Estudio primario

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Crizanlizumab

Año 2018
Autores Kanter, J.
Revista Drugs of the Future
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Vaso-occlusive crises (VOCs; also known as sickle-cell-related pain crises [SCPCs]), which are the hallmark of sickle cell disease (SCD), can be precipitated by microvascular occlusion, increased inflammation and physical/emotional distress. De-spitethesubstantialburdenofmorbidityandmortalitycaused by VOCs, there is a paucity of approved preventive therapies that target the processes caused by SCD. Current options impose potential risk to the patient and have highly inconsistent therapeutic effects. Crizanlizumab is a first-in-class, recombinant, humanized monoclonal antibody that blocks interactions between P-selectin (a key VOC pathway modulator), and its ligand P-selectin glycoprotein ligand-1. Preclinical research has guided the initial clinical development of crizanlizumab, yielding insights into its pharmacokinetic/ pharmacodynamic profile and immunogenic properties in healthy volunteers. A phase II study demonstrated that crizanlizumab 5.0 mg/kg significantly lowers the rate of SCPCs versus placebo, and identified no unexpected safety findings. Current findings provide hope that crizanlizumab can deliver disease-modifying effects that prevent VOCs.

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Crizanlizumab for Treating COVID-19 Vasculopathy

Año 2020
Registro de estudios clinicaltrials.gov
Enlaces ClinicalTrials.gov

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The purpose of this trial is to test the efficacy and safety of crizanlizumab in patients hospitalized with COVID-19.

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Crizanlizumab to prevent crises in sickle cell disease

Año 2022
Autores Chaplin, S.
Revista Prescriber
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Estudio primario

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Study of Crizanlizumab for Prevention of Silent Cerebral Infarcts in SCA

Año 2022
Registro de estudios clinicaltrials.gov
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In this prospective, single-arm, open-label, imaging and treatment study, the investigator will test the hypothesis that crizanlizumab will prevent the progression of silent cerebral infarcts in patients with sickle cell disease. Study participants will undergo brain MRI before initiation of crizanlizumab and at 6 and 30 months after starting crizanlizumab infusions. The crizanlizumab cohort will be compared to a matched, observational cohort of patients not receiving crizanlizumab.

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Estudio primario

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Crizanlizumab for Treatment of Retinal Vasculopathy With Cerebral Leukoencephalopathy (RVCL)

Año 2021
Registro de estudios clinicaltrials.gov
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This is a Phase 2 trial that will test the efficacy and safety of crizanlizumab for the treatment of retinal vasculopathy with cerebral leukoencephalopathy (RVCL), a very rare and uniformly fatal genetic condition that affects the microvasculature, especially of the brain and eye. There currently is no treatment for RVCL. A maximum of 20 patients will be enrolled.

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Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease.

Año 2017
Revista The New England journal of medicine
Enlaces DOI , PMC , Pubmed
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<b>

BACKGROUND:

</b>The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease.<b>

METHODS:

</b>In this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed.<b>

RESULTS:

</b>A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain.<b>

CONCLUSIONS:

</b>In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .).

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Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases

Año 2023
Autores Sheba Medical Center
Registro de estudios clinicaltrials.gov
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A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.

Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:

Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.

Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.

Cohort 3: Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.

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Revisión sistemática

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Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis.

Año 2020
Autores Thom H , Jansen J , Shafrin J , Zhao L , Joseph G , Cheng HY - Más
Revista BMJ open
Enlaces DOI , PMC , Pubmed
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OBJECTIVES:

Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the efficacy and safety of crizanlizumab for older adolescent and adult (≥16 years old) SCD patients.

METHODS:

The SLR included randomised controlled trials (RCTs) and uncontrolled studies. Bayesian NMA of VOC, all-cause hospitalisation days and adverse events were conducted.

RESULTS:

The SLR identified 51 studies and 9 RCTs on 14 treatments that met the NMA inclusion criteria. The NMA found that crizanlizumab 5.0 mg/kg was associated with a reduction in VOC (HR 0.55, 95% credible interval (0.43, 0.69); Bayesian probability of superiority >0.99), all-cause hospitalisation days (0.58 (0.50, 0.68); >0.99) and no evidence of difference on adverse events (0.91 (0.59, 1.43) 0.66) or serious adverse events (0.93 (0.47, 1.87); 0.59) compared with placebo. The HR for reduction in VOC for crizanlizumab relative to L-glutamine was (0.67 (0.50, 0.88); >0.99). These results were sensitive to assumptions regarding whether patient age is an effect modifier.

CONCLUSIONS:

This NMA provides preliminary evidence comparing the efficacy of crizanlizumab with other treatments for VOC prevention.

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Estudio primario

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MAP to Provide Access to Crizanlizumab, for Sickle Cell Disease Patients

Año 2018
Autores Novartis
Registro de estudios clinicaltrials.gov
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The purpose of this Cohort Treatment Plan is to allow access to crizanlizumab (SEG101) for eligible patients diagnosed with sickle cell disease (SCD) to prevent or reduce the frequency of vaso-occlusive crises (VOC). The patient\'s Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations.

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Estudio primario

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The Effect of Crizanlizumab on Cerebral Perfusion and Oxygenation in Sickle Cell Patients

Año 2021
Autores Amsterdam UMC - AMC
Registro de estudios EU Clinical Trials Register
Enlaces EUCTR
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