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The goal of the study was to evaluate the efficacy and safety of crizanlizumab in sickle cell disease (SCD) patients with priapism.
Before participating in this study, information to determine key eligibility criteria was collected as a part of a 14-week Pre-Screening period. The study included a 12-week Screening period and a 52-week (1 year) Treatment period. Eligible participants received crizanlizumab 5 mg/kg by intravenous infusion (IV). Study treatment was received at clinic visits on Week 1 Day 1, Week 3 Day 1, and then on Day 1 of every 4-week cycle. Efficacy assessments included evaluation of priapic and vaso-occlusive (VOC) events. Safety assessments included laboratory tests, electrocardiograms (ECGs), vital signs and physical examinations. Participants had a safety follow-up for up to 15 weeks after the last dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crizanlizumab 5 mg/kg | Experimental | Participants received 5 mg/kg by IV infusion on Week 1 Day 1, Week 3 Day 1, and on Day 1 of every 4-week cycle until Week 51. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Crizanlizumab | Drug | Crizanlizumab is a concentrate for solution for infusion, IV use. Supplied in single use 10 mL vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Priapic Events From Baseline to 26 Weeks | A priapic event was defined as an unwanted or painful penile erection lasting at least 60 minutes. Priapic events were self-reported via an electronic reporting system, and data was collected throughout the study period. Number of priapic events was summarized at Baseline (adjusted for 26 weeks) and by 26 weeks, and percent reduction from adjusted Baseline by 26 weeks was summarized. | Baseline up to 26 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Rate of Priapic Events | A priapic event was defined as an unwanted or painful penile erection lasting at least 60 minutes. Priapic events were self-reported via an electronic reporting system, and data was collected throughout the study period. The annualized rate of events was defined as the total number of events for a participant occurring from the date of initial infusion to the last contact date of the Treatment Phase of the study x 365.25 divided by the number of days during that same time period. The calculation accounted for early dropouts or lost to follow-up by extrapolating the priapism events rate of every participant to 1 year. |
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Inclusion criteria
Exclusion criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Of Alabama | Birmingham | Alabama | 35294 | United States | ||
| University of Connecticut Health Center |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
| A Pediatric Plain Language Trial Summary is available on www.novctrd.com | View source |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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| ID | Title | Description |
|---|---|---|
| FG000 | Crizanlizumab 5 mg/kg | Participants received 5 mg/kg by IV infusion on Week 1 Day 1, Week 3 Day 1, and on Day 1 of every 4-week cycle until Week 51. |
| 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 | Dec 16, 2022 | Nov 26, 2024 |
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| Baseline up to 26 and 52 weeks |
| Number of Acute Priapic Events From Baseline to 26 and 52 Weeks | An acute priapic event was defined as an unwanted, painful erection that lasted more than 4 hours and required a visit to the emergency room. | Baseline up to 26 and 52 weeks |
| Annualized Rate of Uncomplicated Vaso-occlusive Crises (VOCs) | An uncomplicated VOC event was defined as an acute event of pain with no known cause for pain other than a VOC event; and requiring treatment with a parenteral or oral opioids or other parenteral analgesic; but was NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism. Events included both healthcare and self-reported events. The annualized rate of events was defined as the total number of events for a participant occurring from the date of initial infusion to the last contact date of the Treatment Phase of the study x 365.25 divided by the number of days during that same time period. The calculation accounted for early dropouts or lost to follow-up by extrapolating the priapism events rate of every participant to 1 year. | Baseline up to 26 and 52 weeks |
| Annualized Rate of Complicated VOCs | Complicated VOCs were defined as acute chest syndrome, hepatic sequestration, splenic sequestration, and acute priapism recorded by healthcare visit. The annualized rate of events was defined as the total number of events for a participant occurring from the date of initial infusion to the last contact date of the Treatment Phase of the study x 365.25 divided by the number of days during that same time period. The calculation accounted for early dropouts or lost to follow-up by extrapolating the priapism events rate of every participant to 1 year. | Baseline up to 26 and 52 weeks |
| Farmington |
| Connecticut |
| 06030 |
| United States |
| Childrens National Hospital | Washington D.C. | District of Columbia | 20010 | United States |
| Foundation for Sickle Cell Disease Research | Hollywood | Florida | 33021 | United States |
| Emory University School of Medicine | Atlanta | Georgia | 30303 | United States |
| LSU Medical Center | Shreveport | Louisiana | 71130 | United States |
| Childrens Hosp Boston Dept of Hematology | Boston | Massachusetts | 02115 | United States |
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Brody School of Medicine | Greenville | North Carolina | 27834 | United States |
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213-2548 | United States |
| Prisma Health Upstate | Greenville | South Carolina | 29615 | United States |
| University of Texas Medical School | Houston | Texas | 77030 | United States |
| COMPLETED |
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| NOT COMPLETED |
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The Full Analysis Set (FAS) included all enrolled participants to whom the study treatment was assigned regardless of whether or not they had received at least one dose of study treatment or had at least one post-baseline assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Crizanlizumab 5 mg/kg | Participants received 5 mg/kg by IV infusion on Week 1 Day 1, Week 3 Day 1, and on Day 1 of every 4-week cycle until Week 51. |
| 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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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | 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 | Percent Change in Priapic Events From Baseline to 26 Weeks | A priapic event was defined as an unwanted or painful penile erection lasting at least 60 minutes. Priapic events were self-reported via an electronic reporting system, and data was collected throughout the study period. Number of priapic events was summarized at Baseline (adjusted for 26 weeks) and by 26 weeks, and percent reduction from adjusted Baseline by 26 weeks was summarized. | The full analysis set (FAS) included all enrolled participants to whom the study treatment was assigned regardless of whether or not they received at least one dose of study treatment or had at least one post-baseline assessment. | Posted | Median | Inter-Quartile Range | Percent change from baseline | Baseline up to 26 weeks |
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| Secondary | Annualized Rate of Priapic Events | A priapic event was defined as an unwanted or painful penile erection lasting at least 60 minutes. Priapic events were self-reported via an electronic reporting system, and data was collected throughout the study period. The annualized rate of events was defined as the total number of events for a participant occurring from the date of initial infusion to the last contact date of the Treatment Phase of the study x 365.25 divided by the number of days during that same time period. The calculation accounted for early dropouts or lost to follow-up by extrapolating the priapism events rate of every participant to 1 year. | The FAS included all enrolled participants to whom the study treatment was assigned regardless of whether or not they received at least one dose of study treatment or had at least one post-baseline assessment. | Posted | Median | Inter-Quartile Range | Events per year | Baseline up to 26 and 52 weeks |
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| Secondary | Number of Acute Priapic Events From Baseline to 26 and 52 Weeks | An acute priapic event was defined as an unwanted, painful erection that lasted more than 4 hours and required a visit to the emergency room. | The FAS included all enrolled participants to whom the study treatment was assigned regardless of whether or not they received at least one dose of study treatment or had at least one post-baseline assessment. Only participants with Acute Priapic Events are included in this analysis. | Posted | Median | Full Range | Number of acute priapic events | Baseline up to 26 and 52 weeks |
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| Secondary | Annualized Rate of Uncomplicated Vaso-occlusive Crises (VOCs) | An uncomplicated VOC event was defined as an acute event of pain with no known cause for pain other than a VOC event; and requiring treatment with a parenteral or oral opioids or other parenteral analgesic; but was NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism. Events included both healthcare and self-reported events. The annualized rate of events was defined as the total number of events for a participant occurring from the date of initial infusion to the last contact date of the Treatment Phase of the study x 365.25 divided by the number of days during that same time period. The calculation accounted for early dropouts or lost to follow-up by extrapolating the priapism events rate of every participant to 1 year. | The FAS included all enrolled participants to whom the study treatment was assigned regardless of whether or not they received at least one dose of study treatment or had at least one post-baseline assessment. Only participants who had uncomplicated VOC events within the specified time frame were included in the analysis. | Posted | Median | Inter-Quartile Range | Events per year | Baseline up to 26 and 52 weeks |
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| Secondary | Annualized Rate of Complicated VOCs | Complicated VOCs were defined as acute chest syndrome, hepatic sequestration, splenic sequestration, and acute priapism recorded by healthcare visit. The annualized rate of events was defined as the total number of events for a participant occurring from the date of initial infusion to the last contact date of the Treatment Phase of the study x 365.25 divided by the number of days during that same time period. The calculation accounted for early dropouts or lost to follow-up by extrapolating the priapism events rate of every participant to 1 year. | The FAS included all enrolled participants to whom the study treatment was assigned regardless of whether or not they received at least one dose of study treatment or had at least one post-baseline assessment. Only participants who had complicated VOC events within the specified time frame were included in the analysis. | Posted | Median | Inter-Quartile Range | Events per year | Baseline up to 26 and 52 weeks |
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| Post-Hoc | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Associated With Infusion Related Reactions (Adverse Events of Special Interest) | A TEAE was defined as an adverse event starting or worsening after the administration of study medication. TEAEs experienced by participants in association with infusion related reactions were classified as adverse events of special interest (AESIs). | The Safety Analysis Set consisted of all participants who received at least 1 dose of study treatment. | Posted | Count of Participants | Participants | Baseline up to 57 weeks |
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| Post-Hoc | Percent Change in Priapic Events From Baseline to 26 Weeks Without the Outlier | A priapic event was defined as an unwanted or painful penile erection lasting at least 60 minutes. Priapic events were self-reported via an electronic reporting system, and data was collected throughout the study period. Number of priapic events was summarized at Baseline (adjusted for 26 weeks) and by 26 weeks, and percent reduction from adjusted Baseline by 26 weeks was summarized. For one participant, the outlier, a large amount of data corresponding to 38 days of screening (45% of the period), was not reported. Additionally, data in the other days of the Screening Period were also not collected. This was a unique occurrence which did not happen with other participants. To understand its impact, the primary endpoint has also been analyzed excluding this outlier in a post-hoc sensitivity analysis. | The FAS included all enrolled participants to whom the study treatment was assigned regardless of whether or not they received at least one dose of study treatment or had at least one post-baseline assessment. Analysis was performed excluding one outlier participant, who had a large amount of data unreported. | Posted | Median | Inter-Quartile Range | Percent change from baseline | Baseline up to 26 weeks |
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Adverse events were reported from first dose of study treatment until end of study treatment, up to a maximum duration of 57 weeks.
The Safety Analysis Set consisted of all participants who received at least 1 dose of study treatment.
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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 | Crizanlizumab 5 mg/kg | Participants received 5 mg/kg by IV infusion on Week 1 Day 1, Week 3 Day 1, and on Day 1 of every 4-week cycle until Week 51. | 0 | 36 | 7 | 36 | 26 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Peripheral swelling | General disorders | MedDRA (26.1) | Systematic Assessment |
| |
| Periorbital cellulitis | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (26.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (26.1) | Systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA (26.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus bradycardia | Cardiac disorders | MedDRA (26.1) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (26.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (26.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (26.1) | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA (26.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (26.1) | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA (26.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (26.1) | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (26.1) | Systematic Assessment |
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| Amylase increased | Investigations | MedDRA (26.1) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (26.1) | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA (26.1) | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA (26.1) | Systematic Assessment |
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| Blood lactate dehydrogenase increased | Investigations | MedDRA (26.1) | Systematic Assessment |
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| Lymphocyte count increased | Investigations | MedDRA (26.1) | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA (26.1) | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (26.1) | Systematic Assessment |
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| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (26.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (26.1) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (26.1) | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (26.1) | Systematic Assessment |
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This was a single-arm trial in a disease where clinical history has significant variability.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 1 862 778 8300 | Novartis.email@Novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 20, 2024 | Nov 26, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011317 | Priapism |
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D010409 | Penile Diseases |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C000614139 | crizanlizumab |
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| Unknown or Not Reported |
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