A Study of Efficacy and Safety of FXS6837 in Anti-C5 Treated PNH Patients.
A Multicenter, Single-Arm, Open-Label Phase III Clinical Study Evaluating the Efficacy and Safety of FXS6837 Capsules in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Remain Anemic After Previous Stable Use of the C5 Complement Inhibitor
This is an single arm, open label designed phase III study to evaluate the efficacy and safety of oral FXS6837 capsules in PNH patients with residual anemia despite the stable treatment with anti-C5 antibody.
研究概览
详细说明
About 20 PNH patients who have received eculizumab stably for at least 6 months before first dosing and still have hemoglobin (Hb) < 100 g/L will be eligible to be enrolled. All patients will take FXS6837 capsules for 24 weeks according to protocol to evaluate the efficacy and safety of FXS6837 Capsules in PNH patients who remain anemic after anti-C5 monoclonal antibody therapy. After completing the 24-week treatment, all participants who are assessed by the investigator as potentially continuing to benefit from FXS6837 may voluntarily enter a separate long-term open-label extension stud and continue to receive FXS6837 treatment.
研究类型
注册 (估计的)
阶段
- 第三阶段
联系人和位置
学习联系方式
- 姓名:Rong Fu
- 电话号码:+86 13920350233
- 邮箱:furong8369@tmu.edu.cn
研究联系人备份
- 姓名:Hui Liu
- 电话号码:+86 13821113189
- 邮箱:liuhui8003@qq.com
学习地点
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Tianjin、中国
- TianJin Medical University General Hospital
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接触:
- Hui Liu
- 电话号码:+86 13821113189
- 邮箱:liuhui8003@qq.com
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Zhejiang
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Hangzhou、Zhejiang、中国
- First Affiliated Hospital of Zhejiang University
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接触:
- Hongyan Tong
- 电话号码:+86 13958122357
- 邮箱:hongyantong@aliyun.com
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion criteria: 1. Male or female subjects aged ≥ 18 years at screening; 2. Body weight ≥ 40 kg and body mass index (BMI) ≥ 18 kg/m2 at screening; 3. Diagnosis of PNH at least 6 months before screening and confirmed by high-sensitivity flow cytometry with a PNH RBC and granulocyte/monocyte population size of ≥10% within 6 months before screening or during screening; 4. Have received a stable treatment regimen (dose and dosing interval) with anti-C5 monoclonal antibody (eculizumab) for at least 6 months prior to the first dose; 5. Have at least one blood transfusion record within 3 months before screening, or Hb level persistently < 100 g/L during stable treatment with anti-C5 monoclonal antibody within 3 months before screening (medical history data/laboratory test reports, at least 2 test records with an interval of ≥ 4 weeks); 6. Hb meeting one of the following conditions: (1) Hb concentration < 100 g/L at the first screening visit, and received RBC transfusion therapy due to PNH-related anemia during the screening period; (2) Mean Hb concentration from two measurements during the screening period < 100 g/L and all Hb measurements < 105 g/L during the screening period (these two measurements should be 2 to 6 weeks apart; multiple Hb measurements are allowed during the screening period); 7. Vaccinated against Neisseria meningitidis and Streptococcus pneumoniae before the first dose. If patients have not been previously vaccinated or need booster vaccination (according to local vaccination policies), vaccination should be completed at least 2 weeks before the first dose. If the first dose must occur within 2 weeks after vaccination, prophylactic antibiotic treatment should be used until at least 2 weeks after vaccination; 8. Participants of reproductive potential commit to having no plans for pregnancy or sperm/egg donation from screening until 1 month (female participants) or 3 months (male participants) after the last dose and voluntarily take effective physical contraceptive methods (including partners); 9. Have a detailed understanding of the nature, significance, possible benefits, potential inconveniences, and potential risks of the trial, and voluntarily participate in this clinical trial; Able to communicate well with the investigators and comply with the requirements of the entire study; Signed a written informed consent form. Exclusion criteria: 1. With laboratory evidence of bone marrow failure during screening (reticulocyte count < 100 × 109/L, or platelet count < 30 × 109/L, or neutrophil count < 0.5 × 109/L); Received acute treatment (such as platelet transfusion, granulocyte colony-stimulating factor) for thrombocytopenia or neutropenia within 30 days before screening; 2. Participants receiving other therapies before screening that have not reached the following stable treatment durations:
- Erythropoietin for at least 8 weeks
- Immunosuppressants for at least 8 weeks, systemic corticosteroids (≤ 15 mg/day) for at least 4 weeks
- Iron, vitamin B12, or folic acid supplementation for at least 4 weeks
- Anticoagulants: Vitamin K antagonists (such as warfarin) used for at least 4 weeks with a stable international normalized ratio (INR) (as determined by the investigator), low molecular weight heparin, oral anticoagulants such as aspirin, rivaroxaban, apixaban, etc., for at least 4 weeks;
- Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) for at least 8 weeks;
- Androgens for at least 4 weeks; 3. History of malignant tumors of any organ or system within 5 years before screening (except local basal cell carcinoma of the skin or carcinoma in situ of the cervix), regardless of whether treatment was received and whether there is evidence of local recurrence or metastasis; 4. History of bone marrow/hematopoietic stem cell or solid organ transplantation (such as heart, lung, kidney, liver); 5. History of splenectomy or planned surgery during the study period; 6. Subjects with significantly abnormal liver function at screening: any parameter of alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), or alkaline phosphatase (ALP) > 3 × ULN; 7. Human immunodeficiency virus (HIV) infection (HIV antibody positive), active syphilis infection, hepatitis B virus infection (hepatitis B surface antigen positive), active hepatitis C virus infection, or active tuberculosis infection at screening; 8. Concurrent systemic critical diseases, including but not limited to: advanced heart disease (such as New York Heart Association [NYHA] Class IV), severe lung disease (such as severe pulmonary hypertension [WHO class IV]), active hepatitis, severe kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 or chronic kidney disease [CKD] stage 4 or dialysis patients), unstable thrombosis, active gastrointestinal hemorrhage, other blood disorders (such as chronic anemia unrelated to PNH), which are deemed unsuitable for study participation by the investigator; 9. Known or suspected by investigators to have immunodeficiency diseases or hereditary complement deficiency; 10. History of Neisseria meningitidis infection; History of ≥ 2 episodes of pneumococcal infection; 11. Detected or suspected (as assessed by the investigator) systemic active bacterial, viral (including COVID-19), or fungal infections within 2 weeks before the first dose; Axillary temperature > 38 °C within 7 days before the first dose; 12. Suspected or known history of allergies to the IMPs or any ingredient in the IMPs; 13. Received any type of live attenuated vaccine within 4 weeks prior to screening, or plan to receive any live attenuated vaccine during the study; 14. Pregnant or lactating women or those with positive pregnancy test results; 15. Previous history of drug abuse or drug use; 16. Participated in other clinical trials of investigational drugs (or are still within 5 half-lives of the drug, whichever is longer) (except eculizumab) or medical device clinical trials within 30 days prior to screening, plans to participate in other clinical trials during the study, or having residual effects as assessed by the investigator; 17. Having diseases or medical conditions that affect drug absorption, distribution, metabolism, and excretion, or may reduce compliance or increase participant risk, such as severe gastrointestinal disease history, major gastrointestinal surgery history, swallowing difficulties, etc., as assessed by the investigator; Participants who may not be able to complete this study for other reasons, or other situations deemed unsuitable for study participation by the investigator.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的:FXS6837
100 mg FXS6837 capsule |
FXS6837 capsule will be taken orally for 24 weeks |
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Proportion of participants with hemoglobin (Hb) level ≥ 120 g/L in at least 3 of 4 measurements between Week18 and Week24 in the absence of RBC transfusion (defined as no RBC transfusion after Week2 through Week24)
大体时间:24 weeks from Baseline (Week 18 through Week 24)
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24 weeks from Baseline (Week 18 through Week 24)
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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Proportion of participants with an increase from baseline in Hb level of ≥ 20 g/L in at least 3 of 4 measurements between Week18 and Week24 in the absence of RBC transfusion (defined as no RBC transfusion after Week2 through Week24)
大体时间:24 weeks from Baseline (Baseline, Week 18 through Week 24)
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24 weeks from Baseline (Baseline, Week 18 through Week 24)
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Proportion of participants without RBC transfusion during the treatment period from between Week2 to Week24
大体时间:Week2 to Week24
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Week2 to Week24
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Change from baseline in Hb as mean of visits between Week18 and Week24
大体时间:24 weeks from Baseline (Baseline, Week 18 through Week 24)
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24 weeks from Baseline (Baseline, Week 18 through Week 24)
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Change from baseline in reticulocyte count during the treatment period from Week18 to Week24
大体时间:24 weeks from Baseline (Baseline, Week 18 through Week 24)
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24 weeks from Baseline (Baseline, Week 18 through Week 24)
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Percent change from baseline in lactate dehydrogenase (LDH) levels during the treatment period from Week18 to Week24
大体时间:24 weeks from Baseline(Baseline, Week 18 through Week 24)
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24 weeks from Baseline(Baseline, Week 18 through Week 24)
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Proportion of participants with LDH ≤ 1.5 × upper limit of normal (ULN) in at least 3 of 4 measurements between Week18 and Week24;
大体时间:24 weeks from Baseline (Week 18 through Week 24)
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24 weeks from Baseline (Week 18 through Week 24)
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Change from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) score during the treatment period from Week18 to Week24
大体时间:24 weeks from Baseline (Baseline, Week 18 through Week 24)
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24 weeks from Baseline (Baseline, Week 18 through Week 24)
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Incidence rate of BTH between Week1 and Week24
大体时间:up to 24 weeks
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up to 24 weeks
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Incidence of MAVEs between Week1 and Week24
大体时间:up to 24 weeks
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up to 24 weeks
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Safety evaluation: All participants will be observed for any adverse event (AE) during the clinical study.
大体时间:up to 24 weeks
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up to 24 weeks
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Population Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of FXS6837
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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Population Pharmacokinetics (PK): Plasma trough concentration (Ctrough) of FXS6837
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) of FXS6837
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and hemoglobin (Hb) level
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and lactate dehydrogenase (LDH) level
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and Alternative Pathway(AP) activity
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and Fragment Bb of Complement Factor B level
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and soluble C5b-9 (sC5b-9) level
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and PNH granulocyte clone percentage
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and PNH monocyte clone percentage
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and C3d+PNH red cell clone percentage
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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The exposure-response correlation between Steady-State trough Concentration (Ctrough) of FXS6837 and PNH red cell clone percentage
大体时间:From pre-dose on Day1 to Week24
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From pre-dose on Day1 to Week24
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合作者和调查者
调查人员
- 首席研究员:Rong Fu, Doctor、Tianjin Medical University General Hospital
- 首席研究员:Hongyan Tong、First Affiliated Hospital of Zhejiang University
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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