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

NCT03748823 | Completed Phase 3 Results FDA Drug FDA Device

• 2 other identifiers: ALXN1210-PNH-3032017-002370-39
• Study Type: interventional
• Target: 139
• Locations: 13 countries
• Sites: 49

Brief Summary

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

PNH

Outcome Measures

Primary Outcomes (1)

• Ctrough Serum Concentration of Ravulizumab

  Predose at Day 71

Secondary Outcomes (15)

• Ctrough Serum Concentration of Ravulizumab at Day 351

  Predose at Day 351

• Free Serum Complement Component 5 (C5) Concentrations at Day 71

  Predose at Day 71

• Free Serum Complement Component 5 (C5) Concentrations at Day 351

  Predose at Day 351

• Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71

  Baseline, Day 71

• Percent Change From Baseline in LDH Levels at Day 351

  Baseline, Day 351

Study Arms (2)

Ravulizumab SC Treatment Group

EXPERIMENTAL

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.

Combination Product: Ravulizumab OBDS; Biological: Ravulizumab

Ravulizumab IV Treatment Group

ACTIVE COMPARATOR

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.

Combination Product: Ravulizumab OBDS; Biological: Ravulizumab

Interventions

Ravulizumab OBDS 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 IV Treatment Group; Ravulizumab SC Treatment Group

Ravulizumab BIOLOGICAL

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

Also known as: ALXN1210

Ravulizumab IV Treatment Group; Ravulizumab SC Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (51)

Research Site

Los Angeles, California, 90089, United States

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Liverpool, 2170, Australia

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Parkville, 3050, Australia

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Vienna, 1090, Austria

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Antwerp, 2020, Belgium

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Brussels, 1200, Belgium

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Hasselt, 3500, Belgium

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Leuven, 3000, Belgium

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Botucatu, 18618-970, Brazil

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Ribeirão Preto, 14049-901, Brazil

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Rio de de Janeiro, 20211030, Brazil

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Salvador, 40170010, Brazil

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São Paulo, 01308-050, Brazil

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São Paulo, 05403-000, Brazil

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Toronto, Ontario, M5G 2C4, Canada

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Helsinki, 00029, Finland

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Amiens, 80054, France

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Brest, 29609, France

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Lille, 59037, France

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Montpellier, 34090, France

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Nantes, 44093, France

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Nice, 6200, France

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Paris, 75010, France

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Pessac, F-33604, France

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Pierre-Bénite, 69495, France

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Poitiers, 86021, France

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Rennes, 35033, France

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Strasbourg, 67098, France

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Tours, 37044, France

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Catania, 95123, Italy

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Milan, 20122, Italy

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Roma, 00168, Italy

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Rome, 161, Italy

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Maastricht, 6229 HX, Netherlands

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Moscow, 125167, Russia

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Moscow, 125284, Russia

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Saint Petersburg, 197089, Russia

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Yekaterinburg, 620102, Russia

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Badalona, 8916, Spain

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Barcelona, 08036, Spain

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Donostia / San Sebastian, 20014, Spain

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Las Palmas de Gran Canaria, 35020, Spain

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Madrid, 28040, Spain

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Majadahonda, 28222, Spain

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Seville, 41013, Spain

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Uppsala, 75185, Sweden

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Adana, 01330, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Istanbul, 34096, Turkey (Türkiye)

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Istanbul, 34899, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Related Publications (1)

• 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.

  PMID: 36272026 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

ravulizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Limitations and Caveats

To ensure the quality of the study results, all 7 participants from a noncompliant investigative site were excluded from all prespecified analysis sets due to important source documentation deviations.

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 21, 2018
• Study Start: February 19, 2019
• Primary Completion: February 2, 2021
• Study Completion: August 31, 2023
• Last Updated: September 19, 2024
• Results First Posted: October 20, 2022

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (6); CA (1); RU (4); TU (5); AU (1); IT (4); ES (7); BE (4); FI (1); SE (1); FR (13); US (1); NL (1)