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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-001746-10 | EudraCT Number |
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The purpose of this study is to compare the efficacy and safety of 2 doses of crizanlizumab (5.0 mg/kg and 7.5 mg/kg) versus placebo in adolescent and adult sickle cell disease (SCD) patients with history of vaso-occlusive crisis (VOC) leading to healthcare visit.
Study CSEG101A2301 (STAND) is an ongoing Phase III, multicenter, randomized, double-blind study to assess efficacy and safety of two doses of crizanlizumab (5 mg/kg and 7.5 mg/kg) versus placebo, with or without hydroxyurea/ hydroxycarbamide therapy (HU/HC), in adolescent and adult patients with SCD and history of VOC leading to healthcare visit.
This is a multicenter clinical trial comparing 2 doses of crizanlizumab (5 mg/kg and 7.5 mg/kg) versus placebo in addition to standard of care participants might be taking at the time of study start, in adolescent and adult participants with confirmed diagnosis of sickle cell disease (SCD) and history of vaso-occlusive crisis (VOC) leading to a healthcare visit.
240 participants (including 48 adolescents) were planned to be randomized in a 1:1:1 ratio to either 5 mg/kg, 7.5 mg/kg of crizanlizumab or placebo. Randomized participants were stratified by concomitant HU/HC usage (yes/no) and baseline rate of VOCs leading to a healthcare visit in 12 months prior to screening visit (2-4 vs. ≥ 5 VOCs) at the time of enrollment. In November 2020, a capping of 90 adult participants per strata was implemented to ensure adequate opportunity for enrollment into each of the 4 strata.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crizanlizumab (SEG101) at 5.0 mg/kg | Experimental | Participants received Crizanlizumab (SEG101) at 5.0 mg/kg |
|
| Crizanlizumab (SEG101) at 7.5 mg/kg | Experimental | Participants received Crizanlizumab (SEG101) at 7.5 mg/kg |
|
| Placebo | Placebo Comparator | Participants received the placebo drug. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Crizanlizumab (SEG101) | Drug | Crizanlizumab was supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. This is a concentrate for solution for infusion. IV. |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to a Healthcare Visit | VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit is defined as any visit to a medical facility such as emergency room (ER), hospital and/or office visit, which includes pain management of VOC in situ. Annualized rate of corresponding VOC events = (Number of corresponding VOC events * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days). | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over the First-year Post Randomization (Key Secondary) | VOCs are based on documentation by provider following contact with participant. VOC:pain crisis requiring therapy with oral/parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome, priapism and hepatic or splenic sequestration. Healthcare visit:a visit to a medical facility (ER, hospital &/or office visit resulting in pain management of VOC. Managed at home: no visit to any medical facility &/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice is allowed. Annualized rate of corresponding VOC events = (# of corresponding VOC events * 365)/(# of days in observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor & erythropoietin therapies to treat SCD &/or to prevent/reduce VOCs), date of randomization + 365 days) |
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Key Inclusion Criteria:
Written informed consent must be obtained prior to any screening procedures
Male or female patients aged 12 years and older on the day of signing informed consent. Adolescent include patients aged 12 to 17 years old and adults ≥ 18 years
Confirmed diagnosis of SCD by hemoglobin electrophoresis or high performance liquid chromatography (HPLC) [performed locally]. All SCD genotypes are eligible, genotyping is not required for study entry
Experienced at least 2 VOCs leading to healthcare visit within the 12 months prior to screening visit as determined by medical history. Prior VOC leading to healthcare visit must resolve at least 7 days prior to Week 1 Day 1 and must include:
If receiving HU/HC or L-glutamine (local HA approved medicinal product), must have been receiving the drug for at least 6 months and at a stable dose for at least 3 months prior to Screening visit and plan to continue taking it at the same dose and schedule until the subject has reached one year of study treatment. Patients who have not been receiving such drug must not have received it for at least 6 months prior to Screening visit to be included. Patients must have evidence of insufficient control of acute pain, such as at least one VOC leading to healthcare visit while on HU/HC or L-Glutamine treatment. If receiving erythropoietin stimulating agent, must have been receiving the drug for at least 6 months prior to Screening visit and plan to continue taking the treatment to maintain stable Hb levels at least until the subject has reached one year of study treatment
Patients must meet the following central laboratory values prior to Week 1 Day 1:
ECOG performance status ≤2.0 for adults and Karnofsky ≥ 50% for adolescents
Key Exclusion Criteria:
History of stem cell transplant.
Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted.
Contraindication or hypersensitivity to any drug or metabolites from similar class as study drug or to any excipients of the study drug formulation. History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
Received active treatment on another investigational trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to Screening visit or plans to participate in another investigational drug trial.
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception during dosing and for 15 weeks after stopping treatment.
Concurrent severe and/or uncontrolled medical conditions which, in the opinion of the Investigator, could cause unacceptable safety risks or compromise participation in the study.
History or current diagnosis of ECG abnormalities indicating significant risk of safety such as:
Not able to understand and to comply with study instructions and requirements.
Received prior treatment with crizanlizumab or other selectin targeting agent
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Childrens Healthcare of Atlanta | Atlanta | Georgia | 30342 | United States | ||
| Boston Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40088922 | Derived | Abboud MR, Cancado RD, De Montalembert M, Smith WR, Rimawi H, Voskaridou E, Guvenc B, Ataga KI, Keefe D, Grosch K, Watson J, Reshetnyak E, Nassin ML, Dei-Adomakoh Y. Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial. Lancet Haematol. 2025 Apr;12(4):e248-e257. doi: 10.1016/S2352-3026(24)00384-3. Epub 2025 Mar 12. | |
| 37254256 |
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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 review 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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Screening assessments were done within 1 to 28 days prior to Week 1 Day 1. Re-screening of subjects was only allowed if the subject was not randomized before.
240 participants (including 48 adolescents) were planned to be randomized in a 1:1:1 ratio to either 5 mg/kg, 7.5 mg/kg of crizanlizumab or placebo. This study was conducted in 21 countries and 63 centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Crizanlizumab (SEG101) at 5.0 mg/kg | Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter. |
| FG001 | Crizanlizumab (SEG101) at 7.5 mg/kg |
| 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 | Mar 5, 2021 | Aug 31, 2023 |
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Double-blind Study
|
| Placebo | Drug | Placebo was supplied in single use 10 mL glass vials at a concentration of 0 mg/mL. This is a concentrate for solution for infusion IV. |
|
| 1 year |
| Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over 5 Years Post Randomization (Key Secondary) | To compare the efficacy of 5.0 mg/kg vs placebo & 7.5 mg/kg vs placebo on the annualized rate of all VOCs based on documentation by provider following contact with participant. VOC is defined as pain crisis (an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) requiring therapy with oral/parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome, priapism and hepatic or splenic sequestration. Healthcare visit is defined as a visit to a medical facility (emergency room, hospital and/or office visit resulting in pain management of VOC. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice is allowed. The annualized rate of VOC leading to healthcare visit is the number of VOC leading to healthcare visit multiplied by 365 & divided by the number of days in observation period. | 5 years |
| Mean Duration of VOCs Leading to a Healthcare Visit Over the First-year Post Randomization | To assess the duration of VOCs leading to healthcare visit in each group. Mean duration of VOC per participant is defined as the average duration of all individual episodes of VOCs leading to healthcare visits of a given participant (a VOC duration is defined as end date of the VOC - start date of the VOC + 1). Participants with no VOC leading to healthcare visits have been excluded. | 1 year |
| Number of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization | To assess the number of participants free from VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. A participant is free from VOC if they do not have a VOC crisis. | 1 year |
| Percentage of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization | To assess the percentage of participants free from VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. A participant is free from VOC if they do not have a VOC crisis. | 1 year |
| Time to First and Second VOCs Leading to a Healthcare Visit Over the First-year Post Randomization | To assess the time to first and second VOC leading to healthcare visit in each group. Time to first occurrence of VOC leading to a healthcare visit is defined as the time from the date of randomization to the date of the first occurrence of the VOC. Time to second occurrence of VOC leading to a healthcare visit is defined as the time from date of randomization to the date of the second occurrence of VOC. | 1 year |
| Annualized Rate of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization | To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC-related in each group. Annualized rate of corresponding healthcare visits =(Number of corresponding healthcare visits * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days) | 1 year |
| Annualized Days of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization | To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC-related in each group. Annualized days of corresponding healthcare visits =(Number of days =(Number of days of corresponding healthcare visits * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days). | 1 year |
| Evolution of Albumin Creatinine Ratio (ACR) Over the First-year Post-randomization (Change From Baseline) | Laboratory values for parameters related to renal function (creatinine, estimated glomerular filtration rate, urine microalbumin, and urine albumin/creatinine ratio) were measured at 6-month intervals over time from baseline. | Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1) |
| Evolution of Albuminuria (Urine Microalbumin) Over the First-year Post-randomization (Change From Baseline) | Laboratory values for parameters related to renal function (creatinine, estimated glomerular filtration rate, urine microalbumin, and urine albumin/creatinine ratio) were measured at 6-month intervals over time from baseline. | Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1) |
| Pharmacokinetic (PK) Profile of Crizanlizumab: AUCd15, AUCtau | To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Area under the (concentration-time profile) curve. | AUCd15 (first-dose) was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) to W3D1; AUCtau (steady-state) was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1 |
| PK Profile of Crizanlizumab: Cmax | To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Maximum concentration. | first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1 |
| PK Profile of Crizanlizumab: Tmax | To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Time to maximum concentration. | first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1 |
| PK Profile of Crizanlizumab: Half-life | To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: half life. | steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1 |
| PD Parameter (P-selectin Inhibition) | To characterize the pharmacodynamic (PD) of crizanlizumab at 5.0 and 7.5 mg/kg: P-selectin inhibition (% inhibition multipled by hr) | AUCd15 (first dose): W1D1, W1D2, W1D4, W2D1 and W3D1; steady state: W15D1, W15D2, W15D4, W16D1, W17D1 W18D1 and W19D1 |
| Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 1 Year | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit. VOC is defined as pain crisis which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit: any visit to a medical facility such as ER, hospital and/or office visit, which includes pain management of VOC in situ. Annualized rate of corresponding VOC events = (Number of corresponding VOC events * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days). | 1 year |
| Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 5 Years | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit is defined as any visit to a medical facility such as emergency room, hospital and/or office visit, which includes pain management of VOC in situ. The annualized rate of VOC leading to healthcare visit is the number of VOC leading to healthcare visit multiplied by 365 and divided by the number of days in the observation period. | 5 years |
| Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home at 5 Years | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the rates of all VOCs (managed at home + leading to healthcare visit). | 5 years |
| Number of VOCs Managed at Home at Year 1 | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the number of VOC events that were managed at home. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice was allowed. | 1 year |
| Number of VOCs Managed at Home at 5 Years | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the number of VOC events that were managed at home. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice was allowed. | 5 years |
| Absolute Change From Baseline in Hemoglobin | To assess safety of crizanlizumab over the study period. | 5 years |
| Growth and Sexual Maturity Assessment in Adolescents (Tanner Stage) | To assess safety of crizanlizumab over the study period. | 5 years |
| Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | To assess immunogenicity of crizanlizumab over the study period. | 5 years |
| Boston |
| Massachusetts |
| 02118 |
| United States |
| Levine Cancer Insitute Carolinas Healthcare System | Charlotte | North Carolina | 28204 | United States |
| Univ of Tenn Health Sciences Ctr | Memphis | Tennessee | 38163 | United States |
| U of TX Health Science Ct | Houston | Texas | 77030 | United States |
| Novartis Investigative Site | Brussels | Brussels Capital | 1070 | Belgium |
| Novartis Investigative Site | Brussels | 1000 | Belgium |
| Novartis Investigative Site | Edegem | 2650 | Belgium |
| Novartis Investigative Site | Salvador | Estado de Bahia | 41253-190 | Brazil |
| Novartis Investigative Site | Belém | Pará | 66033 000 | Brazil |
| Novartis Investigative Site | Recife | Pernambuco | 50070-170 | Brazil |
| Novartis Investigative Site | Rio de Janeiro | Rio de Janeiro | 20211-030 | Brazil |
| Novartis Investigative Site | Porto Alegre | Rio Grande do Sul | 90035-003 | Brazil |
| Novartis Investigative Site | Ribeirão Preto | São Paulo | 14048-900 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 01232-010 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 05403 000 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 08270-070 | Brazil |
| Novartis Investigative Site | Toronto | Ontario | M5G 2C4 | Canada |
| Novartis Investigative Site | Montreal | Quebec | H2X 1R9 | Canada |
| Novartis Investigative Site | Barranquilla | Atlántico | 080020 | Colombia |
| Novartis Investigative Site | Valledupar | Cesar Department | 200001 | Colombia |
| Novartis Investigative Site | Montería | 230004 | Colombia |
| Novartis Investigative Site | Helsinki | FIN 00290 | Finland |
| Novartis Investigative Site | Créteil | 94010 | France |
| Novartis Investigative Site | Marseille | 13885 | France |
| Novartis Investigative Site | Paris | 75015 | France |
| Novartis Investigative Site | Stuttgart | Baden-Wurttemberg | 70376 | Germany |
| Novartis Investigative Site | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Novartis Investigative Site | Berlin | 13353 | Germany |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Accra | GA-270-9830 | Ghana |
| Novartis Investigative Site | Athens | 115 27 | Greece |
| Novartis Investigative Site | Pátrai | 265 04 | Greece |
| Novartis Investigative Site | Thessaloniki | 54636 | Greece |
| Novartis Investigative Site | Bhubaneswar | Odisha | 751003 | India |
| Novartis Investigative Site | Hyderabad | Telangana | 500082 | India |
| Novartis Investigative Site | Genova | GE | 16128 | Italy |
| Novartis Investigative Site | Milan | MI | 20122 | Italy |
| Novartis Investigative Site | Verona | VR | 37134 | Italy |
| Novartis Investigative Site | Naples | 80138 | Italy |
| Novartis Investigative Site | Irbid | 22110 | Jordan |
| Novartis Investigative Site | Beirut | 113-0236 | Lebanon |
| Novartis Investigative Site | Tripoli | 1434 | Lebanon |
| Novartis Investigative Site | Amsterdam | North Holland | 1105 AZ | Netherlands |
| Novartis Investigative Site | Rotterdam | South Holland | 3015 GD | Netherlands |
| Novartis Investigative Site | The Hague | South Holland | 2545 AA | Netherlands |
| Novartis Investigative Site | Khoudh | 123 | Oman |
| Novartis Investigative Site | Panama City | Republica de Panama | 0801 | Panama |
| Novartis Investigative Site | Panama City | 0801 | Panama |
| Novartis Investigative Site | Soweto | Gauteng | 2013 | South Africa |
| Novartis Investigative Site | Barcelona | 08035 | Spain |
| Novartis Investigative Site | Madrid | 28034 | Spain |
| Novartis Investigative Site | Madrid | 28046 | Spain |
| Novartis Investigative Site | Adana | Saricam | 01330 | Turkey (Türkiye) |
| Novartis Investigative Site | Sheffield | South Yorkshire | S10 2JF | United Kingdom |
| Novartis Investigative Site | Cambridge | CB2 0QQ | United Kingdom |
| Novartis Investigative Site | London | SE1 9RT | United Kingdom |
| Novartis Investigative Site | London | SE5 9RS | United Kingdom |
| Novartis Investigative Site | Sheffield | S10 2TH | United Kingdom |
| Derived |
| Obadina M, Wilson S, Derebail VK, Little J. Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations. Kidney360. 2023 Jul 1;4(7):997-1005. doi: 10.34067/KID.0000000000000162. Epub 2023 May 31. |
Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.
| FG002 | Placebo | Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter. |
| COMPLETED | Completed = Ongoing |
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| NOT COMPLETED |
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The FAS comprises all participants to whom study treatment has been assigned by randomization.
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| ID | Title | Description |
|---|---|---|
| BG000 | Crizanlizumab (SEG101) at 5.0 mg/kg | Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter. |
| BG001 | Crizanlizumab (SEG101) at 7.5 mg/kg | Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter. |
| BG002 | Placebo | Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter. |
| BG003 | Total | Total of all reporting groups |
| 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, Customized | Number | 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/Ethnicity, Customized | Number | 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to a Healthcare Visit | VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit is defined as any visit to a medical facility such as emergency room (ER), hospital and/or office visit, which includes pain management of VOC in situ. Annualized rate of corresponding VOC events = (Number of corresponding VOC events * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days). | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Mean | Standard Deviation | number of events per year | 1 year |
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| Secondary | Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over the First-year Post Randomization (Key Secondary) | VOCs are based on documentation by provider following contact with participant. VOC:pain crisis requiring therapy with oral/parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome, priapism and hepatic or splenic sequestration. Healthcare visit:a visit to a medical facility (ER, hospital &/or office visit resulting in pain management of VOC. Managed at home: no visit to any medical facility &/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice is allowed. Annualized rate of corresponding VOC events = (# of corresponding VOC events * 365)/(# of days in observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor & erythropoietin therapies to treat SCD &/or to prevent/reduce VOCs), date of randomization + 365 days) | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Mean | Standard Deviation | number of events per year | 1 year |
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| Secondary | Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over 5 Years Post Randomization (Key Secondary) | To compare the efficacy of 5.0 mg/kg vs placebo & 7.5 mg/kg vs placebo on the annualized rate of all VOCs based on documentation by provider following contact with participant. VOC is defined as pain crisis (an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) requiring therapy with oral/parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome, priapism and hepatic or splenic sequestration. Healthcare visit is defined as a visit to a medical facility (emergency room, hospital and/or office visit resulting in pain management of VOC. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice is allowed. The annualized rate of VOC leading to healthcare visit is the number of VOC leading to healthcare visit multiplied by 365 & divided by the number of days in observation period. | Not Posted | Dec 2027 | 5 years | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Duration of VOCs Leading to a Healthcare Visit Over the First-year Post Randomization | To assess the duration of VOCs leading to healthcare visit in each group. Mean duration of VOC per participant is defined as the average duration of all individual episodes of VOCs leading to healthcare visits of a given participant (a VOC duration is defined as end date of the VOC - start date of the VOC + 1). Participants with no VOC leading to healthcare visits have been excluded. | The FAS comprises all participants to whom study treatment has been assigned by randomization. Participants with no VOC leading to healthcare visits are excluded. | Posted | Mean | Standard Deviation | days | 1 year |
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| Secondary | Number of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization | To assess the number of participants free from VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. A participant is free from VOC if they do not have a VOC crisis. | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Number | Participants | 1 year |
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| Secondary | Percentage of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization | To assess the percentage of participants free from VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. A participant is free from VOC if they do not have a VOC crisis. | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Number | Percentage of participants | 1 year |
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| Secondary | Time to First and Second VOCs Leading to a Healthcare Visit Over the First-year Post Randomization | To assess the time to first and second VOC leading to healthcare visit in each group. Time to first occurrence of VOC leading to a healthcare visit is defined as the time from the date of randomization to the date of the first occurrence of the VOC. Time to second occurrence of VOC leading to a healthcare visit is defined as the time from date of randomization to the date of the second occurrence of VOC. | The FAS comprises all participants to whom study treatment has been assigned by randomization. The estimated time to first and second VOC using Kaplan-Meier analyzed all participants, including those who experienced first (n=59, 52, 51) and second (n=41, 33, 33) events in 5mg/kg, 7.5mg/kg and placebo arms, respectively, those who were at risk, and those who were censored. | Posted | Median | 95% Confidence Interval | Months | 1 year |
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| Secondary | Annualized Rate of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization | To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC-related in each group. Annualized rate of corresponding healthcare visits =(Number of corresponding healthcare visits * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days) | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Mean | Standard Deviation | number of events per year | 1 year |
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| Secondary | Annualized Days of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization | To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC-related in each group. Annualized days of corresponding healthcare visits =(Number of days =(Number of days of corresponding healthcare visits * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days). | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Mean | Standard Deviation | number of days per year | 1 year |
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| Secondary | Evolution of Albumin Creatinine Ratio (ACR) Over the First-year Post-randomization (Change From Baseline) | Laboratory values for parameters related to renal function (creatinine, estimated glomerular filtration rate, urine microalbumin, and urine albumin/creatinine ratio) were measured at 6-month intervals over time from baseline. | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Median | Full Range | g/mol | Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1) |
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| Secondary | Evolution of Albuminuria (Urine Microalbumin) Over the First-year Post-randomization (Change From Baseline) | Laboratory values for parameters related to renal function (creatinine, estimated glomerular filtration rate, urine microalbumin, and urine albumin/creatinine ratio) were measured at 6-month intervals over time from baseline. | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Median | Full Range | g/L | Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1) |
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| Secondary | Pharmacokinetic (PK) Profile of Crizanlizumab: AUCd15, AUCtau | To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Area under the (concentration-time profile) curve. | Pharmacokinetic analysis set 1 includes all participants who provided at least one evaluable PK profile: received the planned treatment at 5 mg/kg or 7.5 mg/kg before single dose PK profile or 3 consecutive doses of the planned treatment before the multiple dose PK profile for the multiple dose PK profile; provided at least one PK parameter; did not have any transfusion of blood product in the last 4 weeks before the first PK sample of the full PK profile, or during the full PK profile. | Posted | Mean | Standard Deviation | hr*ug/mL | AUCd15 (first-dose) was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) to W3D1; AUCtau (steady-state) was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1 |
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| Secondary | PK Profile of Crizanlizumab: Cmax | To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Maximum concentration. | Pharmacokinetic analysis set 1 includes all participants who provided at least one evaluable PK profile: received the planned treatment at 5 mg/kg or 7.5 mg/kg before single dose PK profile or 3 consecutive doses of the planned treatment before the multiple dose PK profile for the multiple dose PK profile; provided at least one PK parameter; did not have any transfusion of blood product in the last 4 weeks before the first PK sample of the full PK profile, or during the full PK profile. | Posted | Mean | Standard Deviation | ug/mL | first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1 |
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| Secondary | PK Profile of Crizanlizumab: Tmax | To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Time to maximum concentration. | Pharmacokinetic analysis set 1 includes all participants who provided at least one evaluable PK profile: received the planned treatment at 5 mg/kg or 7.5 mg/kg before single dose PK profile or 3 consecutive doses of the planned treatment before the multiple dose PK profile for the multiple dose PK profile; provided at least one PK parameter; did not have any transfusion of blood product in the last 4 weeks before the first PK sample of the full PK profile, or during the full PK profile. | Posted | Median | Full Range | hr | first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1 |
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| Secondary | PK Profile of Crizanlizumab: Half-life | To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: half life. | Pharmacokinetic analysis set 1 includes all participants who provided at least one evaluable PK profile: received the planned treatment at 5 mg/kg or 7.5 mg/kg before single dose PK profile or 3 consecutive doses of the planned treatment before the multiple dose PK profile for the multiple dose PK profile; provided at least one PK parameter; did not have any transfusion of blood product in the last 4 weeks before the first PK sample of the full PK profile, or during the full PK profile. | Posted | Mean | Standard Deviation | day | steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1 |
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| Secondary | PD Parameter (P-selectin Inhibition) | To characterize the pharmacodynamic (PD) of crizanlizumab at 5.0 and 7.5 mg/kg: P-selectin inhibition (% inhibition multipled by hr) | The Pharmacodynamic analysis set 1 includes all participants who provided at least 1 evaluable PD profile: received planned treatment of crizanlizumab at 5 mg/kg or 7.5 mg/kg before single dose PD profile or 3 consecutive doses of planned treatment before the multiple dose PD profile; provided at least 1 PD-AUC (single dose or multiple dose) parameter; did not have any transfusion of blood product in the last 4 weeks before the first PD sample of the full PD profile or during the full PD profile | Posted | Mean | Standard Deviation | h * % | AUCd15 (first dose): W1D1, W1D2, W1D4, W2D1 and W3D1; steady state: W15D1, W15D2, W15D4, W16D1, W17D1 W18D1 and W19D1 |
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| Secondary | Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 1 Year | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit. VOC is defined as pain crisis which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit: any visit to a medical facility such as ER, hospital and/or office visit, which includes pain management of VOC in situ. Annualized rate of corresponding VOC events = (Number of corresponding VOC events * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days). | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Mean | Standard Deviation | number of events per year | 1 year |
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| Secondary | Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 5 Years | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit is defined as any visit to a medical facility such as emergency room, hospital and/or office visit, which includes pain management of VOC in situ. The annualized rate of VOC leading to healthcare visit is the number of VOC leading to healthcare visit multiplied by 365 and divided by the number of days in the observation period. | Not Posted | Dec 2027 | 5 years | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home at 5 Years | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the rates of all VOCs (managed at home + leading to healthcare visit). | Not Posted | Dec 2027 | 5 years | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of VOCs Managed at Home at Year 1 | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the number of VOC events that were managed at home. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice was allowed. | The FAS comprises all participants to whom study treatment has been assigned by randomization. | Posted | Number | total number of VOC events | 1 year |
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| Secondary | Number of VOCs Managed at Home at 5 Years | To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the number of VOC events that were managed at home. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice was allowed. | Not Posted | Dec 2027 | 5 years | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Absolute Change From Baseline in Hemoglobin | To assess safety of crizanlizumab over the study period. | Not Posted | Dec 2027 | 5 years | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Growth and Sexual Maturity Assessment in Adolescents (Tanner Stage) | To assess safety of crizanlizumab over the study period. | Not Posted | Dec 2027 | 5 years | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab | To assess immunogenicity of crizanlizumab over the study period. | Not Posted | Dec 2027 | 5 years | Participants |
This primary analysis report includes data with a cut-off date 31-Aug-2022. Adverse events and deaths were collected from first dose of study treatment to105 days post-last infusion (defined as on-treatment), up to max on-treatment period of approx. 5 years.
Any sign or symptom that occurs during the conduct of the trial and safety follow-up.
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 | Crizanlizumab (SEG101) at 5.0 mg/kg (On-treatment) | AEs during on-treatment period (up to 105 days post-last infusion) | 2 | 84 | 35 | 84 | 67 | 84 |
| EG001 | Crizanlizumab (SEG101) at 7.5 mg/kg (On-treatment) | AEs during on-treatment period (up to 105 days post-last infusion) | 2 | 83 | 22 | 83 | 71 | 83 |
| EG002 | Placebo (On-treatment) | AEs during on-treatment period (up to 105 days post-last infusion) | 2 | 85 | 26 | 85 | 66 | 85 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
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| Bone marrow necrosis | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
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| Haemolysis | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
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| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
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| Sickle cell anaemia with crisis | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
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| Bradycardia | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
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| Cardiac disorder | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
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| Pulmonary valve stenosis | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
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| Sickle cell anaemia | Congenital, familial and genetic disorders | MedDRA (25.1) | Systematic Assessment |
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| Epiretinal membrane | Eye disorders | MedDRA (25.1) | Systematic Assessment |
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| Vitreous haemorrhage | Eye disorders | MedDRA (25.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Inflammatory bowel disease | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Lip swelling | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Pancreatitis acute | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Chills | General disorders | MedDRA (25.1) | Systematic Assessment |
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| Pain | General disorders | MedDRA (25.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (25.1) | Systematic Assessment |
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| Ulcer | General disorders | MedDRA (25.1) | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | MedDRA (25.1) | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA (25.1) | Systematic Assessment |
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| Cholestasis | Hepatobiliary disorders | MedDRA (25.1) | Systematic Assessment |
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| Hepatic failure | Hepatobiliary disorders | MedDRA (25.1) | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (25.1) | Systematic Assessment |
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| Hypersensitivity | Immune system disorders | MedDRA (25.1) | Systematic Assessment |
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| Abscess neck | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Arthritis bacterial | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| COVID-19 pneumonia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Dengue fever | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Device related infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Escherichia bacteraemia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Klebsiella infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Osteomyelitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Septic shock | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Staphylococcal bacteraemia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Staphylococcal infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Urosepsis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Haemolytic transfusion reaction | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
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| SARS-CoV-2 test positive | Investigations | MedDRA (25.1) | Systematic Assessment |
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| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Axial spondyloarthritis | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Fibromyalgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Myositis | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Carotid artery aneurysm | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
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| Embolic stroke | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
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| Haemorrhage intracranial | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
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| Intracranial aneurysm | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
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| Neuralgia | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
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| Substance-induced psychotic disorder | Psychiatric disorders | MedDRA (25.1) | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA (25.1) | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA (25.1) | Systematic Assessment |
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| Renal impairment | Renal and urinary disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Haemorrhagic ovarian cyst | Reproductive system and breast disorders | MedDRA (25.1) | Systematic Assessment |
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| Pelvic pain | Reproductive system and breast disorders | MedDRA (25.1) | Systematic Assessment |
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| Priapism | Reproductive system and breast disorders | MedDRA (25.1) | Systematic Assessment |
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| Acute chest syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Acute pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Emphysema | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hip arthroplasty | Surgical and medical procedures | MedDRA (25.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Sickle cell anaemia with crisis | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
|
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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 13, 2021 | Aug 31, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D000098644 | Vaso-Occlusive Crises |
| D006402 | Hematologic Diseases |
| D012805 | Sickle Cell Trait |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| C000614139 | crizanlizumab |
Not provided
Not provided
Not provided
| 18 - < 65 years |
|
| 65 - < 85 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| White |
|
| Asian |
|
| American Indian or Alaska Native |
|
| Multiple (White and Black or African American) |
|
| Unknown |
|
| Rate ratio |
| 0.89 |
| 2-Sided |
| 95 |
| 0.62 |
| 1.27 |
| Superiority |
Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter. |
| OG002 | Placebo | Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter. |
|
|
|
|
|
|
|
|
|
Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter. |
|
|
|
Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter. |
|
|
|
| Placebo |
Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter. |
|
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Participants |
|
|
| Participants |
|
|
Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.
| OG002 | Placebo | Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter. |
|
|
Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter.
|
|