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

January 20, 2023 updated by: Alexion Pharmaceuticals

Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Leeds, United Kingdom, LS9 7TF
        • Clinical Study Site
      • London, United Kingdom, SE5 9RS
        • Clinical Study Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key 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.

Key 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Biological: 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.
Other Names:
  • Soliris
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.
Other Names:
  • Ultomiris
  • ALXN1210

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion Of Participants Who Experience Free Complement Component 5 (C5)-associated Breakthrough Hemolysis (BTH)
Time Frame: Baseline through Day 351
Baseline through Day 351

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion Of Participants Who Experience BTH
Time Frame: Baseline through Day 351
Baseline through Day 351
Hemolysis As Directly Measured By Lactate Dehydrogenase (LDH) Percent Change From Baseline To Day 351
Time Frame: Baseline, Day 351
Baseline, Day 351
Proportion Of Participants Who Receive A Transfusion
Time Frame: Baseline through Day 351
Baseline through Day 351
Proportion Of Participants With Stabilized Hemoglobin
Time Frame: Baseline through Day 351
Baseline through Day 351

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2021

Primary Completion (Actual)

December 20, 2022

Study Completion (Actual)

December 20, 2022

Study Registration Dates

First Submitted

March 23, 2020

First Submitted That Met QC Criteria

March 23, 2020

First Posted (Actual)

March 25, 2020

Study Record Updates

Last Update Posted (Actual)

January 23, 2023

Last Update Submitted That Met QC Criteria

January 20, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALXN1210-PNH-401
  • 2019-003440-74 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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