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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003440-74 | EudraCT Number |
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The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ravulizumab | Experimental | Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eculizumab | Biological | Participants must have been prescribed and be receiving a stable dose of eculizumab 1200 milligrams (mg) every 2 weeks (q2w) for at least 3 months prior to the Screening Period. During the Screening Period, participants will continue to receive eculizumab 1200 mg q2w. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experienced Free C5-associated BTH | 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). | Baseline through Day 351 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experienced BTH | 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. | Baseline through Day 351 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
History of major adverse vascular events within 6 months of Day 1.
History of bone marrow transplantation.
Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.
Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening:
Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
More than 1 LDH value > 2 × ULN within the 6 months prior to Day 1.
Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening.
Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Study Site | Leeds | LS9 7TF | United Kingdom | |||
| Research Site |
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| Label | URL |
|---|---|
| Related Info | View source |
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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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| ID | Title | Description |
|---|---|---|
| FG000 | Ravulizumab | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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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 7, 2021 | Mar 12, 2024 |
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| Ravulizumab | Biological | During the Treatment Period, participants will receive a loading dose of ravulizumab on Day 1, followed by maintenance doses on Day 15 and every 8 weeks, administered by intravenous infusion. Ravulizumab loading and maintenance doses will be based on participants' body weight per approved dose regimen. |
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| Percent Change From Baseline in LDH at Day 351 | Baseline, Day 351 |
| Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion | Baseline through Day 351 |
| Percentage of Participants With Stabilized Hemoglobin | 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. | Baseline through Day 351 |
| Leeds |
| LS9 7TF |
| United Kingdom |
| Clinical Study Site | London | SE5 9RS | United Kingdom |
| Research Site | London | SE5 9RS | United Kingdom |
| Received at Least 1 Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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The full analysis set (FAS) included all participants who received at least 1 dose of ravulizumab.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ravulizumab | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | Percentage of Participants Who Experienced Free C5-associated BTH | 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 FAS included all participants who received at least 1 dose of ravulizumab. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through Day 351 |
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| Secondary | Percentage of Participants Who Experienced BTH | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through Day 351 |
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| Secondary | Percent Change From Baseline in LDH at Day 351 | The FAS included all participants who received at least 1 dose of ravulizumab. Here, 'Overall number of participants analyzed' = participants evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | percent change | Baseline, Day 351 |
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| Secondary | Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion | The FAS included all participants who received at least 1 dose of ravulizumab. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through Day 351 |
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| Secondary | Percentage of Participants With Stabilized Hemoglobin | 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. | The FAS included all participants who received at least 1 dose of ravulizumab. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through Day 351 |
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Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
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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) |
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| EG000 | Ravulizumab | 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. | 0 | 18 | 3 | 18 | 15 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Retinal haemorrhage | Eye disorders | MedDRA 24.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| SARS-CoV-2 test positive | Investigations | MedDRA 24.1 | Systematic Assessment |
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| Body temperature abnormal | Investigations | MedDRA 24.1 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA 24.1 | Systematic Assessment |
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| Nail ridging | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Neurodermatitis | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Chromaturia | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
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| Haemoglobinuria | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
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| Extravascular haemolysis | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals Inc. | Alexion Pharmaceuticals Inc. | 855-752-2356 | clinicaltrials@alexion.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 20, 2023 | Mar 12, 2024 | 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 |
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| ID | Term |
|---|---|
| C481642 | eculizumab |
| C000629409 | ravulizumab |
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| Newborns (0-27 days) |
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| Infants and toddlers (28 days-23 months) |
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| Children (2-11 years) |
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| Adolescents (12-17 years) |
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| Adults (18-64 years) |
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| From 65-84 years |
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| 85 years and over |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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