Real Life Use of Ravulizumab in Italian Patients With Paroxysmal Nocturnal Hemoglobinuria

Study Overview
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Brief Summary
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This study will collect clinical response data on participants who were already treated with eculizumab for at least 26 weeks and who started ravulizumab treatment as a specific therapeutic strategy as per ordinary clinical practice.

Detailed Description
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This study is an Italian multi-center, observational (non-interventional), cohort study composed of both retrospective and prospective observation periods on the same Paroxysmal Nocturnal Hemoglobinuria (PNH) participants. After the First Participant In from different Italian study centers, participants will be consecutively enrolled for 9 months and they will be observed for 52 weeks after the start of ravulizumab.

Official Title
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Real Life Use of Ravulizumab in Italian Patients With Paroxysmal Nocturnal Hemoglobinuria a Multicenter Observational Retrospective and Prospective Cohort Study.

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: Ravulizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight of 10 kilogram or above Hemolysis with clinical symptom(s) indicative of high disease activity Documented diagnoses of PNH confirmed by high-sensitivity flow cytometry evaluation of red blood cells and white blood cells with granulocyte or monocyte clone size of ≥ 5% Clinically stable after having been treated with eculizumab for at least the past 6 months Participant already assigned to ravulizumab treatment as a specific therapeutic strategy within the current routine clinical practice (this decision has to be made independently and before the enrolment of the participant in the study) Vaccinated against Neisseria meningitidis (according to Summary of Product Characteristics) < 3 years before dosing or at least 2 weeks prior to initiating ravulizumab unless the risk of delaying ravulizumab therapy outweighs the risk of developing a meningococcal infection Signed written informed and privacy consent prior to study participation Exclusion Criteria: History of hematopoietic stem cell transplantation (evaluated at baseline) Known pregnant or breastfeeding participant (evaluated at baseline) Participant unable to read and write in Italian language and to autonomously fill in questionnaires and scales (evaluated at enrolment) Participants enrolled in any clinical study receiving experimental treatments for PNH (evaluated at baseline) Hypersensitivity to the active substance or to any of the excipient of the study drug. Participants with unresolved N. meningitidis infection at treatment initiation Participants who are not currently vaccinated against N. meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants With PNH<br>Data will be collected on participants who were already treated with eculizumab for at least 26 weeks and who started ravulizumab treatment as per clinical practice. | Drug: Ravulizumab<br>* Participants will be observed for 52 weeks after the start of ravulizumab.<br>* Other names: Ultomiris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change In Lactate Dehydrogenase (LDH) From Baseline To End Of Observation | The analysis using descriptive statistics will be performed on the Full Analysis Set, including the participants having the LDH evaluation at both the baseline and at the end of observation. | Baseline through up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change In LDH From Baseline To End Of Observation On Participants Treated With Ravulizumab With Respect To The Observed Treatment Period With Eculizumab | The difference of percentage change in LDH from baseline to end of observation will be calculated on participants treated with ravulizumab (over the 52 weeks after baseline) and on the same participants treated with eculizumab (during up to 52 weeks before baseline). | Baseline through up to Week 52 | 
| Number of Transfusions During Treatment Period With Ravulizumab | The number of participants who needed transfusions, with relative frequency and percentage, and descriptive statistics on the total number of transfusions (number of packed red blood cell units transfused) will be calculated for both the treatment period with ravulizumab and the treatment period with eculizumab. | Baseline through up to Week 52 | 
| Total Number Of Transfusion Sessions During The Treatment Period With Ravulizumab | The number of participants who needed transfusions, with relative frequency and percentage, and descriptive statistics on the number of transfusion sessions (number of days) will be calculated for both the treatment period with ravulizumab and the treatment period with eculizumab. | Baseline through up to Week 52 | 
| Number Of Participants Undergoing Ravulizumab Without A ≥ 2 gram/deciliter (g/dL) Decrease In Hemoglobin Level In The Absence Of Transfusion | The proportion of participants without a ≥ 2 g/dL decrease in hemoglobin level in the absence of transfusion will be calculated for both the treatment period with ravulizumab and the treatment period with eculizumab. | Baseline through up to Week 52 | 
| Breakthrough Hemolysis (BTH) In The Presence Of Elevated LDH During Treatment Period With Ravulizumab | BTH is defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin < 10 g/dL], major adverse vascular event including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥ 2 * upper limit of normal (ULN) after prior LDH reduction to < 1.5 * ULN while on therapy. | Baseline through up to Week 52 | 
| Change From Baseline To Each Timepoint Of Assessment Using Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale | The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Participants will score each item on a 5-point scale. Total scores range from 0 to 52, with a higher score indicating better Quality of Life (QoL). | Baseline through up to Week 52 | 
| Change From Baseline To Each Timepoint Of Assessment Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 Scale | EORTC is a questionnaire developed to assess the QoL of cancer participants over the preceding 7 days. The questionnaire has 30 questions related to QoL, with the first 28 questions scored on a 4-point scale and the final 2 questions that probe the participant's overall health and QoL scored on a scale of 1 (very poor) to 7 (excellent). Each subscale has a range of 0 to 100%. Thus, a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem. | Baseline through up to Week 52 | 
| PNH-specific Patient Preference Questionnaire (PPQ) | PNH-PPQ is a participant-centered approach for evaluating preferences for the treatment of PNH. It contains 11 questions assessing overall treatment preference, evaluating treatment preference according to 9 treatment characteristics, assessing the most important treatment characteristic for participant overall medication preference, and evaluating those same aspects of treatment with ravulizumab. | Week 52 | 
| Number of Participants Experiencing Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs that will occur during the ravulizumab treatment will be collected and will be reported to the Investigator or qualified designee by the participant. | Baseline through up to Week 52 | 
| Costs Related to PNH Sustained By National Health System (NHS) For Ravulizumab Treatment | The following medical costs related to PNH sustained by NHS will be collected: specialist visits, pharmacological and non-pharmacological treatments, hospital and emergency rooms admissions, and examinations (by examination type). This will be reported through descriptive statistics and will be appraised considering the quantity of resource consumption by medical resources and its unit costs. | Baseline, Weeks 18, 34, and 52 | 
| Costs Sustained By The Participants Related To The Infusion Visits For Ravulizumab Treatment | The following costs sustained by the participants related to the infusion visits will be collected: average cost to reach the structure, overall time required for the infusion (time to reach the structure + time of infusion), retirement status of the participant, loss of working days, and need of a caregiver. This will be calculated in terms of the total cost of transport and overall time required for infusion. | Baseline, Weeks 18, 34, and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PIGA Gene, Complement-inhibitor Protein, CD55, CD59, Efficacy, Safety, Patient Registry