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

NCT ID: NCT04320602

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-14
• Study Completion Date: 2022-12-20

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).

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ravulizumab

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).

Group Type: EXPERIMENTAL

Eculizumab

Intervention Type: BIOLOGICAL

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.

Ravulizumab

Intervention Type: BIOLOGICAL

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.

Interventions

Eculizumab

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

Ravulizumab

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Soliris; ALXN1210; Ultomiris

Eligibility Criteria

Inclusion Criteria

1. 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%.

2. Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.

3. LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.

4. 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.

5. Body weight ≥ 40 kilograms.

Exclusion Criteria

1. History of major adverse vascular events within 6 months of Day 1.

2. History of bone marrow transplantation.

3. 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.

4. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.

5. 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

6. Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.

7. More than 1 LDH value > 2 × ULN within the 6 months prior to Day 1.

8. Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening.

9. Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Study Site

Leeds, , United Kingdom

Research Site

Leeds, , United Kingdom

Clinical Study Site

London, , United Kingdom

Research Site

London, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=ALXN1210-PNH-401&amp;attachmentIdentifier=f4f63037-1e40-4456-96df-06b466412244&amp;fileName=ALXN1210-PNH-401-_CSR_synopsis_redacted.pdf&amp;versionIdentifier=

Related Info

Other Identifiers

2019-003440-74

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALXN1210-PNH-401

Identifier Type: -

Identifier Source: org_study_id