Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab

NCT ID: NCT03748823

Last Updated: 2024-09-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

139 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-19

Study Completion Date

2023-08-31

Brief Summary

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The primary objective of this study is to evaluate pharmacokinetics (PK) of ravulizumab administered subcutaneously via an on-body delivery system (OBDS) compared with intravenously administered ravulizumab in adult participants with PNH who are clinically stable on eculizumab for at least 3 months prior to study entry.

Detailed Description

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The study will consist of up to a 30-day Screening Period, a 10-week Randomized Treatment Period, and an Extension Period of up to 172 weeks.

Conditions

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Paroxysmal Nocturnal Hemoglobinuria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ravulizumab SC Treatment Group

In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by SC maintenance doses of ravulizumab administered via the ravulizumab OBDS on Day 15 and every week (qw) thereafter for a total of 10 weeks of study treatment.

In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.

Group Type EXPERIMENTAL

Ravulizumab OBDS

Intervention Type COMBINATION_PRODUCT

The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.

Ravulizumab

Intervention Type BIOLOGICAL

Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.

Ravulizumab IV Treatment Group

In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by IV maintenance doses of ravulizumab on Day 15.

In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.

Group Type ACTIVE_COMPARATOR

Ravulizumab OBDS

Intervention Type COMBINATION_PRODUCT

The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.

Ravulizumab

Intervention Type BIOLOGICAL

Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.

Interventions

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Ravulizumab OBDS

The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.

Intervention Type COMBINATION_PRODUCT

Ravulizumab

Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.

Intervention Type BIOLOGICAL

Other Intervention Names

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ALXN1210

Eligibility Criteria

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Inclusion Criteria

* Male or female ≥18 years of age
* Treated with eculizumab for PNH for at least 3 months prior to Day 1
* LDH level ≤1.5 × upper limit of normal (ULN) at screening
* PNH diagnosis confirmed by documented high-sensitivity flow cytometry.
* Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
* Body weight ≥40 to \<100 kilogram (kg)
* Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
* Willing and able to give written informed consent and comply with study visit schedule.

Exclusion Criteria

* More than 1 LDH value \> 2 × ULN within the 3 months prior to study entry
* History of bone marrow transplantation.
* History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the Investigator or Sponsor, would preclude participation.
* Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).
* Females who are pregnant, breastfeeding or who have a positive pregnancy test at screening or Day 1.
* Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Los Angeles, California, United States

Site Status

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Liverpool, , Australia

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Parkville, , Australia

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Vienna, , Austria

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Antwerp, , Belgium

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Brussels, , Belgium

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Hasselt, , Belgium

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Leuven, , Belgium

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Botucatu, , Brazil

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Ribeirão Preto, , Brazil

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Rio de de Janeiro, , Brazil

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Salvador, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Toronto, Ontario, Canada

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Helsinki, , Finland

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Amiens, , France

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Brest, , France

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Lille, , France

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Montpellier, , France

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Nantes, , France

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Nice, , France

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Paris, , France

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Pessac, , France

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Pierre-Bénite, , France

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Poitiers, , France

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Rennes, , France

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Strasbourg, , France

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Tours, , France

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Catania, , Italy

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Milan, , Italy

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Roma, , Italy

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Rome, , Italy

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Maastricht, , Netherlands

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Yekaterinburg, , Russia

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Badalona, , Spain

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Barcelona, , Spain

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Donostia / San Sebastian, , Spain

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Las Palmas de Gran Canaria, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Seville, , Spain

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Uppsala, , Sweden

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Adana, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Countries

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United States Australia Austria Belgium Brazil Canada Finland France Italy Netherlands Russia Spain Sweden Turkey (Türkiye)

References

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Yenerel MN, Sicre de Fontbrune F, Piatek C, Sahin F, Fureder W, Ortiz S, Ogawa M, Ozol-Godfrey A, Sierra JR, Szer J. Phase 3 Study of Subcutaneous Versus Intravenous Ravulizumab in Eculizumab-Experienced Adult Patients with PNH: Primary Analysis and 1-Year Follow-Up. Adv Ther. 2023 Jan;40(1):211-232. doi: 10.1007/s12325-022-02339-3. Epub 2022 Oct 22.

Reference Type DERIVED
PMID: 36272026 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-002370-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALXN1210-PNH-303

Identifier Type: -

Identifier Source: org_study_id

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