ALXN1210 (Ravulizumab) Versus Eculizumab in Complement Inhibitor Treatment-Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

April 18, 2024 updated by: Alexion Pharmaceuticals, Inc.

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

The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who had never been treated with a complement inhibitor (treatment-naïve).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 26-week Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive ravulizumab for up to 5 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
272

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Argentina
      • Buenos Aires, Argentina, C1015ABO
        • Research Site
      • Buenos Aires, Argentina, C1425AUM
        • Research Site
      • Córdoba, Argentina, X5004BAL
        • Research Site
  • Australia
      • Perth, Australia, 6000
        • Research Site
  • Austria
      • Linz, Austria, 4020
        • Research Site
      • Vienna, Austria, A-1090
        • Research Site
  • Belgium
      • Bruxelles, Belgium, 1200
        • Research Site
      • Hasselt, Belgium, 3500
        • Research Site
      • Leuven, Belgium, 3000
        • Research Site
  • Brazil
      • Rio De Janeiro, Brazil
        • Research Site
      • Salvador, Brazil, 41253-190
        • Research Site
      • Sao Paulo, Brazil
        • Research Site
      • Sao Paulo, Brazil, 05403-000
        • Research Site
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2G3
        • Research Site
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Research Site
  • Czechia
      • Plzeň, Czechia, 323 00
        • Research Site
      • Prague, Czechia
        • Research Site
  • Estonia
      • Tallinn, Estonia, 13419
        • Research Site
  • France
      • Limoges, France, 87042
        • Research Site
      • MONTPELLIER Cedex 5, France, 34295
        • Research Site
      • Paris Cedex 10, France, 75475
        • Research Site
      • Pierre Benite, France, 69310
        • Research Site
      • Poitiers, France, 86021
        • Research Site
      • Rennes Cedex 9, France, 35033
        • Research Site
  • Germany
      • Aachen, Germany, 52074
        • Research Site
      • Essen, Germany, 45122
        • Research Site
      • Ulm, Germany, 89081
        • Research Site
  • Italy
      • Ascoli Piceno, Italy, 63100
        • Research Site
      • Firenze, Italy, 50134
        • Research Site
      • Milano, Italy, 20122
        • Research Site
      • Napoli, Italy, 80131
        • Research Site
      • Vicenza, Italy, 36100
        • Research Site
  • Japan
      • Bunkyo-ku, Japan, 113-8431
        • Research Site
      • Bunkyo-ku, Japan, 113-8519
        • Research Site
      • Fukuoka-Shi, Japan, 812-8582
        • Research Site
      • Fukushima-shi, Japan, 960-1295
        • Research Site
      • Hamamatsu-shi, Japan, 432-8580
        • Research Site
      • Kanazawa-shi, Japan, 920-8641
        • Research Site
      • Kitakyusyu-shi, Japan, 806-8501
        • Research Site
      • Koshigaya-shi, Japan, 343-8555
        • Research Site
      • Kumamoto-shi, Japan, 860-8556
        • Research Site
      • Nagoya-shi, Japan, 453-8511
        • Research Site
      • Nishinomiya-shi, Japan, 663-8501
        • Research Site
      • Ogaki-shi, Japan, 503-8502
        • Research Site
      • Okayama-shi, Japan, 700-8558
        • Research Site
      • Okayama-shi, Japan, 701-1192
        • Research Site
      • Osakasayama-shi, Japan, 589-8511
        • Research Site
      • Sapporo-shi, Japan, 060-8543
        • Research Site
      • Shimotsuke-shi, Japan, 329-0498
        • Research Site
      • Shinjuku-ku, Japan, 160-8582
        • Research Site
      • Shinjuku-ku, Japan, 160-0023
        • Research Site
      • Suita, Japan, 565-0871
        • Research Site
      • Tokorozawa-shi, Japan
        • Research Site
      • Tokyo, Japan
        • Research Site
      • Toyoake-shi, Japan, 470-1192
        • Research Site
      • Tsukuba-shi, Japan, 305-8576
        • Research Site
      • Wakayama-shi, Japan, 641-8510
        • Research Site
  • Korea, Republic of
      • Daejeon, Korea, Republic of, 35015
        • Research Site
      • Goyang-si, Korea, Republic of, 10408
        • Research Site
      • Incheon, Korea, Republic of, 21565
        • Research Site
      • Jeonju-si, Korea, Republic of, 561-712
        • Research Site
      • JinJoo, Korea, Republic of, 52727
        • Research Site
      • Jung-gu, Korea, Republic of, 41944
        • Research Site
      • Seoul, Korea, Republic of, 03722
        • Research Site
      • Seoul, Korea, Republic of, 03080
        • Research Site
      • Seoul, Korea, Republic of, 135-710
        • Research Site
      • Seoul, Korea, Republic of, 02841
        • Research Site
      • Seoul, Korea, Republic of, 06591
        • Research Site
      • Seoul, Korea, Republic of, 07985
        • Research Site
      • Seoul, Korea, Republic of, 04401
        • Research Site
      • Seoul, Korea, Republic of, 152703
        • Research Site
      • Songpa-gu, Korea, Republic of, 05505
        • Research Site
      • Suwon-si, Korea, Republic of, 16247
        • Research Site
      • Ulsan, Korea, Republic of, 44033
        • Research Site
  • Malaysia
      • George, Malaysia, 10990
        • Research Site
      • Johor Bahru, Malaysia, 80100
        • Research Site
      • Kota Bharu, Malaysia, 15586
        • Research Site
      • Kota Bharu, Malaysia, 16150
        • Research Site
      • Kota Kinabalu, Malaysia, 88586
        • Research Site
      • Kuching, Malaysia, 93586
        • Research Site
      • Miri, Malaysia, 98000
        • Research Site
      • Sibu, Malaysia, 96000
        • Research Site
  • Mexico
      • Monterrey, Mexico, 64460
        • Research Site
  • Poland
      • Gdańsk, Poland, 80-214
        • Research Site
      • Warszawa, Poland, 02-172
        • Research Site
  • Russian Federation
      • Arkhangelsk, Russian Federation, 163045
        • Research Site
      • Barnaul, Russian Federation, 656024
        • Research Site
      • Irkutsk, Russian Federation, 664079
        • Research Site
      • Kirov, Russian Federation, 610027
        • Research Site
      • Moscow, Russian Federation, 117997
        • Research Site
      • Moscow, Russian Federation, 125284
        • Research Site
      • Murmansk, Russian Federation, 183047
        • Research Site
      • Novosibirsk, Russian Federation, 630091
        • Research Site
      • Omsk, Russian Federation, 644013
        • Research Site
      • Petrozavodsk, Russian Federation, 185019
        • Research Site
      • Rostov-on-Don, Russian Federation, 344022
        • Research Site
      • Saint-Petersburg, Russian Federation, 197022
        • Research Site
      • Saratov, Russian Federation, 410028
        • Research Site
      • St. Petersburg, Russian Federation
        • Research Site
      • Ufa, Russian Federation, 450005
        • Research Site
  • Serbia
      • Belgrade, Serbia, 11000
        • Research Site
  • Singapore
      • Singapore, Singapore, 119228
        • Research Site
  • Spain
      • Madrid, Spain, 28040
        • Research Site
      • Majadahonda, Spain, 28220
        • Research Site
  • Sweden
      • Uppsala, Sweden, 75185
        • Research Site
  • Taiwan
      • Changhua, Taiwan, 50006
        • Research Site
      • Hualien City, Taiwan, 97002
        • Research Site
      • Taichung, Taiwan, 404
        • Research Site
      • Tainan, Taiwan, 70403
        • Research Site
      • Taipei, Taiwan, 100
        • Research Site
  • Thailand
      • Bangkok, Thailand, 10330
        • Research Site
      • Bangkok, Thailand, 10700
        • Research Site
      • Songkhla, Thailand, 90110
        • Research Site
  • Turkey
      • Eskisehir, Turkey, 26040
        • Research Site
  • United Kingdom
      • Airdrie, United Kingdom, ML6 0JS
        • Research Site
      • Leeds, United Kingdom
        • Research Site
      • London, United Kingdom, SE5 9NU
        • Research Site
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • Research Site
      • Whittier, California, United States, 90603
        • Research Site
    • Texas
      • Fort Worth, Texas, United States, 76104
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Criteria For Patient Cohort Originally Enrolled in ALXN1210-PNH-301 Study: Inclusion Criteria: 1. Male or female ≥18 years of age. 2. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry. 3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin <10 gram/deciliter), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cells (pRBC) transfusion due to PNH. 4. Lactate dehydrogenase (LDH) level ≥1.5 times the upper limit of normal at screening. 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. Treatment with a complement inhibitor at any time. 2. History of bone marrow transplantation. 3. Body weight <40 kg. 4. Females who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1. 5. 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. 6. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation. 7. 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). Eligibility Criteria For Roll-over Cohort: 1. All participants regardless of age, who are currently receiving ALXN1210 IV in an ongoing ALXN1210 study in patients with PNH 2. Participants must be willing and able to give written informed consent and to comply with all Extension study visits and procedures, including the use of any data collection device(s) to directly record patient data 3. Females of childbearing potential and male patients with female partners of childbearing potential must use highly effective contraception continuing until at least 8 months after the last dose of ravulizumab.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ravulizumab
Biological: Ravulizumab
All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to <60 kilogram (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
Biological: Ravulizumab
All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to <60 kilogram (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 were administered induction doses of 600 mg followed by maintenance doses of 900 mg.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage Of Participants Who Achieved Transfusion Avoidance (TA)
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 through Day 183.
Baseline through Day 183
Proportion Of Participants With Normalization Of Lactate Dehydrogenase (LDH) Levels
Time Frame: Day 29 through Day 183
LDH is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria (PNH). A decrease in LDH from above the upper limit of normal (ULN) to below the ULN indicates reduction (improvement) in hemolysis. Normalization of LDH levels (LDH-N) was LDH levels less than or equal to 1 x ULN, from Day 29 through Day 183. The ULN for LDH is 246 U/L.
Day 29 through Day 183

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage Of Participants With Breakthrough Hemolysis (BTH)
Time Frame: Baseline through Day 183
Breakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 gram/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 × ULN, after prior LDH reduction to <1.5 × ULN on therapy.
Baseline through Day 183
Change From Baseline In Quality Of Life As Assessed By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue
Time Frame: Baseline, Day 183
FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue. Baseline is defined as the last non-missing value prior to first dose of study drug. Estimates are based on MMRM that includes treatment group, the observed stratification randomization indicators (history of transfusion and LDH) and baseline FACIT-Fatigue level, study visit, and study visit by treatment group interaction. An unstructured covariance structure was used.
Baseline, Day 183
Percentage Of Participants With Stabilized Hemoglobin Levels
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
Percent Change From Baseline In LDH Levels
Time Frame: Baseline, Day 183
Baseline is defined as the average of all available assessments of LDH levels prior to first study drug dose. Estimates are based on Mixed Model for Repeated Measures (MMRM) that includes treatment group, history of transfusion (as a categorical variable based on the stratification factor levels) and baseline LDH level (as a continuous variable), study visit and study visit by treatment group interaction. An unstructured covariance structure was used.
Baseline, Day 183

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 12, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 25, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 27, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 14, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ALXN1210-PNH-301
  • 2016-002025-11

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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