ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab

February 24, 2025 updated by: Alexion Pharmaceuticals, Inc.

A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab

The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who were clinically stable after having been treated with eculizumab for at least 6 months.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study consisted of a 4-week Screening Period and a 26-week Randomized Treatment Period (Primary Evaluation Period). After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive ravulizumab for up to 4 years.

Study Type

Interventional

Enrollment (Actual)

202

Phase

  • Phase 3

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

  • Australia
      • Canberra, Australia, 2605
        • Research Site
      • Kogarah, Australia, 2217
        • Research Site
      • Liverpool, Australia, 2170
        • Research Site
      • Melbourne, Australia, 3000
        • Research Site
      • Woolloongabba, Australia, 4102
        • Research Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Research Site
      • Toronto, Ontario, Canada, M5G 2C4
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Research Site
  • France
      • Amiens, France, 80054
        • Research Site
      • La Tronche, France, 38043
        • Research Site
      • Marseille, France, 13273
        • Research Site
      • Nice, France, 06200
        • Research Site
      • Paris, France, 75475
        • Research Site
      • Pierre-Benite, France, 69495
        • Research Site
      • Saint-Priest-En-Jarez, France, 42270
        • Research Site
      • Strasbourg, France, 67091
        • Research Site
  • Germany
      • Aachen, Germany, 52074
        • Research Site
      • Essen, Germany, 45147
        • Research Site
      • Ulm, Germany, 89081
        • Research Site
  • Italy
      • Firenze, Italy, 50134
        • Research Site
      • Milano, Italy, 20122
        • Research Site
      • Napoli, Italy, 80131
        • Research Site
      • Torino, Italy, 10126
        • Research Site
      • Vicenza, Italy, 36100
        • Research Site
  • Japan
      • Fukushima-shi, Japan, 960-1295
        • Research Site
      • Kanazawa-shi, Japan, 920-8641
        • Research Site
      • Shinagawa-ku, Japan, 141-0022
        • Research Site
      • Suita-shi, Japan, 565-0871
        • Research Site
      • Suwa-shi, Japan, 392-8510
        • Research Site
  • Korea, Republic of
      • Bucheon-si, Korea, Republic of, 14584
        • Research Site
      • Daegu, Korea, Republic of, 42415
        • Research Site
      • Daejeon, Korea, Republic of, 35015
        • Research Site
      • Incheon, Korea, Republic of, 21565
        • Research Site
      • Seoul, Korea, Republic of, 03080
        • Research Site
      • Seoul, Korea, Republic of, 06351
        • Research Site
      • Seoul, Korea, Republic of, 6591
        • Research Site
      • Seoul, Korea, Republic of, 3722
        • Research Site
      • Suwon, Korea, Republic of, 16247
        • Research Site
  • Netherlands
      • Maastricht, Netherlands, 6202 AZ
        • Research Site
      • Nijmegen, Netherlands, 6525 GA
        • Research Site
  • Spain
      • Barcelona, Spain, 8036
        • Research Site
      • Madrid, Spain, 28040
        • Research Site
      • Majadahonda, Spain, 28220
        • Research Site
  • United Kingdom
      • Airdrie, United Kingdom, ML6 0JS
        • Research Site
      • Leeds, United Kingdom, LS9 7TF
        • Research Site
      • London, United Kingdom, SE5 9NU
        • Research Site
  • United States
    • California
      • Duarte, California, United States, 91010
        • Research Site
      • Los Angeles, California, United States, 90089
        • Research Site
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Research Site
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Research Site
    • New York
      • Bronx, New York, United States, 10467
        • Research 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

Description

Inclusion Criteria:

  1. Male or female ≥18 years of age.
  2. Treated with eculizumab for PNH for at least 6 months prior to Day 1.
  3. Lactate dehydrogenase level ≤1.5 times the upper limit of normal (ULN) at screening.
  4. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
  5. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
  6. 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.
  7. Willing and able to give written informed consent and comply with study visit schedule.

Exclusion Criteria:

  1. History of bone marrow transplantation.
  2. Body weight <40 kilograms at screening.
  3. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.
  4. Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleeding, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, or coexisting chronic anemia unrelated to PNH).
  5. Female participants who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1.
  6. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study treatment on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ravulizumab

On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 milligrams (mg). Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127.

After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 4 years.
Biological: Ravulizumab
All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to <60 kilograms (kg): 2400 mg was given as a single loading dose, followed by 3000 mg as maintenance dose. For participants weighing ≥60 to <100 kg: 2700 mg was given as a loading dose, followed by 3300 mg as maintenance dose. For participants weighing ≥100 kg: 3000 mg was given as a loading dose, followed by 3600 mg as maintenance dose.
Other Names:
  • ALXN1210
  • ULTOMIRIS
Active Comparator: Eculizumab

Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks.

After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 4 years.
Biological: Ravulizumab
All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to <60 kilograms (kg): 2400 mg was given as a single loading dose, followed by 3000 mg as maintenance dose. For participants weighing ≥60 to <100 kg: 2700 mg was given as a loading dose, followed by 3300 mg as maintenance dose. For participants weighing ≥100 kg: 3000 mg was given as a loading dose, followed by 3600 mg as maintenance dose.
Other Names:
  • ALXN1210
  • ULTOMIRIS
Biological: Eculizumab
All treatments were given as IV infusions. Participants received 900 mg of eculizumab q2w.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183
Time Frame: Baseline, Day 183
Lactate dehydrogenase (LDH) is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria. A decrease in LDH indicates reduction (improvement) in hemolysis. Baseline was defined as the average of all available on-study assessments prior to the first study drug infusion. The percent change in LDH was analyzed using a mixed-effect model for repeated measures (MMRM) with the fixed, categorical effects of treatment, study visit, and study visit by treatment group interaction, as well as the continuous, fixed covariate of baseline LDH and the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1).
Baseline, Day 183

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores
Time Frame: Baseline, Day 183
FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue. Baseline was defined as the last non-missing assessment value prior to first study drug dose. Change in FACIT-Fatigue score from Baseline to Day 183 was analyzed using an MMRM with the fixed, categorical effects of treatment, the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1), study visit, and study visit by treatment group interaction, as well as the continuous fixed covariate of Baseline FACIT-Fatigue score.
Baseline, Day 183
Number Of Participants With Breakthrough Hemolysis Through Day 183
Time Frame: Baseline through Day 183
Breakthrough hemolysis (BTH) was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin <10 grams (g)/deciliter (dL)], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 times the upper limit of normal (ULN).
Baseline through Day 183
Percentage Of Participants Who Achieved Transfusion Avoidance Through Day 183
Time Frame: Baseline through Day 183
Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines (hemoglobin value of ≤9 g/dL with signs or symptoms of sufficient severity to warrant a transfusion, or a hemoglobin value of ≤7 g/dL regardless of presence of clinical signs or symptoms) through Day 183.
Baseline through Day 183
Percentage Of Participants With Stabilized Hemoglobin Levels Through Day 183
Time Frame: Baseline through Day 183
Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline in the absence of transfusion through Day 183.
Baseline through Day 183
Number Of Participants With Breakthrough Hemolysis Through End of Study
Time Frame: Baseline through end of study (up to 4 years)
BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin <10 g/dL], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 times the ULN.
Baseline through end of study (up to 4 years)
Change From Baseline To End of Study In FACIT-Fatigue Scores Through End of Study
Time Frame: Baseline, End of Study (up to 4 years)
FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue. Baseline was defined as the last non-missing assessment value prior to first study drug dose. Change in FACIT-Fatigue score from Baseline to Day 183 was analyzed using an MMRM with the fixed, categorical effects of treatment, the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1), study visit, and study visit by treatment group interaction, as well as the continuous fixed covariate of Baseline FACIT-Fatigue score.
Baseline, End of Study (up to 4 years)
Percentage Of Participants Who Achieved Transfusion Avoidance Through End of Study
Time Frame: Baseline through end of study (up to 4 years)
Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines (hemoglobin value of ≤9 g/dL with signs or symptoms of sufficient severity to warrant a transfusion, or a hemoglobin value of ≤7 g/dL regardless of presence of clinical signs or symptoms) through the end of study.
Baseline through end of study (up to 4 years)
Percentage Of Participants With Stabilized Hemoglobin Levels Through End of Study
Time Frame: Baseline through end of study (up to 4 years)
Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline in the absence of transfusion through end of study.
Baseline through end of study (up to 4 years)

Collaborators and Investigators

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

Sponsor

Alexion Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

May 17, 2017

Primary Completion (Actual)

February 21, 2022

Study Completion (Actual)

February 21, 2022

Study Registration Dates

First Submitted

February 14, 2017

First Submitted That Met QC Criteria

February 14, 2017

First Posted (Actual)

February 16, 2017

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 24, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALXN1210-PNH-302
  • 2016-002026-36 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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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