A Long-term Safety and Efficacy Study of Danicopan as an Add-on Therapy to Complement Component 5 Inhibitor (C5i) in Participants With PNH

Study Overview
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Brief Summary
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This is a single-arm long-term extension study that will enroll participants with PNH who have completed participation in Alexion-sponsored clinical studies with danicopan as an add on therapy to a C5i.

Detailed Description
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The total duration of the study will be up to 3 years. Eligible participants must complete all study assessments on the parent protocol before starting this study. All participants entering this study will receive danicopan as an add-on to a background C5i therapy. The only allowed C5i therapies are eculizumab and ravulizumab.

Official Title
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A Long-term Extension (LTE) Study to Characterize the Safety and Efficacy of Danicopan as an Add-on Therapy to a Complement Component 5 Inhibitor (C5i) in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Previously Treated With Danicopan in an Alexion-sponsored Clinical Study

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: Danicopan


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: All participants who completed their participation in an Alexion sponsored clinical study with danicopan as an add on to a C5i treatment. Patient is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. Documentation of vaccination for Neisseria meningitidis: All participants must be revaccinated as per national vaccination guidelines or local practice for vaccination use with complement inhibitors. Key Exclusion Criteria: Any medical condition (for example, cardiac, pulmonary, renal, oncologic, or psychiatric) that, in the opinion of the Investigator, might interfere with participation in the study, pose any added risk to the participant, or confound the assessment of the participant. Patient has been permanently discontinued from danicopan in the parent study for any reason other than enrollment into this LTE study. Female participants who are pregnant, breastfeeding, or intending to conceive during the course of the 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Danicopan<br>Participants will receive their last dose of danicopan from the parent study the night prior to Day 1 of this LTE study and will continue daily treatment with danicopan together with their background C5i therapy. | Drug: Danicopan<br>* Oral tablet<br>* Other names: ALXN2040, ACH-0144471;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Experiencing Treatment-emergent Adverse Events (TEAEs) And Serious TEAEs |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change In Hemoglobin Values |  | Up to 3 years | 
| Proportion of patients with Hgb increase ≥ 2g/dL in the absence of transfusion over time |  | Up to 3 years | 
| Change In Absolute Reticulocyte Count |  | Up to 3 years | 
| Change In Lactate Dehydrogenase (LDH) |  | Up to 3 years | 
| Proportion Of Participants With LDH ≤ 1.5 × Upper Limit Of Normal |  | Up to 3 years | 
| Proportion Of Participants With Transfusion Avoidance |  | Up to 3 years | 
| Change In Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores | Total scores range from 0 to 52, with higher scores indicating better QoL. | Up to 3 years | 
| Change In The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 Scale (QLQ-C30) Scores | Thirty questions related to QoL, with the first 28 questions scored on a 4-point scale (1 = not at all to 4 = very much) 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). | Up to 3 years | 
| Participants Experiencing TEAEs Leading To Discontinuation |  | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paroxysmal Nocturnal Hemoglobinuria (PNH), Extravascular Hemolysis (EVH), Factor D inhibitor, Complement, Danicopan, ALXN2040, C5 inhibitor