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NCT03056040

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

Completed Phase 3 Results posted Last updated 12 March 2025
What this trial tests

Phase 3 trial testing Ravulizumab in Paroxysmal Nocturnal Hemoglobinuria (PNH) in 202 participants. Completed in 21 February 2022.

Timeline
17 May 2017
Primary endpoint
21 February 2022
21 February 2022

Quick facts

Lead sponsorAlexion Pharmaceuticals, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designparallel
Maskingnone
Primary purposetreatment
Enrollment202
Start date17 May 2017
Primary completion21 February 2022
Estimated completion21 February 2022
Sites51 locations across France, Italy, Japan, Netherlands, United Kingdom, Germany, South Korea, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Alexion Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Paroxysmal Nocturnal Hemoglobinuria (PNH). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183 Primary · 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 strati

GroupValue95% CI
Ravulizumab/Ravulizumab-0.82-7.75 – 6.11
Eculizumab/Ravulizumab8.391.47 – 15.32
Number Of Participants With Breakthrough Hemolysis Through Day 183 Secondary · 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).

GroupValue95% CI
Ravulizumab/Ravulizumab00.00 – 3.73
Eculizumab/Ravulizumab51.68 – 11.51
Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores Secondary · 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.

GroupValue95% CI
Ravulizumab/Ravulizumab2.010.64 – 3.39
Eculizumab/Ravulizumab0.54-0.84 – 1.93
Percentage Of Participants Who Achieved Transfusion Avoidance Through Day 183 Secondary · 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.

GroupValue95% CI
Ravulizumab/Ravulizumab87.681.08 – 94.18
Eculizumab/Ravulizumab82.775.16 – 90.15
Percentage Of Participants With Stabilized Hemoglobin Levels Through Day 183 Secondary · 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.

GroupValue95% CI
Ravulizumab/Ravulizumab76.367.82 – 84.75
Eculizumab/Ravulizumab75.567.00 – 84.02
Number Of Participants With Breakthrough Hemolysis Through End of Study Secondary · 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.

GroupValue95% CI
Ravulizumab/Ravulizumab94.38 – 17.05
Eculizumab/Ravulizumab62.35 – 13.24
Change From Baseline To End of Study In FACIT-Fatigue Scores Through End of Study Secondary · 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.

GroupValue95% CI
Ravulizumab/Ravulizumab-1.43± 5.694
Eculizumab/Ravulizumab0.00± 5.944
Percentage Of Participants Who Achieved Transfusion Avoidance Through End of Study Secondary · 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.

GroupValue95% CI
Ravulizumab/Ravulizumab70.8360.67 – 79.67
Eculizumab/Ravulizumab70.5360.29 – 79.44
Percentage Of Participants With Stabilized Hemoglobin Levels Through End of Study Secondary · 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.

GroupValue95% CI
Ravulizumab/Ravulizumab58.3347.82 – 68.32
Eculizumab/Ravulizumab67.3759.68 – 76.64

Adverse events — posted to ClinicalTrials.gov

Time frame: From Baseline (after first dose) to end of study (up to 4 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Primary Evaluation Period (26 Weeks) Ravulizumab Treatment
Serious: 4/97 (4%)
Deaths: 0/97
Primary Evaluation Period (26 Weeks) Eculizumab Treatment
Serious: 8/98 (8%)
Deaths: 0/98
Extension Period (Ravulizumab To Ravulizumab)
Serious: 26/96 (27%)
Deaths: 0/96
Extension Period (Eculizumab to Ravulizumab)
Serious: 33/95 (35%)
Deaths: 3/95

Serious adverse events (65 terms)

ReactionSystemPrimary Evaluation Period …Primary Evaluation Period …Extension Period (Ravulizu…Extension Period (Eculizum…
PyrexiaGeneral disorders
HaemolysisBlood and lymphatic system disorders
InfluenzaInfections and infestations
Haemolytic anaemiaBlood and lymphatic system disorders
InfectionInfections and infestations
PalpitationsCardiac disorders
ColitisGastrointestinal disorders
HyperthermiaGeneral disorders
CholelithiasisHepatobiliary disorders
Lower respiratory tract infectionInfections and infestations
Pyelonephritis acuteInfections and infestations
EpilepsyNervous system disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Aplastic anaemiaBlood and lymphatic system disorders
Bone marrow failureBlood and lymphatic system disorders
Breakthrough haemolysisBlood and lymphatic system disorders
EnteritisGastrointestinal disorders
PneumoperitoneumGastrointestinal disorders
ToothacheGastrointestinal disorders
Bile duct stoneHepatobiliary disorders
Biliary colicHepatobiliary disorders
CholecystitisHepatobiliary disorders
Liver disorderHepatobiliary disorders
COVID-19Infections and infestations
Other adverse events (45 terms — click to expand)

ReactionSystemPrimary Evaluation Period …Primary Evaluation Period …Extension Period (Ravulizu…Extension Period (Eculizum…
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Upper respiratory tract infectionInfections and infestations
FatigueGeneral disorders
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
DizzinessNervous system disorders
Back painMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
RhinitisInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Chest painGeneral disorders
Influenza like illnessGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
Urinary tract infectionInfections and infestations
AnaemiaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
GastroenteritisInfections and infestations
ConstipationGastrointestinal disorders
DysphagiaGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
ContusionInjury, poisoning and procedural complications
Viral infectionInfections and infestations
Musculoskeletal painMusculoskeletal and connective tissue disorders
InfluenzaInfections and infestations
PalpitationsCardiac disorders
PruritusSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
Ear painEar and labyrinth disorders
Abdominal discomfortGastrointestinal disorders
Oedema peripheralGeneral disorders
AstheniaGeneral disorders
CholelithiasisHepatobiliary disorders
COVID-19Infections and infestations
Respiratory tract infectionInfections and infestations

Most-reported serious reactions: Pyrexia, Haemolysis, Influenza, Haemolytic anaemia, Infection, Palpitations, Colitis, Hyperthermia.

Data from ClinicalTrials.gov NCT03056040 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. New insights into the immune functions of complement.
    Reis ES, Mastellos DC, Hajishengallis G, Lambris JD. · · 2019 · cited 357× · PMID 31048789 · DOI 10.1038/s41577-019-0168-x
  2. The renaissance of complement therapeutics.
    Ricklin D, Mastellos DC, Reis ES, Lambris JD. · · 2018 · cited 305× · PMID 29199277 · DOI 10.1038/nrneph.2017.156
  3. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study.
    Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, et al · · 2019 · cited 277× · PMID 30510079 · DOI 10.1182/blood-2018-09-876805
  4. Antibodies to watch in 2018.
    Kaplon H, Reichert JM. · · 2018 · cited 179× · PMID 29300693 · DOI 10.1080/19420862.2018.1415671
  5. Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT.
    Risitano AM, Marotta S, Ricci P, Marano L, et al · · 2019 · cited 155× · PMID 31258525 · DOI 10.3389/fimmu.2019.01157
  6. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria.
    Brodsky RA, Peffault de Latour R, Rottinghaus ST, Röth A, et al · · 2021 · cited 96× · PMID 31949012 · DOI 10.3324/haematol.2019.236877
  7. Diseases of complement dysregulation-an overview.
    Wong EKS, Kavanagh D. · · 2018 · cited 80× · PMID 29327071 · DOI 10.1007/s00281-017-0663-8
  8. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies.
    Röth A, Rottinghaus ST, Hill A, Bachman ES, et al · · 2018 · cited 65× · PMID 30171081 · DOI 10.1182/bloodadvances.2018020644

Verify or expand the search:

Other trials of Ravulizumab

Trials testing the same drug.

Other recruiting trials for Paroxysmal Nocturnal Hemoglobinuria (PNH)

Currently open trials in the same condition.

Other Alexion Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing