A Real World Effectiveness Study of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study Overview
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Brief Summary
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This is a 24-month multicenter, observational study designed to describe the real world effectiveness of pegcetacoplan in patients with PNH. Patients meeting the eligibility criteria will be enrolled in the study at the enrollment visit and followed prospectively for 24 (+/- 3) months. The scope of the study is to collect both retrospective and prospective data. The main part of the study will be prospective,collecting data on effectiveness, safety, patient- and clinician-reported outcomes and health care resource use.

Detailed Description
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As pegcetacoplan is a new product on the market, with a new mechanism of action, there is an urgent need to provide data to treaters, payers and the PNH community on the real-world usage and effectiveness of pegcetacoplan. This study aims to fill part of that knowledge gap and to add to the knowledge base regarding the use of pegcetacoplan in routine medical practice. Another important rationale for this study is to provide information on pre and post pegcetacoplan treatment outcomes. The study plans to include approximately 200 patients at 70 sites in Europe, Middle East, Canada and Australia. Patients meeting the eligibility criteria will be enrolled in the study at the enrollment visit and followed prospectively for 24 (+/- 3) months. Patients will come to their routine visits and the available data from each visit will be collected. The scope of the study is to collect both retrospective and prospective data. The main part of the study will be prospective, collecting data on effectiveness, safety, patient- and clinician-reported outcomes and health care resource use. The study will also collect retrospective data before pegcetacoplan treatment start, which will consist of information on PNH treatment, blood transfusions and healthcare resource use. Data will be collected for up to 12 months prior to pegcetacoplan treatment start. As patients may have been treated with pegcetacoplan for up to 12 months prior to enrollment, retrospective data may be collected for up to 24 months. This means that the total data collection period including both the retrospective and the prospective part is up to 48 (+/- 3) months.

Official Title
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A Single Arm, Multicentre Observational Study to Evaluate Effectiveness of Pegcetacoplan Under Real World Conditions in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: Pegcetacoplan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years of age with a documented PNH diagnosis. Patient started routine treatment with pegcetacoplan for PNH up to 12 months before enrollment or prescribed pegcetacoplan at enrollment. Decision to initiate treatment shall be made by the treating physician and independently from the decision to include the patient in the study. Patient is willing and able to provide written informed consent to participate in the study in a manner approved by the Institutional Review Board/Independent Ethics Committee and local regulations. Exclusion Criteria: Enrollment in a concurrent clinical interventional study, or intake of an Investigational Medicinal Product (IMP), within three months prior to the start of the current pegcetacoplan treatment. Initiated current treatment with pegcetacoplan in an interventional study.

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

| Intervention/Treatment |
| --- |
|Drug: Pegcetacoplan|Pegcetacoplan will be prescribed according to the label in patients with PNH.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in observed hemoglobin level from initiation of treatment with pegcetacoplan to 6 months | Hemoglobin level in g/dL. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Lactate Dehydrogenase values from initiation of pegcetacoplan treatment to 6 months | Lactate Dehydrogenase (LDH) in U/L | 6 months | 
| Change in Absolute Reticulocyte Count (ARC) from initiation of pegcetacoplan treatment to 6 months | Absolute Reticulocyte Count (ARC) in 10^9/L | 6 months | 
| Change in indirect/ total bilirubin from initiation of pegcetacoplan treatment to 6 months | Indirect/ total bilirubin in umol/L | 6 months | 
| Change in Haptoglobin from initiation of pegcetacoplan treatment to 6 months | Haptoglobin in mg/dL | 6 months | 
| Change in Ferritin from initiation of pegcetacoplan treatment to 6 months | Ferritin in ug/L | 6 months | 
| Hemoglobin at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 6 months | 
| Hemoglobin at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 12 months | 
| Hemoglobin at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 18 months | 
| Hemoglobin at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 24 months | 
| Lactate Dehydrogenase at initiation of pegcetacoplan treatment and each 6 months until end of study | Lactate Dehydrogenase (LDH) in U/L | 6 months | 
| Lactate Dehydrogenase at initiation of pegcetacoplan treatment and each 6 months until end of study | Lactate Dehydrogenase (LDH) in U/L | 12 months | 
| Lactate Dehydrogenase at initiation of pegcetacoplan treatment and each 6 months until end of study | Lactate Dehydrogenase (LDH) in U/L | 18 months | 
| Lactate Dehydrogenase at initiation of pegcetacoplan treatment and each 6 months until end of study | Lactate Dehydrogenase (LDH) in U/L | 24 months | 
| Absolute Reticulocyte Count at initiation of pegcetacoplan treatment and each 6 months until end of study | Absolute Reticulocyte Count (ARC) in 10^9/L | 6 months | 
| Absolute Reticulocyte Count at initiation of pegcetacoplan treatment and each 6 months until end of study | Absolute Reticulocyte Count (ARC) in 10^9/L | 12 months | 
| Absolute Reticulocyte Count at initiation of pegcetacoplan treatment and each 6 months until end of study | Absolute Reticulocyte Count (ARC) in 10^9/L | 18 months | 
| Absolute Reticulocyte Count at initiation of pegcetacoplan treatment and each 6 months until end of study | Absolute Reticulocyte Count (ARC) in 10^9/L | 24 months | 
| Indirect/ total bilirubin at initiation of pegcetacoplan treatment and each 6 months until end of study | Indirect/ total bilirubin in umol/L | 6 months | 
| Indirect/ total bilirubin at initiation of pegcetacoplan treatment and each 6 months until end of study | Indirect/ total bilirubin in umol/L | 12 months | 
| Indirect/ total bilirubin at initiation of pegcetacoplan treatment and each 6 months until end of study | Indirect/ total bilirubin in umol/L | 18 months | 
| Indirect/ total bilirubin at initiation of pegcetacoplan treatment and each 6 months until end of study | Indirect/ total bilirubin in umol/L | 24 months | 
| Haptoglobin at initiation of pegcetacoplan treatment and each 6 months until end of study | Haptoglobin in mg/dL | 6 months | 
| Haptoglobin at initiation of pegcetacoplan treatment and each 6 months until end of study | Haptoglobin in mg/dL | 12 months | 
| Haptoglobin at initiation of pegcetacoplan treatment and each 6 months until end of study | Haptoglobin in mg/dL | 18 months | 
| Haptoglobin at initiation of pegcetacoplan treatment and each 6 months until end of study | Haptoglobin in mg/dL | 24 months | 
| Ferritin at initiation of pegcetacoplan treatment and each 6 months until end of study | Ferritin in ug/L | 6 months | 
| Ferritin at initiation of pegcetacoplan treatment and each 6 months until end of study | Ferritin in ug/L | 12 months | 
| Ferritin at initiation of pegcetacoplan treatment and each 6 months until end of study | Ferritin in ug/L | 18 months | 
| Ferritin at initiation of pegcetacoplan treatment and each 6 months until end of study | Ferritin in ug/L | 24 months | 
| Hemoglobin ≥ 12 g/dL at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 6 months | 
| Hemoglobin ≥ 12 g/dL at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 12 months | 
| Hemoglobin ≥ 12 g/dL at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 18 months | 
| Hemoglobin ≥ 12 g/dL at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 24 months | 
| Increase in hemoglobin levels of ≥ 2 g/dL at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 6 months | 
| Increase in hemoglobin levels of ≥ 2 g/dL at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 12 months | 
| Increase in hemoglobin levels of ≥ 2 g/dL at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 18 months | 
| Increase in hemoglobin levels of ≥ 2 g/dL at initiation of pegcetacoplan treatment and each 6 months until end of study | Hemoglobin in g/dL | 24 months | 
| Acute hemolytic event requiring additional intervention at initiation of pegcetacoplan treatment and each 6 months until end of study | Yes/No | 6 months | 
| Acute hemolytic event requiring additional intervention at initiation of pegcetacoplan treatment and each 6 months until end of study | Yes/No | 12 months | 
| Acute hemolytic event requiring additional intervention at initiation of pegcetacoplan treatment and each 6 months until end of study | Yes/No | 18 months | 
| Acute hemolytic event requiring additional intervention at initiation of pegcetacoplan treatment and each 6 months until end of study | Yes/No | 24 months | 
| Annualized number of red blood cell (RBC) transfusions during pegcetacoplan treatment until end of study compared to the 12 month period before pegcetacoplan treatment | Total number of RBC transfusions | 12 months | 
| Annualized number of red blood cell (RBC) units during pegcetacoplan treatment until end of study compared to the 12 month period before pegcetacoplan treatment | Total number of RBC units | 12 months | 
| Fatigue at initiation of treatment with pegcetacoplan and every 6 months until end of study | Patient reported outcome scale scores for the Functional assessment of chronic illness therapy (FACIT) - Fatigue. It is a 13-item scale and each item is scored on a 5-point Likert Scale ranging from 0-Not at all to 4-Very much. The FACIT-fatigue score is obtained by summing all item scores. The score range from 0 to 52, higher score indicating less fatigue and lower score indicating more fatigue. | 6 months | 
| Fatigue at initiation of treatment with pegcetacoplan and every 6 months until end of study | Patient reported outcome scale scores for the Functional assessment of chronic illness therapy (FACIT) - Fatigue. It is a 13-item scale and each item is scored on a 5-point Likert Scale ranging from 0-Not at all to 4-Very much. The FACIT-fatigue score is obtained by summing all item scores. The score range from 0 to 52, higher score indicating less fatigue and lower score indicating more fatigue. | 12 months | 
| Fatigue at initiation of treatment with pegcetacoplan and every 6 months until end of study | Patient reported outcome scale scores for the Functional assessment of chronic illness therapy (FACIT) - Fatigue. It is a 13-item scale and each item is scored on a 5-point Likert Scale ranging from 0-Not at all to 4-Very much. The FACIT-fatigue score is obtained by summing all item scores. The score range from 0 to 52, higher score indicating less fatigue and lower score indicating more fatigue. | 18 months | 
| Fatigue at initiation of treatment with pegcetacoplan and every 6 months until end of study | Patient reported outcome scale scores for the Functional assessment of chronic illness therapy (FACIT) - Fatigue. It is a 13-item scale and each item is scored on a 5-point Likert Scale ranging from 0-Not at all to 4-Very much. The FACIT-fatigue score is obtained by summing all item scores. The score range from 0 to 52, higher score indicating less fatigue and lower score indicating more fatigue. | 24 months | 
| Quality of life at initiation of treatment with pegcetacoplan and every 6 months until end of study | Patient reported outcome scale scores for Quality of life questionnaire for patients with Aplastic Anemia and/or Paroxysmal Nocturnal Hemoglobinuria (QLQ AA/PNH). The QLQ AA/PNH questionnaire consists of 54 items relating to how the patient has been feeling lately with 4 response options: 'Not at all', 'A little', 'Moderately' and 'Very'. Scoring guidelines that have been validated for use in clinical studies will be used to calculate patients' scores. | 6 months | 
| Quality of life at initiation of treatment with pegcetacoplan and every 6 months until end of study | Patient reported outcome scale scores for Quality of life questionnaire for patients with Aplastic Anemia and/or Paroxysmal Nocturnal Hemoglobinuria (QLQ AA/PNH). The QLQ AA/PNH questionnaire consists of 54 items relating to how the patient has been feeling lately with 4 response options: 'Not at all', 'A little', 'Moderately' and 'Very'. Scoring guidelines that have been validated for use in clinical studies will be used to calculate patients' scores. | 12 months | 
| Quality of life at initiation of treatment with pegcetacoplan and every 6 months until end of study | Patient reported outcome scale scores for Quality of life questionnaire for patients with Aplastic Anemia and/or Paroxysmal Nocturnal Hemoglobinuria (QLQ AA/PNH). The QLQ AA/PNH questionnaire consists of 54 items relating to how the patient has been feeling lately with 4 response options: 'Not at all', 'A little', 'Moderately' and 'Very'. Scoring guidelines that have been validated for use in clinical studies will be used to calculate patients' scores. | 18 months | 
| Quality of life at initiation of treatment with pegcetacoplan and every 6 months until end of study | Patient reported outcome scale scores for Quality of life questionnaire for patients with Aplastic Anemia and/or Paroxysmal Nocturnal Hemoglobinuria (QLQ AA/PNH). The QLQ AA/PNH questionnaire consists of 54 items relating to how the patient has been feeling lately with 4 response options: 'Not at all', 'A little', 'Moderately' and 'Very'. Scoring guidelines that have been validated for use in clinical studies will be used to calculate patients' scores. | 24 months | 
| Health care resource use: Annualized number of hospitalizations and emergency room visits during pegcetacoplan treatment until end of study compared to the 12-month period before pegcetacoplan treatment. | Number of hospitalizations and emergency room visits | 12 months | 
| Patient treatment satisfaction every 6 months until end of study | Patient treatment satisfaction (1-5 point scale), 5=highly satisfied, 1= highly dissatisfied | 6 months | 
| Patient treatment satisfaction every 6 months until end of study | Patient treatment satisfaction (1-5 point scale), 5=highly satisfied, 1= highly dissatisfied | 12 months | 
| Patient treatment satisfaction every 6 months until end of study | Patient treatment satisfaction (1-5 point scale), 5=highly satisfied, 1= highly dissatisfied | 18 months | 
| Patient treatment satisfaction every 6 months until end of study | Patient treatment satisfaction (1-5 point scale), 5=highly satisfied, 1= highly dissatisfied | 24 months | 
| Physician treatment satisfaction every 6 months until end of study | Physician treatment satisfaction (1-5 point scale), 5=highly satisfied, 1= highly dissatisfied | 6 months | 
| Physician treatment satisfaction every 6 months until end of study | Physician treatment satisfaction (1-5 point scale), 5=highly satisfied, 1= highly dissatisfied | 12 months | 
| Physician treatment satisfaction every 6 months until end of study | Physician treatment satisfaction (1-5 point scale), 5=highly satisfied, 1= highly dissatisfied | 18 months | 
| Physician treatment satisfaction every 6 months until end of study | Physician treatment satisfaction (1-5 point scale), 5=highly satisfied, 1= highly dissatisfied | 24 months |