Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
Primary Purpose
Paroxysmal Nocturnal Hemoglobinuria
Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Eculizumab
Ravulizumab
Sponsored by
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring Paroxysmal Nocturnal Hemoglobinuria, PNH, Ravulizumab, Ultomiris, Eculizumab, Soliris
Eligibility Criteria
Key Inclusion Criteria:
- Documented diagnosis 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%.
- Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
- LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
- To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infections within 3 years prior to initiating study drug.
- Body weight ≥ 40 kilograms.
Key Exclusion Criteria:
- History of major adverse vascular events within 6 months of Day 1.
- History of bone marrow transplantation.
- Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.
Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening:
- Erythropoietin or immunosuppressants for at least 8 weeks
- Systemic corticosteroids for at least 4 weeks
- Vitamin K antagonists (for example, warfarin) with a stable international normalized ratio level for at least 4 weeks
- Iron supplements or folic acid for 4 weeks
- Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
- More than 1 LDH value > 2 × ULN within the 6 months prior to Day 1.
- Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening.
- Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.
Sites / Locations
- Clinical Study Site
- Clinical Study Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ravulizumab
Arm Description
Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days).
Outcomes
Primary Outcome Measures
Proportion Of Participants Who Experience Free Complement Component 5 (C5)-associated Breakthrough Hemolysis (BTH)
Secondary Outcome Measures
Proportion Of Participants Who Experience BTH
Hemolysis As Directly Measured By Lactate Dehydrogenase (LDH) Percent Change From Baseline To Day 351
Proportion Of Participants Who Receive A Transfusion
Proportion Of Participants With Stabilized Hemoglobin
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04320602
Brief Title
Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
Official Title
Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
March 26, 2021 (Actual)
Primary Completion Date
December 20, 2022 (Actual)
Study Completion Date
December 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria
Keywords
Paroxysmal Nocturnal Hemoglobinuria, PNH, Ravulizumab, Ultomiris, Eculizumab, Soliris
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ravulizumab
Arm Type
Experimental
Arm Description
Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days).
Intervention Type
Biological
Intervention Name(s)
Eculizumab
Other Intervention Name(s)
Soliris
Intervention Description
Participants must have been prescribed and be receiving a stable dose of eculizumab 1200 milligrams (mg) every 2 weeks (q2w) for at least 3 months prior to the Screening Period. During the Screening Period, participants will continue to receive eculizumab 1200 mg q2w.
Intervention Type
Biological
Intervention Name(s)
Ravulizumab
Other Intervention Name(s)
ALXN1210, Ultomiris
Intervention Description
During the Treatment Period, participants will receive a loading dose of ravulizumab on Day 1, followed by maintenance doses on Day 15 and every 8 weeks, administered by intravenous infusion. Ravulizumab loading and maintenance doses will be based on participants' body weight per approved dose regimen.
Primary Outcome Measure Information:
Title
Proportion Of Participants Who Experience Free Complement Component 5 (C5)-associated Breakthrough Hemolysis (BTH)
Time Frame
Baseline through Day 351
Secondary Outcome Measure Information:
Title
Proportion Of Participants Who Experience BTH
Time Frame
Baseline through Day 351
Title
Hemolysis As Directly Measured By Lactate Dehydrogenase (LDH) Percent Change From Baseline To Day 351
Time Frame
Baseline, Day 351
Title
Proportion Of Participants Who Receive A Transfusion
Time Frame
Baseline through Day 351
Title
Proportion Of Participants With Stabilized Hemoglobin
Time Frame
Baseline through Day 351
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Documented diagnosis 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%.
Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infections within 3 years prior to initiating study drug.
Body weight ≥ 40 kilograms.
Key Exclusion Criteria:
History of major adverse vascular events within 6 months of Day 1.
History of bone marrow transplantation.
Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.
Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening:
Erythropoietin or immunosuppressants for at least 8 weeks
Systemic corticosteroids for at least 4 weeks
Vitamin K antagonists (for example, warfarin) with a stable international normalized ratio level for at least 4 weeks
Iron supplements or folic acid for 4 weeks
Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
More than 1 LDH value > 2 × ULN within the 6 months prior to Day 1.
Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening.
Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.
Facility Information:
Facility Name
Clinical Study Site
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Clinical Study Site
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
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