2024-513096-41-00已完成2 期
HEMolyse and Organ damage imPROvement in sickle cell disease by VoxElotor. An open-label one stage phase II design.HEMOPROVE
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Improvement of Intravascular hemolysis, as defined by a ≥20% decrease of plasma Hemoglobin (µmol/l) between W0 and W48 weeks
研究概览
简要总结
To evaluate the biological activity of Voxelotor on the reduction of intra vascular hemolysis measured by plasma hemoglobin
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •SS or S-β0 major sickle cell syndrome
- •Hemoglobin level < 9 g/dL
- •Aged 18 years or older
- •Stable dose for at least 3 months if treated with HU, EPO, angiotensin-converting enzyme (ACE), inhibitor/angiotensin receptor blocker (ARB), glutamine or crizanlizumab therapy; at least after 6 months after initiating HU treatment
- •Patient with social security
- •Female patient must have a negative serum pregnancy test (betaHCGat inclusion W0-V1D1) or evidence of post-menopausal status
- •Effective methods of birth control (e.g., condom, spermicidal gel, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring) or abstinence from screening through 4 weeks after last Voxelotor dose.
排除标准
- •Patients in chronic transfusion program or transfused < 3 months before enrolment
- •Chronic use of NSAIDs (more than 10 days by month)
- •Auto immune disease or infection not controlled or cancer
- •VIH, HBV, HCV current infection
- •Prior drug hypersensitivity to Voxelotor or excipients
- •Known allergy or hypersensitivity to imaging contrast product
- •Ongoing therapeutic study
- •If patient does not have any of the following treatments (HU, Crizanlizumab) he will then be excluded if: Patient meets, at screening, Hydroxyurea/ Crizanlizumab indications of treatment (recurrent painful vaso-occlusive crises, including acute chest syndrome), even if these treatments are inappropriate (e.g. hematologic toxicity antecedent) or if the patient refuses these treatments
- •Patient with severe organ involvement: hepatic (TP <50%), renal (eGFR<30 ml / ml/1.73m2 according to CKD/EPI or cardiac (LVEF <45%)
- •Transplant patients.
- •Breast feeding patients
- •Homeless patient
- •Patient deprived of liberty by judicial or administrative decision or patient under guardianship
- •Patient unable to understand the purpose and conditions of the study and unable to give consent
结局指标
主要结局
Improvement of Intravascular hemolysis, as defined by a ≥20% decrease of plasma Hemoglobin (µmol/l) between W0 and W48 weeks
Improvement of Intravascular hemolysis, as defined by a ≥20% decrease of plasma Hemoglobin (µmol/l) between W0 and W48 weeks
次要结局
- Blood viscosity
- Cerebral perfusion measured by MRI
- Evolution between W0 and W48 weeks in intravascular hemolysis, as measured by absolute and relative (%) changes from baseline in plasma Hemoglobin (µmol/l) and free plasma Heme (µmol/l)
- Measurement of total hemoglobin mass based on the CO rebreathing technique (g of Hb / kg), or a stable evolution (i.e. decrease ≤ 10%) in patients initially under EPO therapy and who decreased or discontinued EPO during the study period.
- RBC lifespan by measurement of alveolar CO (in days)
- Blood volumes by CO rebreathing method (Total Mass of Hemoglobin (g of Hb), Total blood volume (L), RBC mass (g), Plasma Volume (L) )
- Cerebral vaso-reactivity measured by transcranial Doppler (Breath holding test) and Near Infra Red Spectroscopy
- Cognitive performance measured by MoCA
- Improvement in the 6 minutes walk test on : Time spent under Sp02 88 and 90%, Borg Rating of Perceived Exertion (RPE), distance.
- Renal perfusion and amount of deoxyhemoglobin by MRI and Iron deposits in renal cortex by MRI
- Glomerular Filtration Rate measurements, urine concentration capacity (fasting urinary osmolarity)
- urine albumin/creatinine ratio
- Concomitant treatment observation: decrease / interruption of EPO dose
- Safety;(VOC, ACS, Priapism) presence/absence of each signs
- RBC properties: density, hemoglobin affinity , viscosity, deformability, senescence parameters, HbF/cell measure
- Blood lactate concentration during stress test (submaximal cardiopulmonary exercise test) and echocardiography during submaximal cardiopulmonary exercise test, at rest, ∼2 mmol.L-1 (LT1), ∼4 mmol.L-1 and during the recovery phase to evaluate parameters of left ventricular (LV) contractility, cardiac output and diastolic function
研究者
Gonzalo De Luna
Scientific
Assistance Publique Hopitaux De Paris
研究点 (2)
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