2023-508689-14-00招募中3 期
A phase III, Multicenter, Randomized, Double-blind Study to Assess Efficacy and Safety of Two Doses of Crizanlizumab versus placebo, with or without Hydroxyurea/Hydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients with Vaso-Occlusive Crises (STAND)
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 31
- 试验地点
- 11
- 主要终点
- Annualized rate of VOC events leading to healthcare visit in each treatment group over the first year post randomization
研究概览
简要总结
To compare the efficacy of 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOC leading to healthcare visit, in addition to standard of care To compare the efficacy of 5.0 mg/kg of crizanlizumab versus placebo on the annualized rate of VOC leading to healthcare visit, in addition to standard of care
入排标准
- 年龄范围
- 0 years 至 65+ years（18-64 Years, 65+ Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •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. Adolescents include patients aged 12 to 17 years old and adults ≥ 18 years
- •Confirmed diagnosis of SCD by Hb 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:
- •Pain crisis defined as an acute onset of pain for which there is no other medically determined explanation other than vaso- occlusion
- •which requires a visit to a medical facility and/or healthcare professional,
- •and receipt of oral/parenteral opioids or parenteral nonsteroidal anti-inflammatory drug (NSAID) analgesics Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration will be considered VOC in this study
- •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: • Absolute Neutrophil Count ≥1.0 x 109/L • Platelet count ≥75 x 109/L • Hemoglobin: for adults (Hb) ≥4.0 g/dL and for adolescents (Hb) ≥5.5 g/dL • Glomerular filtration rate ≥ 45 mL/min/1.73 m2 using CKD-EPI formula in adults, and Shwartz formula in adolescents • Direct (conjugated) bilirubin < 2.0 x ULN • Alanine transaminase (ALT) < 3.0 x ULN
- •ECOG performance status ≤ 2.0 for adults and Karnofsky ≥ 50% for adolescents
排除标准
- •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: • Concomitant clinically significant cardiac arrhythmias (e.g ventricular tachycardia), and clinically significant second or third degree AV block without a pacemaker • History of familial long QT syndrome or know family history of Torsades de Pointes
- •Not able to understand and to comply with study instructions and requirements.
- •Received prior treatment with crizanlizumab or other selectin targeting agent
结局指标
主要结局
Annualized rate of VOC events leading to healthcare visit in each treatment group over the first year post randomization
Annualized rate of VOC events leading to healthcare visit in each treatment group over the first year post randomization
次要结局
- The time to first and second VOC calculated respectively as the time from date of randomization until the first and the second VOC leading to healthcare visit over the first year post randomization
- Annualized rate of visits to clinic, Emergency room (ER) and hospitalizations, both overall and VOC-related over the first year post randomization
- Evolution of albuminuria and ACR over the first year post randomization
- PK parameters after the first and fifth dose (e.g., AUC, Cmax, Tmax, half-life)
- PD parameter (P-selectin inhibition) after the first and fifth dose
- Annualized rate of VOCs leading to healthcare visit
- Annualized rate of all VOCs leading to healthcare visit and treated at home
- Annualized rate of VOCs managed at home
- Number, seriousness, severity, and causality assessments of treatment-emergent adverse events, including infections (serious, non-serious and opportunistic infections) and other safety data as considered appropriate
- Absolute change from baseline in hemoglobin
- Growth and sexual maturity assessment in adolescents (Tanner stage)
- Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab
- Annualized rate of all VOCs leading to healthcare visit and treated at home (based on documentation by health care provider following contact with participant) over the first year post randomization
- Annualized rate of VOCs managed at home over the first year post randomization
- Duration of VOCs leading to healthcare visit over the first year post randomization
- Number and percentage of participants free from VOCs leading to healthcare visit in each group over the first year post randomization
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (11)
Loading locations...
相似试验
招募中
3 期
A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults with Primary Progressive Multiple Sclerosis2023-505980-36-00F. Hoffmann-La Roche AG363
招募中
3 期
A study to compare Venetoclax Azacitidine and Quizartinib Vs Venetoclax and Azacitidine in newly diagnosed acute myeloid leukemia patient´s ineligible for standard induction chemotherapyAcute myeloid leukemia2025-522979-29-00Fundacion PETHEMA350
招募中
3 期
A trial to learn how well durvalumab and chemotherapy with or without tremelimumab work in adults with advanced cancer of the bladder or urinary system2024-510976-19-00AstraZeneca AB353
招募中
3 期
Ocrelizumab VErsus Rituximab off-Label at the Onset of Relapsing MS Disease (OVERLORD-MS)Multiple Sclerosis2024-510716-71-00Helse Bergen HF214
已完成
3 期
Tezepelumab Efficacy and Safety in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid Dependent Asthma2023-504648-33-00AstraZeneca AB76