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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002026-36 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ravulizumab | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Baseline, Day 183 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Duarte | California | 91010 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30510079 | Background | 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. | |
| 31949012 |
| Label | URL |
|---|---|
| Related Info | View source |
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Participants were stratified into 1 of 2 groups based on their transfusion history. Stratified participants were randomly assigned in a 1:1 ratio to receive ravulizumab or eculizumab.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ravulizumab/Ravulizumab | On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 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 received weight-based doses of ravulizumab for up to 4 years. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Primary Evaluation Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 1, 2019 | May 1, 2019 |
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|
|
| Eculizumab | Biological | All treatments were given as IV infusions. Participants received 900 mg of eculizumab q2w. |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline through end of study (up to 4 years) |
| Los Angeles |
| California |
| 90089 |
| United States |
| Research Site | Baltimore | Maryland | 21205 | United States |
| Research Site | Detroit | Michigan | 48202 | United States |
| Research Site | The Bronx | New York | 10467 | United States |
| Research Site | Canberra | 2605 | Australia |
| Research Site | Kogarah | 2217 | Australia |
| Research Site | Liverpool | 2170 | Australia |
| Research Site | Melbourne | 3000 | Australia |
| Research Site | Woolloongabba | 4102 | Australia |
| Research Site | Toronto | Ontario | M4N 3M5 | Canada |
| Research Site | Toronto | Ontario | M5G 2C4 | Canada |
| Research Site | Montreal | Quebec | H1T 2M4 | Canada |
| Research Site | Amiens | 80054 | France |
| Research Site | La Tronche | 38043 | France |
| Research Site | Marseille | 13273 | France |
| Research Site | Nice | 06200 | France |
| Research Site | Paris | 75475 | France |
| Research Site | Pierre-Bénite | 69495 | France |
| Research Site | Saint-Priest-en-Jarez | 42270 | France |
| Research Site | Strasbourg | 67091 | France |
| Research Site | Aachen | 52074 | Germany |
| Research Site | Essen | 45147 | Germany |
| Research Site | Ulm | 89081 | Germany |
| Research Site | Florence | 50134 | Italy |
| Research Site | Milan | 20122 | Italy |
| Research Site | Naples | 80131 | Italy |
| Research Site | Torino | 10126 | Italy |
| Research Site | Vicenza | 36100 | Italy |
| Research Site | Fukushima | 960-1295 | Japan |
| Research Site | Kanazawa | 920-8641 | Japan |
| Research Site | Shinagawa-ku | 141-0022 | Japan |
| Research Site | Suita-shi | 565-0871 | Japan |
| Research Site | Suwa-shi | 392-8510 | Japan |
| Research Site | Maastricht | 6202 AZ | Netherlands |
| Research Site | Nijmegen | 6525 GA | Netherlands |
| Research Site | Bucheon-si | 14584 | South Korea |
| Research Site | Daegu | 42415 | South Korea |
| Research Site | Daejeon | 35015 | South Korea |
| Research Site | Incheon | 21565 | South Korea |
| Research Site | Seoul | 03080 | South Korea |
| Research Site | Seoul | 06351 | South Korea |
| Research Site | Seoul | 3722 | South Korea |
| Research Site | Seoul | 6591 | South Korea |
| Research Site | Suwon | 16247 | South Korea |
| Research Site | Barcelona | 8036 | Spain |
| Research Site | Madrid | 28040 | Spain |
| Research Site | Majadahonda | 28220 | Spain |
| Research Site | Airdrie | ML6 0JS | United Kingdom |
| Research Site | Leeds | LS9 7TF | United Kingdom |
| Research Site | London | SE5 9NU | United Kingdom |
| Background |
| Brodsky 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. |
| 32869125 | Background | Ishiyama 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. |
| 35502600 | Background | Kulasekararaj 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. |
| 33301613 | Background | Kulasekararaj 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. |
| 32449174 | Background | Peffault 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. |
| 33178408 | Background | Schrezenmeier 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. |
| Background | Wietz 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 |
| 39841198 | Derived | 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. |
| 34526067 | Derived | Schwartz 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. |
| FG001 | Eculizumab/Ravulizumab | 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 received weight-based doses of ravulizumab for up to 4 years. |
| Received at Least 1 Dose of Study Drug | Participants included in the Safety Set |
|
| Participants in the Full Analysis Set (FAS) |
|
| COMPLETED |
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| NOT COMPLETED |
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|
| Extension Period |
|
|
All participants who received at least 1 dose of study treatment (ravulizumab or eculizumab).
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| ID | Title | Description |
|---|---|---|
| BG000 | Ravulizumab/Ravulizumab | On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 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 received weight-based doses of ravulizumab for up to 4 years. |
| BG001 | Eculizumab/Ravulizumab | Participants received 900 mg of eculizumab q2w for 26 weeks. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at first infusion of study drug | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). | Posted | Least Squares Mean | 95% Confidence Interval | percent change | Baseline, Day 183 |
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| Secondary | 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). | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). | Posted | Number | 95% Confidence Interval | number of participants | Baseline through Day 183 |
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| Secondary | 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. | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline, Day 183 |
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| Secondary | 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. | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through Day 183 |
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| Secondary | 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. | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through Day 183 |
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| Secondary | 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. | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | number of participants | Baseline through end of study (up to 4 years) |
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| Secondary | 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. | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, End of Study (up to 4 years) |
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| Secondary | 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. | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through end of study (up to 4 years) |
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| Secondary | 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. | Full Analysis Set: All participants who received at least 1 dose of randomized treatment (ravulizumab or eculizumab). Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through end of study (up to 4 years) |
|
|
From Baseline (after first dose) to end of study (up to 4 years)
Primary Evaluation Period (26 weeks)- Ravulizumab Treatment: data for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events are for participants in the Ravulizumab-Treated Set. Eculizumab Treatment: data for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events are for the participants in the Safety Set. Extension Period-data for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events are for the participants in the Ravulizumab-Treated Set.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Primary Evaluation Period (26 Weeks) Ravulizumab Treatment | On Day 1, participants received weight- based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. | 0 | 97 | 4 | 97 | 72 | 97 |
| EG001 | Primary Evaluation Period (26 Weeks) Eculizumab Treatment | Participants received 900 mg of eculizumab q2w for 26 weeks. | 0 | 98 | 8 | 98 | 85 | 98 |
| EG002 | Extension Period (Ravulizumab To Ravulizumab) | After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years. | 0 | 96 | 26 | 96 | 83 | 96 |
| EG003 | Extension Period (Eculizumab to Ravulizumab) | After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years. | 3 | 95 | 33 | 95 | 85 | 95 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemolysis | Blood and lymphatic system disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Pyelonephritis acute | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Aplastic anaemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Breakthrough haemolysis | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Pneumoperitoneum | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Biliary colic | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Liver disorder | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Escherichia sepsis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Pneumococcal infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Post procedural infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Suspected COVID-19 | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Ligament injury | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Cerebrospinal fluid retention | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Dupuytren's contracture | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Intervertebral disc degeneration | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Ureterolithiasis | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Liver function test increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Major depression | Psychiatric disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (25.0) | Systematic Assessment |
| |
| Endometrial cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (25.0) | Systematic Assessment |
| |
| Lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (25.0) | Systematic Assessment |
| |
| Renal cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (25.0) | Systematic Assessment |
| |
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (25.0) | Systematic Assessment |
| |
| Invasive papillary breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (25.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals Inc. | Alexion Pharmaceuticals Inc. | 855-752-2356 | clinicaltrials@alexion.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 12, 2017 | Feb 15, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006457 | Hemoglobinuria, Paroxysmal |
| ID | Term |
|---|---|
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009190 | Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000629409 | ravulizumab |
| C481642 | eculizumab |
Not provided
Not provided
Not provided
| Death |
|
| Withdrawal by Subject |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Not Reported |
|
| Black or African American |
|
| Unknown |
|
| Other |
|
| Multiple |
|
|
|
|
|
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| Participants |
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| Participants |
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