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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002674-20 | EudraCT Number |
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The primary purpose of this study is to evaluate the safety, tolerability, and efficacy of multiple intravenous (IV) doses of ravulizumab administered to complement inhibitor treatment-naïve participants with PNH.
The study consisted of a screening period of up to 30 days and a Treatment Period of up to 253 days for Cohorts 1-3 and 281 days for Cohort 4. After completion of the Treatment Period, all participants had the opportunity to enter the Extension Period, wherein participants continue to receive ravulizumab for up to 5 years. The first dose in the Extension Period occurred on Day 253 for Cohorts 1-3 and on Day 281 for Cohort 4.
The data presented includes the Primary Completion date of the study for the Treatment Period. The results for the Extension Period will be reported after study completion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | During the Treatment Period, participants were administered ravulizumab 1400 milligram (mg) on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kilograms (kg), 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
|
| Cohort 2 | Experimental | During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
|
| Cohort 3 | Experimental | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ravulizumab | Biological | All treatments were given as IV infusions. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change In LDH Levels From Baseline To Day 253 And Day 281 | The percent change in LDH levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281 | The percent change in free hemoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
| Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Toronto | Ontario | M4N 3M5 | Canada | ||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30171081 | Derived | Roth A, Rottinghaus ST, Hill A, Bachman ES, Kim JS, Schrezenmeier H, Terriou L, Urbano-Ispizua A, Wells RA, Jang JH, Kulasekararaj AG, Szer J, Aguzzi R, Damokosh AI, Shafner L, Lee JW. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies. Blood Adv. 2018 Sep 11;2(17):2176-2185. doi: 10.1182/bloodadvances.2018020644. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | During the Treatment Period, participants were administered ravulizumab 1400 milligrams (mg) on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kilograms (kg), 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment 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 | May 9, 2018 | Dec 7, 2022 |
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|
| Cohort 4 | Experimental | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
|
The percent change in haptoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. |
| Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
| Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281 | The percent change in reticulocyte/erythrocyte count levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
| Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253 | The percent change in paroxysmal nocturnal hemoglobinuria (PNH) red blood cell (RBC), summed types II and III, clone size levels were assessed from Baseline to Day 253 for Cohorts 1 to 4. | Baseline, Day 253 (Cohorts 1 to 4) |
| Percent Change In D-dimer From Baseline To Day 253 And Day 281 | The percent change in D-dimer levels were assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
| Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281 | Clinical manifestations were assessed from Baseline to Day 253 for Cohorts 1 to 3 and from Baseline to Day 281 for Cohort 4 only. Clinical manifestations were defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (male participants only). Improvement was defined as present at Baseline and absent at Day endpoint. Worsening was defined as absent at Baseline and present at Day endpoint. No Change was defined as no change from Baseline and time point of endpoint. | Baseline, Day 253 (Cohorts 1 to 3) and Day 281 (Cohort 4) |
| Lyon |
| Pierre-Bénite |
| 69495 |
| France |
| Clinical Trial Site | Lille | 59037 | France |
| Clinical Trial Site | Paris | 75475 | France |
| Clinical Trial Site | Ulm | Baden-Wurttemberg | 89081 | Germany |
| Clinical Trial Site | Aachen | North Rhine-Westphalia | 52074 | Germany |
| Clinical Trial Site | Essen | North Rhine-Westphalia | 45147 | Germany |
| Clinical Trial Site | Seoul | 03080 | South Korea |
| Clinical Trial Site | Seoul | 03722 | South Korea |
| Clinical Trial Site | Badalona | Barcelona | 08916 | Spain |
| Clinical Trial Site | Majadahonda | Madrid | 28220 | Spain |
| Clinical Trial Site | Barcelona | 08036 | Spain |
| Clinical Trial Site | Madrid | 28040 | Spain |
| Clinical Trial Site | Taipei | 10048 | Taiwan |
| Clinical Trial Site | Leeds | West Yorkshire | LS9 7TF | United Kingdom |
| Clinical Trial Site | London | SE5 9RS | United Kingdom |
| FG001 | Cohort 2 | During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| FG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| FG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
| Received at Least 1 Dose of Study Drug |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| Extension Period |
|
|
Safety set: All participants who received at least 1 dose of ravulizumab.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| BG001 | Cohort 2 | During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| BG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| BG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
| BG004 | 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 |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | Participants |
| ||||||||||||||||
| Lactate Dehydrogenase (LDH) Levels | Mean | Standard Deviation | units/liter (U/L) |
|
| 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 LDH Levels From Baseline To Day 253 And Day 281 | The percent change in LDH levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. Last observation carried forward (LOCF) was used for participants with a missing Day 253 or Day 281 assessment. | Posted | Mean | Standard Deviation | Percent Change | Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
|
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281 | The percent change in free hemoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF was used for participants with a missing Day 253 or Day 281 assessment. | Posted | Mean | Standard Deviation | Percent Change | Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
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| Secondary | Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281 | The percent change in haptoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF was used for participants with a missing Day 253 or Day 281 assessment. | Posted | Mean | Standard Deviation | Percent Change | Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281 | The percent change in reticulocyte/erythrocyte count levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF was used for participants with a missing Day 253 or Day 281 assessment. | Posted | Mean | Standard Deviation | Percent Change | Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
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| Secondary | Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253 | The percent change in paroxysmal nocturnal hemoglobinuria (PNH) red blood cell (RBC), summed types II and III, clone size levels were assessed from Baseline to Day 253 for Cohorts 1 to 4. | Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF was used for participants with a missing Day 253 assessment. | Posted | Mean | Standard Deviation | Percent Change | Baseline, Day 253 (Cohorts 1 to 4) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change In D-dimer From Baseline To Day 253 And Day 281 | The percent change in D-dimer levels were assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. | Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF is used for participants with a missing Day 253 or Day 281 assessment. | Posted | Mean | Standard Deviation | Percent Change | Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) |
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| Secondary | Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281 | Clinical manifestations were assessed from Baseline to Day 253 for Cohorts 1 to 3 and from Baseline to Day 281 for Cohort 4 only. Clinical manifestations were defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (male participants only). Improvement was defined as present at Baseline and absent at Day endpoint. Worsening was defined as absent at Baseline and present at Day endpoint. No Change was defined as no change from Baseline and time point of endpoint. | Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF is used for participants with a missing Day 253 or Day 281 assessment. Erectile dysfunction affects only male participants. | Posted | Count of Participants | Participants | Baseline, Day 253 (Cohorts 1 to 3) and Day 281 (Cohort 4) |
|
Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. | 0 | 6 | 3 | 6 | 6 | 6 |
| EG001 | Cohort 2 | During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. | 0 | 6 | 3 | 6 | 6 | 6 |
| EG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. | 0 | 7 | 4 | 7 | 7 | 7 |
| EG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. | 0 | 7 | 1 | 7 | 7 | 7 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Haemolysis | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Meningococcal infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Meningococcal sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Papillary thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Klebsiella bacteraemia | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Enterobacter bacteraemia | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Enterobacter sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Epididymitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Febrile infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Gonococcal infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Klebsiella sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Urinary tract infection bacterial | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Breakthrough haemolysis | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Large intestinal haemorrhage | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Biliary obstruction | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Post procedural complication | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiovascular disorder | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Haemoglobinuria | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Haemolysis | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ocular icterus | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals, Inc. | Alexion Pharmaceuticals, Inc. | +1-855-752-2356 | clinicaltrials@alexion.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 29, 2016 | Dec 7, 2022 | SAP_003.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 |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Not Reported |
|
| Other |
|
|
| Day 281 |
|
|
| Other |
| Statistical Analysis presented is of Cohort 4 at Day 281. A sample size of 20 participants from the combined cohorts was required to provide approximately 95% power to detect a mean paired difference in LDH from Baseline of -40% at Day 281 for Cohort 4 only, with an estimated SD of 45%. This was based on a 2-sided paired t-test, with 5% type I error rate. To account for a possible 15% dropout rate, up to 26 participants were enrolled. | MMRM | <0.0001 | Hypothesis testing was performed at the 0.05 level of significance. P-value tested whether the percent changes differed from 0. | 2-Sided | 95 | Other |
| OG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| OG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
|
|
|
| OG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| OG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
|
|
|
| OG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| OG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
|
|
|
| OG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| OG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
|
|
|
| OG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| OG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
|
|
|
| OG001 |
| Cohort 2 |
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| OG002 | Cohort 3 | During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more. |
| OG003 | Cohort 4 | During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years. |
|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
| Title | Measurements |
|---|---|
| Improved from Baseline |
|
| Worsened from Baseline |
|
| No Change |
|
| Not Applicable |
|
|
|