Clinical Trial Results:
Phase 4, Single-Arm Study of Ravulizumab in Adult Participants with Paroxysmal Nocturnal Hemoglobinuria Currently Treated with High-Dose Eculizumab
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Summary
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EudraCT number |
2019-003440-74 |
Trial protocol |
GB |
Global end of trial date |
20 Dec 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Dec 2023
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First version publication date |
17 Dec 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ALXN1210-PNH-401
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04320602 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Alexion Pharmaceuticals Inc.
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Sponsor organisation address |
100 College Street, New Haven, CT, United States, 06510
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Public contact |
Alexion Europe SAS European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 7 87148158, clinicaltrials.eu@alexion.com
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Scientific contact |
Alexion Europe SAS European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 7 87148158, clinicaltrials.eu@alexion.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Dec 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Dec 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Dec 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to evaluate the prevalence of free complement component 5 (C5)-associated breakthrough hemolysis (BTH) in participants on high-dose eculizumab who switched to ravulizumab (per approved dose regimen).
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Protection of trial subjects |
This study was conducted in accordance with the protocol and with the consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, applicable International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and applicable laws and regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Mar 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 18
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Worldwide total number of subjects |
18
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
15
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||
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Pre-assignment
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Screening details |
The study consisted of a Screening Period of approximately 3 months and a Treatment Period of 351 days. Eligible participants were administered eculizumab 1200 milligrams (mg) every 2 weeks (q2w) optionally at home at the discretion of the Investigator, and preference of the participant during the Screening Period. | ||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||
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Arms
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Arm title
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Ravulizumab | ||||||||
Arm description |
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and every 8 weeks (q8w) thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen. | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
Ravulizumab
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Investigational medicinal product code |
ALXN1210
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Other name |
Ultomiris
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Pharmaceutical forms |
Sterile concentrate
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ravulizumab was administered per schedule specified in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
Ravulizumab
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Reporting group description |
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and every 8 weeks (q8w) thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ravulizumab
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Reporting group description |
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and every 8 weeks (q8w) thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen. | ||
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End point title |
Percentage of Participants Who Experienced Free C5-associated BTH [1] | ||||||||
End point description |
Free C5-associated BTH was defined as BTH concurrent with free C5 concentrations ≥0.5 micrograms (μg)/milliliter (mL). BTH 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 {g}/deciliter {dL}], major adverse vascular event [MAVE], including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated lactate dehydrogenase (LDH) ≥2 * upper limit of normal (ULN). The full analysis set (FAS) included all participants who received at least 1 dose of ravulizumab.
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End point type |
Primary
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End point timeframe |
Baseline through Day 351
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analysis was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent Change From Baseline in LDH at Day 351 | ||||||||
End point description |
The FAS included all participants who received at least 1 dose of ravulizumab. Here, 'Overall number of participants analyzed' = participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 351
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Who Experienced BTH | ||||||||
End point description |
BTH 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], MAVE, including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 * ULN. The FAS included all participants who received at least 1 dose of ravulizumab.
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End point type |
Secondary
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End point timeframe |
Baseline through Day 351
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End point title |
Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion | ||||||||
End point description |
The FAS included all participants who received at least 1 dose of ravulizumab.
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End point type |
Secondary
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End point timeframe |
Baseline through Day 351
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Stabilized Hemoglobin | ||||||||
End point description |
Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion from Baseline to Day 351.
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End point type |
Secondary
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End point timeframe |
Baseline through Day 351
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline through Day 351
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Adverse event reporting additional description |
Safety set included all participants who receive at least 1 dose of ravulizumab.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Ravulizumab
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Reporting group description |
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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29 Jan 2020 |
The main rationale for this amendment was to allow administration of eculizumab at the participant’s home at the discretion of the Investigator during Screening to reduce the burden of clinical visits. In addition, 2 specific patient-reported outcomes (Patient-Reported Symptoms [PRS] and Healthcare Resource Utilization [HRU]) are being included for exploratory data analysis. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
