Paroxysmal Nocturnal Hemoglobinuria (PNH)Phase 3NCT03056040
ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
A Phase 3 study testing Ravulizumab and Eculizumab in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Alexion Pharmaceuticals, Inc. at 51 sites in 11 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- What is being tested?
- Ravulizumab and Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 202 participants
- Where
- 51 sitesin 11 countries
- Study dates
- 17 May 2017to 21 Feb 2022
- 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 6 months prior to Day 1.
- Lactate dehydrogenase level ≤1.5 times the upper limit of normal (ULN) at screening.
- PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
- Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
- 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
- History of bone marrow transplantation.
- Body weight <40 kilograms at screening.
- 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 bleeding, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, or coexisting chronic anemia unrelated to PNH).
- Female participants 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 treatment 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 11 countries.
51 sites in 11 countries
South Korea9 sites
Research Site
Bucheon-si, 14584
Research Site
Daegu, 42415
Research Site
Daejeon, 35015
Research Site
Incheon, 21565
Research Site
Seoul, 03080
Research Site
Seoul, 06351
Research Site
Seoul, 3722
Research Site
Seoul, 6591
Research Site
Suwon, 16247
France8 sites
Research Site
Amiens, 80054
Research Site
La Tronche, 38043
Research Site
Marseille, 13273
Research Site
Nice, 06200
Research Site
Paris, 75475
Research Site
Pierre-Bénite, 69495
Research Site
Saint-Priest-en-Jarez, 42270
Research Site
Strasbourg, 67091
United States5 sites
Research Site
Baltimore, Maryland, 21205
Research Site
Detroit, Michigan, 48202
Research Site
Duarte, California, 91010
Research Site
Los Angeles, California, 90089
Research Site
The Bronx, New York, 10467
Australia5 sites
Research Site
Canberra, 2605
Research Site
Kogarah, 2217
Research Site
Liverpool, 2170
Research Site
Melbourne, 3000
Research Site
Woolloongabba, 4102
Italy5 sites
Research Site
Florence, 50134
Research Site
Milan, 20122
Research Site
Naples, 80131
Research Site
Torino, 10126
Research Site
Vicenza, 36100
Japan5 sites
Research Site
Fukushima, 960-1295
Research Site
Kanazawa, 920-8641
Research Site
Shinagawa-ku, 141-0022
Research Site
Suita-shi, 565-0871
Research Site
Suwa-shi, 392-8510
Canada3 sites
Research Site
Montreal, Quebec, H1T 2M4
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Toronto, Ontario, M5G 2C4
Germany3 sites
Research Site
Aachen, 52074
Research Site
Essen, 45147
Research Site
Ulm, 89081
Spain3 sites
Research Site
Barcelona, 8036
Research Site
Madrid, 28040
Research Site
Majadahonda, 28220
United Kingdom3 sites
Research Site
Airdrie, ML6 0JS
Research Site
Leeds, LS9 7TF
Research Site
London, SE5 9NU
Netherlands2 sites
Research Site
Maastricht, 6202 AZ
Research Site
Nijmegen, 6525 GA
About this study
Official title: 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.
Read the 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.
- Being tested
- Ravulizumab, Eculizumab
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RavulizumabBiological
Also called ALXN1210, ULTOMIRIS
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.
EculizumabBiological
All treatments were given as IV infusions. Participants received 900 mg of eculizumab q2w.
| Study group | Role | What they receive |
|---|---|---|
| Ravulizumab | Experimental | 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. Receives: Biological: Ravulizumab |
| Eculizumab | Active comparator | 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. Receives: Biological: Ravulizumab; Biological: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change In Lactate Dehydrogenase Levels From Baseline To 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).
Measured: Baseline, Day 183
Secondary outcomes (8)
Number Of Participants With Breakthrough Hemolysis 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).
Measured: Baseline through Day 183
Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores
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.
Measured: Baseline, Day 183
Percentage Of Participants Who Achieved Transfusion Avoidance 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.
Measured: Baseline through Day 183
Percentage Of Participants With Stabilized Hemoglobin Levels 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.
Measured: Baseline through Day 183
Number Of Participants With Breakthrough Hemolysis Through End of Study
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.
Measured: Baseline through end of study (up to 4 years)
Change From Baseline To End of Study In FACIT-Fatigue Scores Through End of Study
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.
Measured: Baseline, End of Study (up to 4 years)
Percentage Of Participants Who Achieved Transfusion Avoidance Through End of Study
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.
Measured: Baseline through end of study (up to 4 years)
Percentage Of Participants With Stabilized Hemoglobin Levels Through End of Study
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.
Measured: Baseline through end of study (up to 4 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2017
- Study start17 May 2017
- Primary completion21 Feb 2022
- Study completion21 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Nocturnal Hemoglobinuria (PNH)Studies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03056040
- Sponsor's protocol ID
- ALXN1210-PNH-302
- Other IDs
- 2016-002026-36, 2016
- Status last verified
- Feb 2025
- First submitted
- 14 Feb 2017
- Last updated
- 12 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, Gaya A, Lee JW, Gutierrez EO, Piatek CI, Szer J, Risitano A, Nakao S, Bachman E, Shafner L, Damokosh AI, Ortiz S, Roth A, Peffault de Latour R. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019 Feb 7;133(6):540-549. doi: 10.1182/blood-2018-09-876805. Epub 2018 Dec 3.
PubMed 30510079Brodsky RA, Peffault de Latour R, Rottinghaus ST, Roth A, Risitano AM, Weitz IC, Hillmen P, Maciejewski JP, Szer J, Lee JW, Kulasekararaj AG, Volles L, Damokosh AI, Ortiz S, Shafner L, Liu P, Hill A, Schrezenmeier H. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Jan 1;106(1):230-237. doi: 10.3324/haematol.2019.236877.
PubMed 31949012Ishiyama K, Nakao S, Usuki K, Yonemura Y, Ikezoe T, Uchiyama M, Mori Y, Fukuda T, Okada M, Fujiwara SI, Noji H, Rottinghaus S, Aguzzi R, Yokosawa J, Nishimura JI, Kanakura Y, Okamoto S. Results from multinational phase 3 studies of ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria: subgroup analysis of Japanese patients. Int J Hematol. 2020 Oct;112(4):466-476. doi: 10.1007/s12185-020-02934-6. Epub 2020 Aug 31.
PubMed 32869125Kulasekararaj AG, Griffin M, Langemeijer S, Usuki K, Kulagin A, Ogawa M, Yu J, Mujeebuddin A, Nishimura JI, Lee JW, Peffault de Latour R; 301/302 Study Group. Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies. Eur J Haematol. 2022 Sep;109(3):205-214. doi: 10.1111/ejh.13783. Epub 2022 Jun 16.
PubMed 35502600Kulasekararaj AG, Hill A, Langemeijer S, Wells R, Gonzalez Fernandez FA, Gaya A, Ojeda Gutierrez E, Piatek CI, Mitchell L, Usuki K, Bosi A, Brodsky RA, Ogawa M, Yu J, Ortiz S, Roth A, Lee JW, Peffault de Latour R. One-year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab. Eur J Haematol. 2021 Mar;106(3):389-397. doi: 10.1111/ejh.13564. Epub 2021 Jan 3.
PubMed 33301613Peffault de Latour R, Brodsky RA, Ortiz S, Risitano AM, Jang JH, Hillmen P, Kulagin AD, Kulasekararaj AG, Rottinghaus ST, Aguzzi R, Gao X, Wells RA, Szer J. Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies. Br J Haematol. 2020 Nov;191(3):476-485. doi: 10.1111/bjh.16711. Epub 2020 May 24.
PubMed 32449174Schrezenmeier H, Kulasekararaj A, Mitchell L, Sicre de Fontbrune F, Devos T, Okamoto S, Wells R, Rottinghaus ST, Liu P, Ortiz S, Lee JW, Socie G. One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitor therapy: open-label extension of a randomized study. Ther Adv Hematol. 2020 Oct 24;11:2040620720966137. doi: 10.1177/2040620720966137. eCollection 2020.
PubMed 33178408Wietz IC, Kulagin A, Nakao S, Piatek CI, Szer J, Rottinghaus ST, Volles L, Damokosh AI, Aguzzi R, Larratt L, Risitano AM. A Phase 3 study of ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitors: results of a subgroup analysis with patients stratified by baseline hemolysis level, transfusion history, and demographics. Blood. 2018;132 (Supplement 1):627. doi: 10.1182/blood-2018-99-110623
Kulasekararaj A, Brodsky R, Schrezenmeier H, Griffin M, Roth A, Piatek C, Ogawa M, Yu J, Patel AS, Patel Y, Notaro R, Usuki K, Kulagin A, Gualandro S, Fureder W, Peffault de Latour R, Szer J, Lee JW. Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria. Ann Hematol. 2025 Jan;104(1):81-94. doi: 10.1007/s00277-025-06193-5. Epub 2025 Jan 22.
PubMed 39841198Schwartz CE, Stark RB, Borowiec K, Nolte S, Myren KJ. Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Orphanet J Rare Dis. 2021 Sep 15;16(1):389. doi: 10.1186/s13023-021-02016-8.
PubMed 34526067
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03056040
- Acronym / sponsor ID
- ALXN1210-PNH-302
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 202 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 May 2017 (actual)
- Primary completion
- 21 Feb 2022 (actual)
- Study completion
- 21 Feb 2022 (actual)
- First posted
- 16 Feb 2017 (actual)
- Results
- Posted 21 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ravulizumab | Experimental | Biological: RavulizumabOn 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. |
| Eculizumab | Active comparator | Biological: Ravulizumab, Biological: EculizumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female ≥18 years of age.
- Treated with eculizumab for PNH for at least 6 months prior to Day 1.
- Lactate dehydrogenase level ≤1.5 times the upper limit of normal (ULN) at screening.
- PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
- Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
Key exclusion criteria (6 listed)
- History of bone marrow transplantation.
- Body weight <40 kilograms at screening.
- 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 bleeding, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, or coexisting chronic anemia unrelated to PNH).
- Female participants who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RavulizumabAlso: ALXN1210, ULTOMIRISAll 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. | Biological | Eculizumab, Ravulizumab |
| EculizumabAll treatments were given as IV infusions. Participants received 900 mg of eculizumab q2w. | Biological | Eculizumab |
Primary outcome
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).
8 secondary outcomes
Number Of Participants With Breakthrough Hemolysis Through Day 183
Time frame: Baseline through Day 183
Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores
Time frame: Baseline, Day 183
Percentage Of Participants Who Achieved Transfusion Avoidance Through Day 183
Time frame: Baseline through Day 183
Percentage Of Participants With Stabilized Hemoglobin Levels Through Day 183
Time frame: 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)
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)
Percentage Of Participants Who Achieved Transfusion Avoidance Through End of Study
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30510079Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, Gaya A, Lee JW, Gutierrez EO, Piatek CI, Szer J, Risitano A, Nakao S, Bachman E, Shafner L, Damokosh AI, Ortiz S, Roth A, Peffault de Latour R. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019 Feb 7;133(6):540-549. doi: 10.1182/blood-2018-09-876805. Epub 2018 Dec 3.
- Background: PubMed 31949012Brodsky RA, Peffault de Latour R, Rottinghaus ST, Roth A, Risitano AM, Weitz IC, Hillmen P, Maciejewski JP, Szer J, Lee JW, Kulasekararaj AG, Volles L, Damokosh AI, Ortiz S, Shafner L, Liu P, Hill A, Schrezenmeier H. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Jan 1;106(1):230-237. doi: 10.3324/haematol.2019.236877.
- Background: PubMed 32869125Ishiyama K, Nakao S, Usuki K, Yonemura Y, Ikezoe T, Uchiyama M, Mori Y, Fukuda T, Okada M, Fujiwara SI, Noji H, Rottinghaus S, Aguzzi R, Yokosawa J, Nishimura JI, Kanakura Y, Okamoto S. Results from multinational phase 3 studies of ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria: subgroup analysis of Japanese patients. Int J Hematol. 2020 Oct;112(4):466-476. doi: 10.1007/s12185-020-02934-6. Epub 2020 Aug 31.
- Background: PubMed 35502600Kulasekararaj AG, Griffin M, Langemeijer S, Usuki K, Kulagin A, Ogawa M, Yu J, Mujeebuddin A, Nishimura JI, Lee JW, Peffault de Latour R; 301/302 Study Group. Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies. Eur J Haematol. 2022 Sep;109(3):205-214. doi: 10.1111/ejh.13783. Epub 2022 Jun 16.
- Background: PubMed 33301613Kulasekararaj AG, Hill A, Langemeijer S, Wells R, Gonzalez Fernandez FA, Gaya A, Ojeda Gutierrez E, Piatek CI, Mitchell L, Usuki K, Bosi A, Brodsky RA, Ogawa M, Yu J, Ortiz S, Roth A, Lee JW, Peffault de Latour R. One-year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab. Eur J Haematol. 2021 Mar;106(3):389-397. doi: 10.1111/ejh.13564. Epub 2021 Jan 3.
- Background: PubMed 32449174Peffault de Latour R, Brodsky RA, Ortiz S, Risitano AM, Jang JH, Hillmen P, Kulagin AD, Kulasekararaj AG, Rottinghaus ST, Aguzzi R, Gao X, Wells RA, Szer J. Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies. Br J Haematol. 2020 Nov;191(3):476-485. doi: 10.1111/bjh.16711. Epub 2020 May 24.
- Background: PubMed 33178408Schrezenmeier H, Kulasekararaj A, Mitchell L, Sicre de Fontbrune F, Devos T, Okamoto S, Wells R, Rottinghaus ST, Liu P, Ortiz S, Lee JW, Socie G. One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitor therapy: open-label extension of a randomized study. Ther Adv Hematol. 2020 Oct 24;11:2040620720966137. doi: 10.1177/2040620720966137. eCollection 2020.
- BackgroundWietz IC, Kulagin A, Nakao S, Piatek CI, Szer J, Rottinghaus ST, Volles L, Damokosh AI, Aguzzi R, Larratt L, Risitano AM. A Phase 3 study of ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitors: results of a subgroup analysis with patients stratified by baseline hemolysis level, transfusion history, and demographics. Blood. 2018;132 (Supplement 1):627. doi: 10.1182/blood-2018-99-110623
- Derived from this study: PubMed 39841198Kulasekararaj A, Brodsky R, Schrezenmeier H, Griffin M, Roth A, Piatek C, Ogawa M, Yu J, Patel AS, Patel Y, Notaro R, Usuki K, Kulagin A, Gualandro S, Fureder W, Peffault de Latour R, Szer J, Lee JW. Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria. Ann Hematol. 2025 Jan;104(1):81-94. doi: 10.1007/s00277-025-06193-5. Epub 2025 Jan 22.
- Derived from this study: PubMed 34526067Schwartz CE, Stark RB, Borowiec K, Nolte S, Myren KJ. Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Orphanet J Rare Dis. 2021 Sep 15;16(1):389. doi: 10.1186/s13023-021-02016-8.
- Related InfoLink provided by the sponsor.
Related trials for Paroxysmal Nocturnal Hemoglobinuria (PNH)
Enrolling by invitationObservational study
An Observational Post-Authorization Safety and Effectiveness Study of Ravulizumab in Adult Patients Aged 18 and Older Diagnosed With Paroxysmal Nocturnal Hemoglobinuria Using Multicenter Electronic Medical Records in South Korea
Hemoglobinuria, Paroxysmal
RecruitingPhase 2
Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells
Severe Aplastic Anemia, MDS (Myelodysplastic Syndrome)
RecruitingPhase 3
A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works
Paroxysmal Nocturnal Hemoglobinuria
Not yet recruitingPhase 3
A Study of Efficacy and Safety of FXS6837 in Anti-C5 Treated PNH Patients.
Paroxysmal Nocturnal Hemoglobinuria
RecruitingPhase 2
Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis
Severe Aplastic Anemia (SAA), Hypo-Plastic Myelodysplastic Syndrome (MDS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
51 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ravulizumab and Eculizumab in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Alexion Pharmaceuticals, Inc. at 51 sites in 11 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 7 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 12 Mar 2025. 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 South Korea, France, United States, Australia, Italy and 6 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 21 Mar 2019). 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?
Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183 (time frame: Baseline, Day 183). 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 NCT03056040, which also lists 10 linked publications.
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 12 Mar 2025.