all participants will also be applicable to assess crovalimab exposure during pregnancy, as well as pregnancy, infant, and breastfeeding outcomes.;
• Comparators:
  None
• Outcomes:
  Primary Outcomes:; -Presence, type, onset and resolution date and hospitalizations of serious infections; -Presence, type, onset and resolution date and hospitalizations of Meningococcal and other infections with encapsulated bacteria; -Development or Worsening of any Neurological Condition; -Presence and type of malignancy, onset and resolution date; -Serious hemolysis events, onset and resolution date; -Serious Hemolysis after crovalimab discontinuation; -Number of transient immune complex reactions; -Number of infusion and injection-related reactions; -Pregnancy-related outcomes [Ectopic pregnancy, spontaneous abortion, pregnancy terminations, fetal death or stillbirth, live birth, preterm birth, preeclampsia, eclampsia, Preterm Prelabor Rupture of Membrane (PPROM)]; -Infant-related outcomes [Size for gestational age, low birth weight, postnatal growth deficiency or failure to thrive (FTT), infant developmental deficiency, congenital malformations, serious and severe infections, and hospitalization of infants; -Number of neonatal deaths, perinatal deaths, infant deaths and maternal deaths; -Any adverse events (AEs) during pregnancy; -Any AEs for lactating females and infants through breastfeeding; -Any AEs experienced by the infant at birth and up to through at least the first year of life; ; Secondary Outcomes:; -AEs and serious adverse events (SAEs) (not included as AESIs); -Clinical outcome and laboratory test results related to PNH among participants who experienced an AESI; -Fatigue assessment using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaire for participants who experienced an AESI
• Data analysis plan:
  Descriptive statistics will be reported using summary tables and figures (where appropriate). Continuous variables will be summarized using mean, standard deviation, median, range (min-max) and interquartile range. Categorical variables will be summarized using counts and proportions (%).; ; Incidence and incidence rate (IRs; in person-years) and their 95% confidence interval (Cis) of AESIs, SAEs and AEs will be calculated. The exact 95% CIs will be computed using the Clopper-Pearson method.; ; Incidence proportions will be calculated as the proportion of participants afflicted with each of the AESIs, SAEs, and AEs up to the data extraction date.