REAL-CARE: Real-world Effectiveness of Iptacopan in Italian Patients With Paroxysmal Nocturnal Hemoglobinuria (REAL-CARE)

REAL-CARE: Real-world Effectiveness of iptacopAn in itaLian Patients With Paroxysmal noCturnAl HemoglobinuRia: an Observational Study

This study evaluates iptacopan effectiveness and safety in routine clinical practice, with a focus on hematological response, transfusion avoidance, and patient-reported outcomes.

The primary objective of the REAL-CARE study is to is to assess the long-term hematological response following iptacopan initiation. This will be assessed through the absolute change in hemoglobin (Hb) levels at 12 months post-initiation, and the proportion of patients who remain free from red blood cell (RBC) transfusions, prescribed as per local requirement and based on Investigator's judgment, from Day 14 through Month 12 after starting iptacopan.

Study Overview

• Status: Recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Detailed Description

This is a local, multicenter, observational study with retrospective, retro-prospective and prospective cohorts. Adult patients with PNH either naïve to iptacopan or transitioning from the Managed Access Program (MAP) starting from January 2023 will be enrolled. Primary data will be collected prospectively; secondary data will be retrieved retrospectively from patients previously treated under MAP. A mix of primary and secondary data will be collected in retro-prospective patients. Patients will be indexed on the date of iptacopan initiation and will be followed up for 24 months or until iptacopan discontinuation (due to occurrence of an adverse event, lack of efficacy etc), clinical decision, death, administrative issues, consent withdrawal or loss to follow-up, whichever comes first. The enrollment period is planned to last 15 months, with potential adjustments based on enrollment progress. No treatment decision will be influenced by study participation.

No extra visits, examinations, or procedures are imposed. Questionnaires should be collected at the indicated timepoints whenever possible, but, since the administration of the questionnaires represents an additional procedure not included in routine clinical care, these timepoints are considered indicative only, and patients will not be recalled specifically to complete questionnaires if a routine clinical visit is not scheduled.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Italy
  • AL
    • Alessandria, AL, Italy, 15121
      • Recruiting
      • Novartis Investigative Site
  • AV
    • Avellino, AV, Italy, 83100
      • Recruiting
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Recruiting
      • Novartis Investigative Site
  • FI
    • Florence, FI, Italy, 50134
      • Recruiting
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20132
      • Recruiting
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90146
      • Recruiting
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Recruiting
      • Novartis Investigative Site
    • Roma, RM, Italy, 00168
      • Recruiting
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Recruiting
      • Novartis Investigative Site
  • VI
    • Bassano del Grappa, VI, Italy, 36061
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Italian population of adult patients with PNH either naïve to iptacopan or transitioning from the Managed Access Program (MAP) starting from January 2023

Description

Inclusion criteria:

1. signed informed consent: patient must provide written informed before any study assessment is collected; in case of deceased patients, informed consent is not required as per Art. 110, comma 1 of Legislative Decree n° 196, dated 30 June 2003 as amended by D.lgs. 101/2018 and the "Autorizzazione generale al trattamento dei dati personali effettuato per scopi di ricerca scientifica" n° 9/2016
2. Male and female,
3. ≥ 18 years of age,
4. documented diagnosis of PNH,
5. followed in Italian clinical sites,
6. on treatment with iptacopan prescribed as per routine medical care (i.e. patients naïve to treatment for whom the decision to start this treatment has already been made on the basis of clinical practice and according to SmPC and AIFA criteria and regardless of inclusion in this study or patients already treated under the Managed Access Program (MAP))

Exclusion criteria:

1.Concomitant participation in an interventional clinical study related to PNH or its treatment.

No other inclusion/exclusion criteria apply other than the requirements stated in the Summary of Product Characteristics (SmPC).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Iptacopan; Treatment with iptacopan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
absolute change in Hb level post iptacopan initiation	12-month absolute change in hemoglobin (Hb) level post iptacopan initiation	12 months
Proportion of patients with no RBC transfusions	12-month proportion of patients with no Red Blood Cells (RBC) transfusions, prescribed as per local requirement and based on Investigator's judgment, after Day 14.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Socio-demographic and clinical variables of Paroxysmal Nocturnal Hemoglobinuria population	Descriptive measures of the socio-demographic variables, proportion of PNH cells, clinical symptoms, laboratory parameters, concomitant diseases and treatments and outcomes of PNH patients at iptacopan initiation.	date of iptacopan start, day 0
Absolute change in Hb level post iptacopan initiation	24-month absolute change in Hb level post iptacopan initiation	date of iptacopan start (day 0), 24 months
Proportion of patients who didn't need RBC transfusion	24-month proportion of patients who didn't need RBC transfusion, prescribed as per local requirement and based on Investigator's judgment, post iptacopan initiation	24 months
Proportion of patients with Hb levels ≥ 12 g/dL AND no RBC transfusion	12- and 24-month proportion of patients with Hb levels ≥ 12 g/dL AND no RBC transfusion, prescribed as per local requirement and based on Investigator's judgment, between Day 14 and month 12 or month 24	12 month, 24 month
Proportion of patients with change in Hb levels ≥ 2 g/dL post iptacopan initiation AND no RBC transfusion	12- and 24-month proportion of patients with change in Hb levels ≥ 2 g/dL post iptacopan initiation AND no RBC transfusion, prescribed as per local requirement and based on Investigator's judgment, between Day 14 and month 12 or month 24	12 month, 24 month
Average number of RBC transfusion	Average number of RBC transfusion, prescribed as per local requirement and based on Investigator's judgment, per patient during 12- and 24-months post iptacopan initiation	12 months and 24 months
Percentage change in LDH level post iptacopan initiation	12- and 24-month percentage change in LDH level post iptacopan initiation.	date of iptacopan start (day 0), month 12, month 24
Change in reticulocyte count post iptacopan initiation.	12- and 24-month change in reticulocyte count post iptacopan initiation.	date of iptacopan start (day 0), month 12, month 24
Absolute change in bilirubin level post iptacopan initiation.	12- and 24-month absolute change in bilirubin level post iptacopan initiation.	date of iptacopan start (day 0), month 12, month 24
Frequency of adverse events (AE) and serious adverse events (SAE) over 12 and 24 months of follow-up	Frequency of adverse events (AE) and serious adverse events (SAE) over 12 and 24 months of follow-up post iptacopan initiation	12 months and 24 months
Proportion of BTH occurrence	Proportion of Breakthrough Hemolysis (BTH) occurrence over 12 and 24 months of follow-up post iptacopan initiation	12 months and 24 months
Type and proportion of Infections occurrence over 12 and 24 months of follow-up	Type and proportion (count and percentage) of Infections occurrence over 12 and 24 months of follow-up post iptacopan initiation	12 months and 24 months
Type and proportion of major adverse vascular events (MAVEs) occurrence	Type and proportion of major adverse vascular events (MAVEs) occurrence over 12 and 24 months of follow-up post iptacopan initiation	12 months and 24 months
Type and proportion of new comorbidities	Type and proportion of new comorbidities occurred within 12 and 24 months of follow-up post iptacopan initiation	12 months and 24 months
Type and proportion of concomitant medications newly prescribed	Type and proportion of concomitant medications newly prescribed during 12 and 24 months of follow-up post iptacopan initiation	12 months and 24 months
Absolute change in Medication Adherence Report Scale - 5 item (MARS-5) scores	The MARS-5 questionnaire is a validated self-report questionnaire developed to assess patient adherence to prescribed medication, focusing on both intentional and unintentional non-adherence. It consists of five items, each rated on a 5-point Likert Scale, from 0 ("Always") to 5 ("Never"). Items evaluate behaviors such as forgetting to take medications, altering the dose or stopping the treatment. The total score ranges from 5 to 25, with higher scores indicating better adherence to treatment.	date of iptacopan start (day 0), month 12 and month 24
Absolute change from iptacopan initiation in PROMIS-29+2 score.	The Patient-Reported Outcomes Measurement Information System (PROMIS) Profile-29+2 is a validated standardized patient reported outcome measure to assess generic health-related quality of life. The questionnaire covers the following nine health domains: Physical function, Anxiety, Depression, Fatigue, Sleep disturbance, Ability to participate in social roles and activities, Pain interference, Cognitive function and Pain intensity. The recall period for all items is the past 7 days. Each of the first eight domains is assessed through 4 items using a 5-point Likert scale. Pain intensity is measured with a single item on an 11-point numeric rating scale from 0 ("no pain") to 10 ("worst imaginable pain"). Each domain is scored separately, with T-scores used to represent the severity or level of functioning in each area. Higher scores can indicate either better health (e.g., physical function) or greater severity of symptoms (e.g., anxiety, depression).	date of iptacopan start (day 0), month 12 and month 24
Absolute change from iptacopan initiation in WPAI:SHP score.	Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a validated patient-reported outcome measure designed to assess the impact of a specific health problem on work and daily activities. In this study, the questionnaire has been customized for PNH. It includes six questions grouped into four key domains: Absenteeism (work time missed due to PNH), Presenteeism (impairment while working due to PNH), Overall work productivity loss (combined absenteeism and presenteeism), Activity impairment (impact of PNH on regular daily activities outside of work). The recall period is the past 7 days. Responses are used to calculate the percentage of work time missed and the level of impairment experienced by the patient. Higher scores represent greater impairment and reduced productivity.	date of iptacopan start (day 0), month 12 and month 24
Number of hospitalizations, emergency room visits, and hospital-based outpatient visits attributable to the management of AEs related to the study treatment	Healthcare resources utilization: The number of hospitalizations, emergency room visits, and hospital-based outpatient visits attributable to the management of adverse events (AEs) related to the study treatment will be documented.	Up to 24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: October 30, 2025
• First Submitted That Met QC Criteria: November 13, 2025
• First Posted (Actual): November 14, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NIS; PNH; paroxysmal nocturnal hemoglobinuria; REAL-CARE; ptacopan
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Hemic and Lymphatic Diseases; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: CLNP023C1IT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO