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Paroxysmal Nocturnal HemoglobinuriaPhase 3NCT03748823

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

A Phase 3 study testing Ravulizumab OBDS and Ravulizumab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Alexion Pharmaceuticals, Inc. at 51 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Paroxysmal Nocturnal Hemoglobinuria
What is being tested?
Ravulizumab OBDS and Ravulizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
139 participants
Where
51 sitesin 14 countries
Study dates
19 Feb 2019to 31 Aug 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

51 sites in 14 countries.

51 sites in 14 countries

France13 sites
  • Research Site

    Amiens, 80054

  • Research Site

    Brest, 29609

  • Research Site

    Lille, 59037

  • Research Site

    Montpellier, 34090

  • Research Site

    Nantes, 44093

  • Research Site

    Nice, 6200

  • Research Site

    Paris, 75010

  • Research Site

    Pessac, F-33604

  • Research Site

    Pierre-Bénite, 69495

  • Research Site

    Poitiers, 86021

  • Research Site

    Rennes, 35033

  • Research Site

    Strasbourg, 67098

  • Research Site

    Tours, 37044

Other trials in France

Spain7 sites
  • Research Site

    Badalona, 8916

  • Research Site

    Barcelona, 08036

  • Research Site

    Donostia / San Sebastian, 20014

  • Research Site

    Las Palmas de Gran Canaria, 35020

  • Research Site

    Madrid, 28040

  • Research Site

    Majadahonda, 28222

  • Research Site

    Seville, 41013

Other trials in Spain

Brazil6 sites
  • Research Site

    Botucatu, 18618-970

  • Research Site

    Ribeirão Preto, 14049-901

  • Research Site

    Rio de de Janeiro, 20211030

  • Research Site

    Salvador, 40170010

  • Research Site

    São Paulo, 01308-050

  • Research Site

    São Paulo, 05403-000

Other trials in Brazil

Turkey (Türkiye)5 sites
  • Research Site

    Adana, 01330

  • Research Site

    Istanbul, 34093

  • Research Site

    Istanbul, 34096

  • Research Site

    Istanbul, 34899

  • Research Site

    Izmir, 35100

Other trials in Turkey (Türkiye)

Belgium4 sites
  • Research Site

    Antwerp, 2020

  • Research Site

    Brussels, 1200

  • Research Site

    Hasselt, 3500

  • Research Site

    Leuven, 3000

Other trials in Belgium

Italy4 sites
  • Research Site

    Catania, 95123

  • Research Site

    Milan, 20122

  • Research Site

    Roma, 00168

  • Research Site

    Rome, 161

Other trials in Italy

Russia4 sites
  • Research Site

    Moscow, 125167

  • Research Site

    Moscow, 125284

  • Research Site

    Saint Petersburg, 197089

  • Research Site

    Yekaterinburg, 620102

Other trials in Russia

Australia2 sites
  • Research Site

    Liverpool, 2170

  • Research Site

    Parkville, 3050

Other trials in Australia

United States1 site
  • Research Site

    Los Angeles, California, 90089

Other trials in United States

Austria1 site
  • Research Site

    Vienna, 1090

Other trials in Austria

Canada1 site
  • Research Site

    Toronto, Ontario, M5G 2C4

Other trials in Canada

Finland1 site
  • Research Site

    Helsinki, 00029

Other trials in Finland

Netherlands1 site
  • Research Site

    Maastricht, 6229 HX

Other trials in Netherlands

Sweden1 site
  • Research Site

    Uppsala, 75185

Other trials in Sweden

About this study

Official title: A Phase 3, Randomized, Parallel-Group, Multicenter, Open-Label, Pharmacokinetic, Noninferiority Study of Ravulizumab Administered Subcutaneously Versus Intravenously in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With Eculizumab

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.

Read the detailed description

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.

Being tested
Ravulizumab OBDS, Ravulizumab
Keywords
PNH
Medical subject headings
Hemoglobinuria, Paroxysmal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ravulizumab OBDSCombination product

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

  • RavulizumabBiological

    Also called ALXN1210

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

Study groups in NCT03748823
Study groupRoleWhat they receive
Ravulizumab SC Treatment GroupExperimentalIn 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.
Receives: Combination Product: Ravulizumab OBDS; Biological: Ravulizumab
Ravulizumab IV Treatment GroupActive comparatorIn 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.
Receives: Combination Product: Ravulizumab OBDS; Biological: Ravulizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ctrough Serum Concentration of Ravulizumab

    Measured: Predose at Day 71

Secondary outcomes (15)
  1. Ctrough Serum Concentration of Ravulizumab at Day 351

    Measured: Predose at Day 351

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

    Measured: Predose at Day 71

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

    Measured: Predose at Day 351

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

    Baseline was defined as the last assessment prior to first study drug dose. LDH samples impacted by tabletop hemolysis were excluded from the analysis.

    Measured: Baseline, Day 71

  5. Percent Change From Baseline in LDH Levels at Day 351

    SC baseline was defined as the last assessment prior to first dose of SC treatment. LDH samples impacted by tabletop hemolysis were excluded from the analysis.

    Measured: Baseline, Day 351

  6. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71

    FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Items are scored on a 5 point Likert-type scale. Item scores ranged from 0 ("not at all") to 4 ("very much"). The total, summed score ranged from 0 to 52; lower scores indicating greater fatigue and higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of study drug.

    Measured: Baseline, Day 71

  7. Change From Baseline in FACIT-Fatigue Scale Version 4 Score at Day 351

    FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Items are scored on a 5 point Likert-type scale. Item scores ranged from 0 ("not at all") to 4 ("very much"). The total, summed score ranged from 0 to 52; lower scores indicating greater fatigue and higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of subcutaneous treatment.

    Measured: Baseline, Day 351

  8. Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71

    The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.

    Measured: Baseline, Day 71

  9. Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351

    The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.

    Measured: Baseline, Day 351

  10. Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71

    Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 grams/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*upper limit of normal (ULN). Denominator for a percentage was participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess breakthrough hemolysis.

    Measured: Baseline up to Day 71

  11. Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351

    Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*ULN. Denominator for a percentage was participants with at least one post-baseline data for the period.

    Measured: Baseline up to Day 351

  12. Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71

    Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Percentages are based on participants with any post-baseline data for the period. For Through Day 71, only visits with data were used to assess transfusion avoidance.

    Measured: Baseline up to Day 71

  13. Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351

    Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period.

    Measured: Baseline up to Day 351

  14. Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) up to Day 71

    SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline (defined as the last assessment prior to the first dose of the study drug) in the absence of transfusion to the end of the period of interest. Percentages were based on participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess SHg.

    Measured: Baseline up to Day 71

  15. Percentage of Participants Who Maintained SHg up to Day 351

    SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from SC Baseline (defined as the last assessment prior to the first dose of SC treatment) in the absence of transfusion to the end of the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period. Visits were based on the number of days since first dose of SC treatment.

    Measured: Baseline up to Day 351

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2018
  2. Study start19 Feb 2019
  3. Primary completion2 Feb 2021
  4. Study completion31 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
139 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03748823
Sponsor's protocol ID
ALXN1210-PNH-303
Other IDs
2017-002370-39, 2017
Status last verified
Aug 2024
First submitted
19 Nov 2018
Last updated
19 Sep 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 36272026

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ravulizumab OBDS and Ravulizumab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Alexion Pharmaceuticals, Inc. at 51 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in France, Spain, Brazil, Turkey (Türkiye), Belgium and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ctrough Serum Concentration of Ravulizumab (time frame: Predose at Day 71). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03748823, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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