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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

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

NCT ID

NCT04320602

First Posted

March 23, 2020

Last Updated

January 20, 2023

Sponsor

Alexion

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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

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

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

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

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Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab

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